subject:(atherosclerosis caspase 1 vascular inflammation)

Temple University

1. Yin, Ying. CASPASE-1 ACTIVATION IS CRITICAL FOR ENDOTHELIAL CELL ACTIVATION, MONOCYTE MIGRATION, AND EARLY ATHEROGENESIS.

Degree: PhD, 2013, Temple University

URL: http://digital.library.temple.edu/u?/p245801coll10,252725

►

Pharmacology

Atherosclerosis, considered a chronic inflammatory disease, is the underlying mechanism for several cardiovascular diseases. Hyperlipidemia is the number one risk factor for atherogenesis. Caspase-1… (more)

▼

Pharmacology

Atherosclerosis, considered a chronic inflammatory disease, is the underlying mechanism for several cardiovascular diseases. Hyperlipidemia is the number one risk factor for atherogenesis. Caspase-1 is an inflammatory caspase, which can be activated by the metabolic stresses through pathogen associated molecular patterns (PAMPs)-recognition receptors, (PRR) recognition and inflammasome assembly. Activated caspase-1 can initiate inflammation in multiple ways. Thus, regulating inflammasome components expression is essential to control caspase-1 activation and its subsequent inflammatory processes. I hypothesized that the readiness of inflammasome component expression for caspase-1 activation in tissues is an index for inflammation privilege. Endothelial cells (EC) which are the innermost layer of the vessel and are the critical gatekeeper for monocyte migration. The first step of atherogenesis is activation of ECs, which allows monocyte adhesion and migration into the sub-endothelial layer. I also hypothesized that caspase-1 can sense hyperlipidemia and regulate EC activation and inflammation during early atherogenesis. I first determined the expression profiles of inflammasome components, pro-inflammatory caspases and PRRs is different among tissues, and cardiovascular tissues express relative less PRRs via a database-mining method. According to the readiness of inflammasome components, tissues could be classified into three tiers. The first tier consists of tissues with constitutively expressed inflammasomes. The second tier of tissues includes potentially inducible expression of one inflammasome component. The third tier of tissues has inducible expression of at least two inflammasome components. This three-tier model can be applied to determine the inflammation privilege of tissues in response to pro-inflammatory stimuli. I also demonstrated that hyperlipidemia induced caspase-1 expression and activation in aorta along with the atherogenesis in apolipoprotein E (ApoE)-/- mice with high fat (HF) diet, experimentally. We then generated the ApoE-/-/Casp-1-/- double knockout mice, and found that the ApoE-/-/Casp-1-/- mice contained significantly less atherosclerotic lesion in aortic sinus and less cytokine and chemokine expression in aortic tissues compared with ApoE-/- mice. ApoE-/-/Casp-1-/- mice also had less CD11b+/F4/80- neutrophil and CD11b+/F4/80+ monocyte recruitments into aorta compared with ApoE-/- mice. However, the percentage of monocyte subsets in peryphery blood remained at the same level in between ApoE-/- mice and ApoE-/-/Casp-1-/- mice. I then proposed that perhaps the caspase-1 activation in vascular cells, in ECs played the essential role of controling monocyte migraion. My in vitro data demonstrated that oxidized low density lipoprotein (ox-LDL) and its componnents could induced caspase-1 activation in human aortic ECs (HAECs) through ROS pathway which then led to EC activation and pyroptotic cell death. Deficiency of caspase-1 in aortic EC attenuated hyperlipidemia induced EC…

Advisors/Committee Members: Yang, Xiao-Feng, Ashby, Barrie, Autieri, Michael V., Muniswamy, Madesh, Wang, Hong, Song, Wenchao.

Subjects/Keywords: Pharmacology; atherosclerosis, caspase-1, vascular inflammation

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Yin, Y. (2013). CASPASE-1 ACTIVATION IS CRITICAL FOR ENDOTHELIAL CELL ACTIVATION, MONOCYTE MIGRATION, AND EARLY ATHEROGENESIS. (Doctoral Dissertation). Temple University. Retrieved from http://digital.library.temple.edu/u?/p245801coll10,252725

Chicago Manual of Style (16^th Edition):

Yin, Ying. “CASPASE-1 ACTIVATION IS CRITICAL FOR ENDOTHELIAL CELL ACTIVATION, MONOCYTE MIGRATION, AND EARLY ATHEROGENESIS.” 2013. Doctoral Dissertation, Temple University. Accessed April 15, 2021. http://digital.library.temple.edu/u?/p245801coll10,252725.

MLA Handbook (7^th Edition):

Yin, Ying. “CASPASE-1 ACTIVATION IS CRITICAL FOR ENDOTHELIAL CELL ACTIVATION, MONOCYTE MIGRATION, AND EARLY ATHEROGENESIS.” 2013. Web. 15 Apr 2021.

Vancouver:

Yin Y. CASPASE-1 ACTIVATION IS CRITICAL FOR ENDOTHELIAL CELL ACTIVATION, MONOCYTE MIGRATION, AND EARLY ATHEROGENESIS. [Internet] [Doctoral dissertation]. Temple University; 2013. [cited 2021 Apr 15]. Available from: http://digital.library.temple.edu/u?/p245801coll10,252725.

Council of Science Editors:

Yin Y. CASPASE-1 ACTIVATION IS CRITICAL FOR ENDOTHELIAL CELL ACTIVATION, MONOCYTE MIGRATION, AND EARLY ATHEROGENESIS. [Doctoral Dissertation]. Temple University; 2013. Available from: http://digital.library.temple.edu/u?/p245801coll10,252725

University of Cambridge

2. Morales Maldonado, Maria. Atypical Mechanisms of Synthesis, Activation and Release of Interleukin-1β from Vascular Smooth Muscle Cells.

Degree: PhD, 2020, University of Cambridge

URL: https://www.repository.cam.ac.uk/handle/1810/314916

► Atherosclerosis is a widespread disease that often leads to serious conditions such as myocardial infarction and stroke. Chronic inflammation plays an overarching role in its… (more)

▼ Atherosclerosis is a widespread disease that often leads to serious conditions such as myocardial infarction and stroke. Chronic inflammation plays an overarching role in its pathophysiology, driving initiation and progression of atherosclerosis in humans and animal models. IL-1β is a potent inflammatory cytokine implicated in atherogenesis and other vascular diseases. However, control of its activation and release has been predominantly studied in macrophages, with scant data on whether vascular smooth muscle cells (VSMCs) can release IL-1β. I investigated the expression, activation and release of IL-1β from primary human VSMCs. VSMCs expressed caspase-1, -4, and -8 under basal conditions, but not caspase-5. Stimulation of VSMCs with IL-1α and/or LPS caused rapid processing of IL-1β to the mature form, which could be detected by Western and with a mature IL-1β-specific ELISA. Although IL-1β production and cleavage was dependent on NF-κβ activation, neither caspase or NLRP3 inflammasome inhibitors prevented generation of mature IL-1β, suggesting caspase- and NLRP3-independent processing. Instead, production of mature IL-1β was blocked by the serin protease inhibitor dichloroisocoumarin, with cathepsin G the most likely enzyme responsible for pro-IL-1β activation. Interestingly, mature IL-1β was never detected in the conditioned media and instead accumulated to high levels inside VSMCs. VSMCs expressed the pore-forming protein Gasdermin D, and the active form of Gasdermin D permeabilised VSMCs, yet mature IL-1β was still not released. Finally, mature IL-1β extracted from VSMCs has 13-fold lower activity than equal amounts of mature IL-1β from Thp1 cells, however the existence of a binding partner or inhibitor of IL-1β is unlikely the cause of this phenomenon. In conclusion, the work presented in this thesis suggests that VSMCs have a novel mechanism that specifically prevents the release of active IL-1β, and that perturbation of this could potentially contribute to vascular inflammation and atherogenesis.

Subjects/Keywords: IL-1; IL-1β; Vascular Smooth Muscle Cells; Inflammation; Atherosclerosis

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Morales Maldonado, M. (2020). Atypical Mechanisms of Synthesis, Activation and Release of Interleukin-1β from Vascular Smooth Muscle Cells. (Doctoral Dissertation). University of Cambridge. Retrieved from https://www.repository.cam.ac.uk/handle/1810/314916

Chicago Manual of Style (16^th Edition):

Morales Maldonado, Maria. “Atypical Mechanisms of Synthesis, Activation and Release of Interleukin-1β from Vascular Smooth Muscle Cells.” 2020. Doctoral Dissertation, University of Cambridge. Accessed April 15, 2021. https://www.repository.cam.ac.uk/handle/1810/314916.

MLA Handbook (7^th Edition):

Morales Maldonado, Maria. “Atypical Mechanisms of Synthesis, Activation and Release of Interleukin-1β from Vascular Smooth Muscle Cells.” 2020. Web. 15 Apr 2021.

Vancouver:

Morales Maldonado M. Atypical Mechanisms of Synthesis, Activation and Release of Interleukin-1β from Vascular Smooth Muscle Cells. [Internet] [Doctoral dissertation]. University of Cambridge; 2020. [cited 2021 Apr 15]. Available from: https://www.repository.cam.ac.uk/handle/1810/314916.

Council of Science Editors:

Morales Maldonado M. Atypical Mechanisms of Synthesis, Activation and Release of Interleukin-1β from Vascular Smooth Muscle Cells. [Doctoral Dissertation]. University of Cambridge; 2020. Available from: https://www.repository.cam.ac.uk/handle/1810/314916

University of Alberta

3. Ramadan Elchames, Maison. An investigation of Crohn's Disease in the Oral Cavity.

Degree: MS, Medical Sciences-Oral Biology, 2016, University of Alberta

URL: https://era.library.ualberta.ca/files/c0k225b376

► Crohn’s disease (CD) is one of the chronic inflammatory bowel diseases (IBD) with a complex etiology involving genetic factors, priming by enteric microflora, environmental factors… (more)

▼ Crohn’s disease (CD) is one of the chronic inflammatory bowel diseases (IBD) with a complex etiology involving genetic factors, priming by enteric microflora, environmental factors and a change in the immune-mediated response, the other IBD is ulcerative colitis. The diagnosis of CD has continuously been challenging for physicians and medical practitioners as there is no single ‘‘gold standard’’ test or examination. Instead, physicians apply a combination of symptoms, clinical examination, laboratory indices, radiology, and endoscopy with histology to diagnose the disease. The techniques used for diagnostic decision are considered invasive, expensive, and time-consuming; therefore, an ideal non-invasive test is increasingly expected for initial diagnosis and identification of disease activity and the early determination of diagnosis and detection of disease activity are essential for tailoring therapy. Noninvasive specimen collection and analysis to help physicians distinguish CD would allow more rapid and appropriate treatment, as well as the potential to improve quality patient care while reducing both direct and indirect associated cost through the elimination of unnecessary procedures and more efficient medical treatment. It is well accepted that CD patients have an impaired intestinal epithelial barrier function. This allows the luminal microbiota to position themselves within close proximity of the intestinal epithelium inside the mucous layers. Furthermore, the gaps within the epithelial cell layer permit microbes to invade the intestinal tissues. This invasion triggers the dysregulated immune response characteristic of CD. Recent identification of elevated levels of caspase-1, an integral component of the inflammasome involved in pyroptosis, has been reported. In turn, this has been associated with the increased number of epithelial gaps in the epithelial layer relative to healthy controls. A systematic literature review was conducted to assess the scope and incidence of oral conditions associated with CD relative to the general population. Although hampered by a range in study designs and oral findings that were and were not reported intentionally, the results indicate that indeed CD patients have an increase in oral ulcerations, particularly aphthous ulcers. There was a loose association between the presence of these ulcers and intestinal disease activity. Next, a series of experiments were conducted to identify caspases within the oral cavity and quantify them using three study groups: healthy controls, healthy controls who had localized inflammation around the tooth scheduled for extraction, and patients with biopsy-confirmed CD who were in remission. Histology findings indicated that the CD group had more inflammation in both the lamina propria and epithelial layers compared to the two control groups. Results showed a statistically significant difference in caspase-1 densitometry between CD patients and each set of controls (p˂0.01, for each). The levels of caspase-3 (apoptosis levels) were also detected…

Subjects/Keywords: Crohn's; oral; inflammation; caspase-1

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Ramadan Elchames, M. (2016). An investigation of Crohn's Disease in the Oral Cavity. (Masters Thesis). University of Alberta. Retrieved from https://era.library.ualberta.ca/files/c0k225b376

Chicago Manual of Style (16^th Edition):

Ramadan Elchames, Maison. “An investigation of Crohn's Disease in the Oral Cavity.” 2016. Masters Thesis, University of Alberta. Accessed April 15, 2021. https://era.library.ualberta.ca/files/c0k225b376.

MLA Handbook (7^th Edition):

Ramadan Elchames, Maison. “An investigation of Crohn's Disease in the Oral Cavity.” 2016. Web. 15 Apr 2021.

Vancouver:

Ramadan Elchames M. An investigation of Crohn's Disease in the Oral Cavity. [Internet] [Masters thesis]. University of Alberta; 2016. [cited 2021 Apr 15]. Available from: https://era.library.ualberta.ca/files/c0k225b376.

Council of Science Editors:

Ramadan Elchames M. An investigation of Crohn's Disease in the Oral Cavity. [Masters Thesis]. University of Alberta; 2016. Available from: https://era.library.ualberta.ca/files/c0k225b376

University of Otago

4. Meikle, Felicity. Identifying Inflammatory Markers in Vascular Disease .

Degree: 2012, University of Otago

URL: http://hdl.handle.net/10523/2140

► Introduction: Cardiovascular disease remains the leading cause of death and disability globally. There has been much interest into the role that inflammation plays in the… (more)

▼ Introduction: Cardiovascular disease remains the leading cause of death and disability globally. There has been much interest into the role that inflammation plays in the pathogenesis of cardiovascular disease. The prominent histological feature of AAA is extensive inflammatory infiltration with T cells, B cells, macrophages, neutrophils and natural killer cells as the predominant cells involved in this inflammation. These cells produce inflammatory cytokines, which play a major role in tissue injury by inducing expression of proteolytic enzymes. In this study we have endeavoured to measure inflammatory biomarkers in patients with and without AAA and then assess which genes influence levels of these inflammatory markers. Methods: Participants included 346 with AAA and 380 vascular disease free controls. EDTA plasma samples were collected from all 726 participants and were assessed for the presence of inflammatory biomarkers using Bioplex 27 bead assay. The inflammatory biomarkers assessed included pro-inflammatory cytokines (IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-15, IL-17, IFN-γ, TNF- α), soluble receptors (IL-1RA), growth factors (G-CSF, GM-CSF, MIP-1α/β) and chemokines (IP-10, Eotaxin, MCP-1). C-reactive protein levels were determined using a specific high-sensitivity C-reactive protein (hsCRP) assay (Roche, Tina-quant high sensitivity [latex] assay). Separate genome wide association study (GWAS) was performed for IL-6, hsCRP and Eotaxin by comparing the upper with lower tertile for each marker. The genome wide data for each primary cohort participant had previously been generated using the Affymetrix SNP6.0 GeneChip® platform. Results: The important demographic predictors of AAA were identified as age, hypertension, dyslipidaemia and smoking history. Univariate analysis showed significantly elevated levels of hsCRP, IL-6, IL-8, IP-10, IL-1RA, VEGF and Eotaxin in the AAA group compared to controls (p<0.002). HsCRP, IL-6 and Eotaxin remained significantly associated with AAA within a multivariate model, which included the demographic risk factors of AAA. Within the genetic analysis those participants with high Eotaxin and hsCRP levels had 27 highly significant genes (p<1x10-4) identified, those with high IL-6 had 13 highly significant genes. These genes had associations with processes implicated in vascular disease including smooth muscle cell growth and differentiation (NRG1), apoptosis signalling (USP7, MAP2K6), cell adhesion (FLRT3), smooth muscle migration (CHN2), regulation of vascular tone (SLC28A3), and endothelial signalling and vascular function (APOLD1). Conclusion: This study replicated those associations between traditional risk factors, hsCRP, IL-6 and AAA. Eotaxin, on the other hand, has not previously been studied in relation to AAA, and thus may represent a novel indicator of AAA. Some of the most highly significant genes that were associated with elevated levels of hsCRP, IL-6 or Eotaxin had previously been noted to play a role in inflammation or vascular disease.… Advisors/Committee Members: Jones, Greg (advisor).

Subjects/Keywords: Inflammation; Vascular; Aneurysm; Atherosclerosis; ELISA

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Meikle, F. (2012). Identifying Inflammatory Markers in Vascular Disease . (Masters Thesis). University of Otago. Retrieved from http://hdl.handle.net/10523/2140

Chicago Manual of Style (16^th Edition):

Meikle, Felicity. “Identifying Inflammatory Markers in Vascular Disease .” 2012. Masters Thesis, University of Otago. Accessed April 15, 2021. http://hdl.handle.net/10523/2140.

MLA Handbook (7^th Edition):

Meikle, Felicity. “Identifying Inflammatory Markers in Vascular Disease .” 2012. Web. 15 Apr 2021.

Vancouver:

Meikle F. Identifying Inflammatory Markers in Vascular Disease . [Internet] [Masters thesis]. University of Otago; 2012. [cited 2021 Apr 15]. Available from: http://hdl.handle.net/10523/2140.

Council of Science Editors:

Meikle F. Identifying Inflammatory Markers in Vascular Disease . [Masters Thesis]. University of Otago; 2012. Available from: http://hdl.handle.net/10523/2140

5. Lucas Gonçalves Ferreira. O papel da flagelina e do sistema de secreção de Escherichia coli enteroinvasora na resposta imune inata dos macrófagos.

Degree: 2012, University of São Paulo

URL: http://www.teses.usp.br/teses/disponiveis/9/9136/tde-13122013-091247/

►

Escherichia coli enteroinvasora (EIEC) é um dos agentes etiológicos da disenteria bacilar. Seu processo fisiopatológico é desencadeado pela expressão de fatores de virulência, que proporcionam… (more)

▼

Escherichia coli enteroinvasora (EIEC) é um dos agentes etiológicos da disenteria bacilar. Seu processo fisiopatológico é desencadeado pela expressão de fatores de virulência, que proporcionam sua invasão e sobrevivência nas células do hospedeiro, ativando o sistema imune inato e adaptativo da mucosa intestinal. Trabalhos recentes têm salientado a importância do sistema de secreção e da flagelina bacteriana como agonista de receptores da imuninade inata dos macrófagos, em especial alguns dos receptores do tipo NLR. Uma vez que esta espécie de E. coli também é capaz de expressar flagelina e fazer a montagem completa do flagelo e do sistema de secreção do tipo III, a nossa proposta foi avaliar o papel da flagelina e do sistema de secreção de EIEC na resposta imune dos macrófagos murinos. Para isso, utilizamos três cepas de EIEC: a cepa selvagem; a cepa mutante no gene responsável pela síntese da flagelina; e a cepa sem o plasmídio de virulência plnv, deficiente no sistema de secreção, para a infecção de macrófagos peritoniais de camundongos C57BI/6, caspase-1-/-, IPAF-/- e ASC-/-. Neste estudo foi possível observar que o escape bacteriano e a morte dos macrófagos infectados por EIEC, assim como a ativação da caspase-1 e posterior secreção de IL-1β é independente da flagelina bacteriana, mas dependente do sistema de secreção, além disso, a ativação da caspase-1 de macrófagos infectados por EIEC é dependente do receptor IPAF e parcialmente da proteína adaptadora ASC. Assim, no nosso modelo, a ativação da caspase-1 dos macrófagos infectados por EIEC parece estar envolvida com o processamento e secreção de IL-1β e, possivelmente na secreção de IL-18, mas não na morte celular. No modelo de infecção in vivo, o sistema de secreção bacteriano foi importante para a sobrevivência bacteriana no hospedeiro, assim como para a indução de uma resposta inflamatória no local da infecção. Ainda, a caspase-1 parece ter um papel importante para o controle da infecção in vivo por EIEC, podendo assim contribuir para uma resposta imune protetora do hospedeiro.

Enteroinvasive Escherichia coli (EIEC) is one of the etiologic agents responsible for bacillary dysentery. The pathophysiological process induced by this bacteria is triggered by the expression of virulence factors that provide the invasion and survival in host cells, resulting in activation of innate and adaptive immune system present on intestinal mucosa. Recent studies have emphasized the importance of the secretion system and bacterial flagellin as agonist of innate immune receptors present in macrophage, especially NLR (Nod like receptors). Then, our proposal was evaluate the role of flagellin (f1iC) and secretion system of EIEC in the induction of immune response of murine macrophages using the EIEC strains wild type (WT), mutant flagellin gene (f1iC), and a strain deficient in secretion system (DSS) for infection of peritoneal macrophages of C57Bl/6, caspase-1-/-, IPAF-/- and ASC-/ – mice. In this study we observed that the bacterial escape and death of…

Advisors/Committee Members: Sandro Rogerio de Almeida, Marina Baquerizo Martinez, Monamaris Marques Borges, Luis Carlos de Souza Ferreira, Maria Regina D\'Imperio Lima, Joilson de Oliveira Martins.

Subjects/Keywords: Caspase-1; Escherichia coli enteroinvasora; Flagelina; Inflamação; Macrófagos; Sistema de secreção; Caspase-1; Enteroinvasive Escherichia coli; Flagellin; Inflammation; Macrophages; Secretion system

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Ferreira, L. G. (2012). O papel da flagelina e do sistema de secreção de Escherichia coli enteroinvasora na resposta imune inata dos macrófagos. (Doctoral Dissertation). University of São Paulo. Retrieved from http://www.teses.usp.br/teses/disponiveis/9/9136/tde-13122013-091247/

Chicago Manual of Style (16^th Edition):

Ferreira, Lucas Gonçalves. “O papel da flagelina e do sistema de secreção de Escherichia coli enteroinvasora na resposta imune inata dos macrófagos.” 2012. Doctoral Dissertation, University of São Paulo. Accessed April 15, 2021. http://www.teses.usp.br/teses/disponiveis/9/9136/tde-13122013-091247/.

MLA Handbook (7^th Edition):

Ferreira, Lucas Gonçalves. “O papel da flagelina e do sistema de secreção de Escherichia coli enteroinvasora na resposta imune inata dos macrófagos.” 2012. Web. 15 Apr 2021.

Vancouver:

Ferreira LG. O papel da flagelina e do sistema de secreção de Escherichia coli enteroinvasora na resposta imune inata dos macrófagos. [Internet] [Doctoral dissertation]. University of São Paulo; 2012. [cited 2021 Apr 15]. Available from: http://www.teses.usp.br/teses/disponiveis/9/9136/tde-13122013-091247/.

Council of Science Editors:

Ferreira LG. O papel da flagelina e do sistema de secreção de Escherichia coli enteroinvasora na resposta imune inata dos macrófagos. [Doctoral Dissertation]. University of São Paulo; 2012. Available from: http://www.teses.usp.br/teses/disponiveis/9/9136/tde-13122013-091247/

Temple University

6. Mai, Jietang. ROLE OF INTERLEUKIN-17 IN ENDOTHELIAL CELL ACTIVATION AND VASCULAR FUNCTION.

Degree: PhD, 2014, Temple University

URL: http://digital.library.temple.edu/u?/p245801coll10,266288

►

Pharmacology

Endothelial cell (EC) activation is a change of the endothelium from a quiescent state to one that is involved in immune reactions. Activation of… (more)

▼

Pharmacology

Endothelial cell (EC) activation is a change of the endothelium from a quiescent state to one that is involved in immune reactions. Activation of ECs is associated with the inception of atherosclerosis. Atherosclerosis is a chronic inflammatory disease that involves adaptive and innate immunity. There are many pro-inflammatory stimuli which activate the endothelium. The pro-inflammatory cytokine interleukin-17 (IL-17) has been shown to activate lung microvascular ECs. Enhanced expression of the IL-17 receptor by synovial ECs is associated with rheumatoid arthritis. These studies suggest that IL-17 plays an important role in EC biology. Nevertheless, the role of IL-17 in EC activation and endothelial dysfunction in the context of hyperlipidemia-induced atherosclerosis has not been studied. In the current study, we investigated the role of IL-17 in EC activation in vitro with mouse aortic ECs and human aortic ECs. In addition, we used the IL-17/ApoE double knock-out mouse to determine the role of IL-17 in vessel function and atherosclerosis development. First, we found that hyperlipidemia increased the number of IL-17-producing cells in the spleens from wild type mice and ApoE-/- mice that were fed a Western diet when compared to their respective normal chow diet controls. We also found that after treatment with the pro-atherogenic factor, oxidized LDL, there was an increase in the expression of IL-17 receptor by ECs. Using an EC specific array, we found that IL-17 induced significant up-regulation of four genes that are associated with EC activation in mouse aortic ECs. The four genes induced in IL-17-treated mouse aortic ECs were Cxcl1, Cxcl2, Il6, and Csf2. Moreover, we also found that IL-17 induced these four genes in human aortic ECs, and we showed that enhanced monocyte adhesion to ECs was dependent on these four genes. It was previously observed that a Western diet induced vessel dysfunction in the aortas of ApoE-/- mice. Thus, we sought to determine whether IL-17-deficiency rescues impaired endothelium-dependent relaxation in ApoE-/- mice that were fed a Western diet with the Wire Myograph System. We found that ApoE-/- mice on a 3-week Western diet had impaired endothelium-dependent relaxation when compared to IL-17-/-ApoE-/- mice. Endothelium-independent relaxation in response to sodium nitroprusside (SNP) and contraction responses induced by potassium chloride (KCl) and phenylephrine (PE) were not different in ApoE-/- mice and IL-17-/-ApoE-/- mice. Since our in vitro studies and vessel function assay pointed to a pro-atherogenic role for IL-17, we investigated lesion formation in ApoE-/- mice and IL-17-/-ApoE-/- mice. Lesion formation was assessed with Sudan IV staining of the whole aorta and Oil red O staining of aortic sinus cross sections. IL-17 deficiency in ApoE-/- mice did not affect atherosclerotic lesion formation in our study. Hyperlipidemia is a well-established risk factor for atherosclerosis so we investigated whether the pro-atherogenic role of IL-17 may have been compromised by…

Advisors/Committee Members: Yang, Xiao-Feng;, Wang, Hong, Ashby, Barrie, Autieri, Michael V., Rizzo, Victor, Sibinga, Nicholas;.

Subjects/Keywords: Immunology; Physiology; Cellular biology;

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Mai, J. (2014). ROLE OF INTERLEUKIN-17 IN ENDOTHELIAL CELL ACTIVATION AND VASCULAR FUNCTION. (Doctoral Dissertation). Temple University. Retrieved from http://digital.library.temple.edu/u?/p245801coll10,266288

Chicago Manual of Style (16^th Edition):

Mai, Jietang. “ROLE OF INTERLEUKIN-17 IN ENDOTHELIAL CELL ACTIVATION AND VASCULAR FUNCTION.” 2014. Doctoral Dissertation, Temple University. Accessed April 15, 2021. http://digital.library.temple.edu/u?/p245801coll10,266288.

MLA Handbook (7^th Edition):

Mai, Jietang. “ROLE OF INTERLEUKIN-17 IN ENDOTHELIAL CELL ACTIVATION AND VASCULAR FUNCTION.” 2014. Web. 15 Apr 2021.

Vancouver:

Mai J. ROLE OF INTERLEUKIN-17 IN ENDOTHELIAL CELL ACTIVATION AND VASCULAR FUNCTION. [Internet] [Doctoral dissertation]. Temple University; 2014. [cited 2021 Apr 15]. Available from: http://digital.library.temple.edu/u?/p245801coll10,266288.

Council of Science Editors:

Mai J. ROLE OF INTERLEUKIN-17 IN ENDOTHELIAL CELL ACTIVATION AND VASCULAR FUNCTION. [Doctoral Dissertation]. Temple University; 2014. Available from: http://digital.library.temple.edu/u?/p245801coll10,266288

University of Toronto

7. Wong, Harikesh. Crosstalk between CX3CL1 and the Cytoskeleton during Vascular Inflammation.

Degree: PhD, 2016, University of Toronto

URL: http://hdl.handle.net/1807/73195

► The ability of the cortical actin cytoskeleton to regulate the lateral diffusion of plasma membrane molecules is a fundamental guiding principle underlying many cellular processes.… (more)

▼ The ability of the cortical actin cytoskeleton to regulate the lateral diffusion of plasma membrane molecules is a fundamental guiding principle underlying many cellular processes. By creating and stabilizing diffusional barriers, the cytoskeleton can precisely regulate the association or dissociation of molecules in both time and space, ultimately dictating the signalling output of a cell. In this dissertation, I explore how modulation of the cortical actin cytoskeleton contributes to two critical aspects of vascular inflammation. Initially in Chapter 2, I focus specifically on endothelial cells and the unique transmembrane chemokine, CX3CL1, which is strongly implicated in the recruitment of leukocytes to the vascular intima and the progression of atherosclerosis. I document a novel cytoskeletal regulatory mechanism that limits the interactions between CX3CL1 and the membrane-associated protease ADAM10, thereby controlling the proteolytic release of soluble chemokine. Moreover, I discuss the implications of this mechanism in the recruitment of leukocytes during atherosclerosis, as well as the implications for membrane protease-substrate interactions in general. In Chapter 3, I explore how the proteolytically released, soluble species of CX3CL1 can subsequently influence the macrophage cytoskeleton and feed-forward to enhance the lateral diffusion and clustering of the scavenger receptor CD36. Consequently, CD36 more readily engages and internalizes cholesterol-rich, oxidized low-density lipoproteins, leading to the accumulation of cholesterol esters within macrophages, and thus, the acceleration of foam cell formation. These findings reveal a novel function of chemokines in priming macrophages for the engagement of multivalent ligand. Taken together, the body of work described in this dissertation emphasizes the role of the cytoskeleton in tuning cellular responses and demonstrates how cytoskeletal dysregulation can contribute to the progression of inflammation. Advisors/Committee Members: Robinson, Lisa, Medical Science.

Subjects/Keywords: Atherosclerosis; Cytoskeleton; Receptors; Signal integration; Single-molecule imaging; Vascular inflammation; 0379

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Wong, H. (2016). Crosstalk between CX3CL1 and the Cytoskeleton during Vascular Inflammation. (Doctoral Dissertation). University of Toronto. Retrieved from http://hdl.handle.net/1807/73195

Chicago Manual of Style (16^th Edition):

Wong, Harikesh. “Crosstalk between CX3CL1 and the Cytoskeleton during Vascular Inflammation.” 2016. Doctoral Dissertation, University of Toronto. Accessed April 15, 2021. http://hdl.handle.net/1807/73195.

MLA Handbook (7^th Edition):

Wong, Harikesh. “Crosstalk between CX3CL1 and the Cytoskeleton during Vascular Inflammation.” 2016. Web. 15 Apr 2021.

Vancouver:

Wong H. Crosstalk between CX3CL1 and the Cytoskeleton during Vascular Inflammation. [Internet] [Doctoral dissertation]. University of Toronto; 2016. [cited 2021 Apr 15]. Available from: http://hdl.handle.net/1807/73195.

Council of Science Editors:

Wong H. Crosstalk between CX3CL1 and the Cytoskeleton during Vascular Inflammation. [Doctoral Dissertation]. University of Toronto; 2016. Available from: http://hdl.handle.net/1807/73195

Uniwersytet im. Adama Mickiewicza w Poznaniu

8. Piaszyk-Borychowska, Anna. Genome-wide characterization of STAT1 and NFκB-mediated Signal Integration in Vascular Inflammation .

Degree: 2020, Uniwersytet im. Adama Mickiewicza w Poznaniu

URL: http://hdl.handle.net/10593/25464

► Atherosclerosis is a leading cause of mortality world-wide. The key etiological factor is vascular inflammation, mediated by vascular smooth muscle cells and immune cells. Signal… (more)

Subjects/Keywords: miażdżyca; zapalenie naczyń krwionośnych; interferony; atherosclerosis; vascular inflammation; interferons

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Piaszyk-Borychowska, A. (2020). Genome-wide characterization of STAT1 and NFκB-mediated Signal Integration in Vascular Inflammation . (Doctoral Dissertation). Uniwersytet im. Adama Mickiewicza w Poznaniu. Retrieved from http://hdl.handle.net/10593/25464

Chicago Manual of Style (16^th Edition):

Piaszyk-Borychowska, Anna. “Genome-wide characterization of STAT1 and NFκB-mediated Signal Integration in Vascular Inflammation .” 2020. Doctoral Dissertation, Uniwersytet im. Adama Mickiewicza w Poznaniu. Accessed April 15, 2021. http://hdl.handle.net/10593/25464.

MLA Handbook (7^th Edition):

Piaszyk-Borychowska, Anna. “Genome-wide characterization of STAT1 and NFκB-mediated Signal Integration in Vascular Inflammation .” 2020. Web. 15 Apr 2021.

Vancouver:

Piaszyk-Borychowska A. Genome-wide characterization of STAT1 and NFκB-mediated Signal Integration in Vascular Inflammation . [Internet] [Doctoral dissertation]. Uniwersytet im. Adama Mickiewicza w Poznaniu; 2020. [cited 2021 Apr 15]. Available from: http://hdl.handle.net/10593/25464.

Council of Science Editors:

Piaszyk-Borychowska A. Genome-wide characterization of STAT1 and NFκB-mediated Signal Integration in Vascular Inflammation . [Doctoral Dissertation]. Uniwersytet im. Adama Mickiewicza w Poznaniu; 2020. Available from: http://hdl.handle.net/10593/25464

University of New South Wales

9. Thai, Thuan. The role of myeloperoxidase in endothelial dysfunction.

Degree: Centre for Vascular Research, 2013, University of New South Wales

URL: http://handle.unsw.edu.au/1959.4/53224 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:11919/SOURCE02?view=true

► Endothelial dysfunction (ED) is a clinically relevant feature of cardiovascular disease (CVD), which manifests as impaired bioactivity of endothelial-derived nitric oxide (NO), produced by endothelial-NO… (more)

▼ Endothelial dysfunction (ED) is a clinically relevant feature of cardiovascular disease (CVD), which manifests as impaired bioactivity of endothelial-derived nitric oxide (NO), produced by endothelial-NO synthase (eNOS). Increasing studies implicate the pro-inflammatory enzyme myeloperoxidase (MPO) as a mediator of ED in CVD. MPO employs hydrogen peroxide (H2O2) and chloride ions to form the powerful oxidant hypochlorous acid (HOCl), and can also utilize nitrite (NO2-) or thiocyanate (SCN-) to yield nitrogen dioxide (*NO2) or hypothiocyanous acid (HOSCN), respectively. A pre-requisite for MPO-mediated ED is its sequestration in the endothelium, where it catalyses localized oxidative reactions that impact on endothelial function. This thesis investigated the implications of these oxidative reactions on eNOS activity and NO bioactivity.Incubation of endothelial cells (EC) with MPO resulted in its time-dependent accumulation into the sub-endothelium, accompanied by an intracellular re-distribution of eNOS from the plasma membrane to the cytosol. MPO-containing EC showed enhanced H2O2 consumption that coincided with the production of HOCl. In MPO-containing EC, acute exposure (0-10 min) to H2O2 induced a rapid increase in intracellular calcium (Ca2+) levels due to capacitative Ca2+ entry and this coincided with increased eNOS activity and coordinated changes to its phosphorylation at Ser-1177 and de-phosphorylation at Thr-495. Inhibition of Ca2+ and calmodulin-signalling, but not protein kinases known to phosphorylate eNOS at Ser-1177, inhibited MPO-induced eNOS phosphorylation at this site, indicating the involvement of a novel, Ca2+/calmodulin-dependent signalling pathway. Prolonged exposure (>30 min) of MPO-containing EC with H2O2 resulted in reduced cellular uptake of the eNOS substrate L-arginine, eNOS activity and protein stability, and increased production of superoxide anion radical (O2*-), events attenuated by supplementation with NO2- or SCN-. Isolated vessel studies indicated that endothelial-localized MPO impaired NO bioactivity and endothelial-dependent vasorelaxation by increasing O2*- production, which was prevented with the O2*− scavenger, polyethylene glycol O2*- dismutase, or supplementation with NO2- or SCN-. Together, these studies show that despite acutely activating eNOS, MPO-derived HOCl impairs endothelial function in a superoxide-dependent manner, which is attenuated by NO2- or SCN- supplementation. These studies provide important insights into the cell signalling and oxidative pathways by which endothelial-localized MPO promotes ED. Advisors/Committee Members: Thomas, Shane, Centre for Vascular Research, Faculty of Medicine, UNSW, Geczy, Carolyn, Centre for Infection & Inflammation Research, UNSW.

Subjects/Keywords: Nitric oxide; Endothelial function; Myeloperoxidase; Oxidative stress; Vascular inflammation; Atherosclerosis

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Thai, T. (2013). The role of myeloperoxidase in endothelial dysfunction. (Doctoral Dissertation). University of New South Wales. Retrieved from http://handle.unsw.edu.au/1959.4/53224 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:11919/SOURCE02?view=true

Chicago Manual of Style (16^th Edition):

Thai, Thuan. “The role of myeloperoxidase in endothelial dysfunction.” 2013. Doctoral Dissertation, University of New South Wales. Accessed April 15, 2021. http://handle.unsw.edu.au/1959.4/53224 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:11919/SOURCE02?view=true.

MLA Handbook (7^th Edition):

Thai, Thuan. “The role of myeloperoxidase in endothelial dysfunction.” 2013. Web. 15 Apr 2021.

Vancouver:

Thai T. The role of myeloperoxidase in endothelial dysfunction. [Internet] [Doctoral dissertation]. University of New South Wales; 2013. [cited 2021 Apr 15]. Available from: http://handle.unsw.edu.au/1959.4/53224 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:11919/SOURCE02?view=true.

Council of Science Editors:

Thai T. The role of myeloperoxidase in endothelial dysfunction. [Doctoral Dissertation]. University of New South Wales; 2013. Available from: http://handle.unsw.edu.au/1959.4/53224 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:11919/SOURCE02?view=true

10. Joffre, Jérémie. Exploration du rôle de TREM-1 dans l'athérosclérose : TREM-1 inhibition reduces atherosclerosis.

Degree: Docteur es, Biologie cellulaire, 2016, Sorbonne Paris Cité

URL: http://www.theses.fr/2016USPCB109

►

Les cellules myéloïdes jouent un rôle majeur dans le développement et les complications de l’athérosclérose. TREM (Triggering Receptor Expressed on Myeloid cells)-1 est un récepteur,… (more)

▼

Les cellules myéloïdes jouent un rôle majeur dans le développement et les complications de l’athérosclérose. TREM (Triggering Receptor Expressed on Myeloid cells)-1 est un récepteur, exprimé par les cellules myéloïdes, impliqué dans l’amplification de la réponse inflammatoire en réponse à une stimulation de la voie des TLRs. Notre objectif était d’étudier les conséquences de l’inhibition de TREM-1 sur le développement de l’athérosclérose expérimentale.Matériel et résultats : Dans un modèle de souris chimères Ldlr-/- retransplantées avec une moelle de souris Trem-1+/+ ou Trem-1-/-, nous avons montré que la déficience hématopoïétique en Trem-1 induisait une réduction de 42% de la taille des plaques d’athérosclérose au niveau du sinus aortique après 6 semaines de régime gras et une réduction de 60% après 14 semaines. De plus, la déficience hématopoïétique en Trem-1 induisait un phénotype lésionnel plus stable avec une moindre accumulation macrophagique, un centre nécrotique moins volumineux. Ces résultats ont été confirmés dans un modèle de souris ApoE-/-/Trem1-/-. Parallèlement, l’inhibition pharmacologique de TREM-1 par des injections répétées de peptide LR12 induisait une réduction significative de la taille des plaques au niveau du sinus et de l’aorte thoracique chez la souris ApoE-/- sous un régime riche en matières grasses. En utilisant différentes approches in vitro et in vivo, nous avons montré que l’invalidation génique de Trem-1 ou son inhibition pharmacologique induisait une déviation de la réponse immune vers un profil moins inflammatoire, réduisait le recrutement des monocytes non classiques dans la plaque d’athérosclérose et enfin limitait l’endocytose des lipides oxydés en régulant l’expression du CD36. Ces données de modulation de la réponse immune et de l’endocytose des lipides ont été confirmées sur des macrophages humains. Nous avons enfin montré que TREM-1 est exprimé dans des plaques d’athérosclérose humaines essentiellement par les macrophages spumeux. L’expression de TREM-1 est significativement plus importante dans les plaques athéromateuses par rapport aux plaques fibreuses. Conclusion : Nous avons montré que TREM-1 est impliqué dans le développement de l’athérosclérose à différents stades de la maladie, en modulant la réponse immune systémique et l’endocytose des lipides oxydés. L’inhibition de TREM-1 pourrait constituer une nouvelle cible thérapeutique des maladies cardiovasculaires.

Innate immune responses activated through myeloid cells contribute to the initiation, progression and complications of atherosclerosis in experimental models. However, the critical upstream pathways that link innate immune activation to foam cell formation are still poorly identified.Objectives: We hypothesized that activation of TREM (Triggering Receptor Expressed on Myeloid cells)-1 plays a determinant role in macrophage atherogenic responses. Methods and Results: Ldlr-/- mice reconstituted with bone marrow deficient for Trem-1 (Trem-1-/-) showed a strong reduction of atherosclerotic plaque size in both the…

Advisors/Committee Members: Ait-Oufella, Hafid (thesis director).

Subjects/Keywords: Athérosclérose; TREM-1; Inflammation; Macrophages; Cellules spumeuses; Atherosclerosis; TREM-1; Inflammation; Macrophage; Foam cells; 616.136

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Joffre, J. (2016). Exploration du rôle de TREM-1 dans l'athérosclérose : TREM-1 inhibition reduces atherosclerosis. (Doctoral Dissertation). Sorbonne Paris Cité. Retrieved from http://www.theses.fr/2016USPCB109

Chicago Manual of Style (16^th Edition):

Joffre, Jérémie. “Exploration du rôle de TREM-1 dans l'athérosclérose : TREM-1 inhibition reduces atherosclerosis.” 2016. Doctoral Dissertation, Sorbonne Paris Cité. Accessed April 15, 2021. http://www.theses.fr/2016USPCB109.

MLA Handbook (7^th Edition):

Joffre, Jérémie. “Exploration du rôle de TREM-1 dans l'athérosclérose : TREM-1 inhibition reduces atherosclerosis.” 2016. Web. 15 Apr 2021.

Vancouver:

Joffre J. Exploration du rôle de TREM-1 dans l'athérosclérose : TREM-1 inhibition reduces atherosclerosis. [Internet] [Doctoral dissertation]. Sorbonne Paris Cité; 2016. [cited 2021 Apr 15]. Available from: http://www.theses.fr/2016USPCB109.

Council of Science Editors:

Joffre J. Exploration du rôle de TREM-1 dans l'athérosclérose : TREM-1 inhibition reduces atherosclerosis. [Doctoral Dissertation]. Sorbonne Paris Cité; 2016. Available from: http://www.theses.fr/2016USPCB109

11. Madouri, Fahima. Asthme allergique induit par un allergène d’acarien, House Dust Mite (HDM) : rôles de la caspase-1 et de la protéine kinase C thêta (PKC-θ) : Allergic asthma induced by House Dust Mite allergen (HDM) : roles of caspase-1 and protein kinase C theta (PKC-θ).

Degree: Docteur es, Biologie des sciences du vivant. Immunologie, 2014, Université d'Orléans

URL: http://www.theses.fr/2014ORLE2055

►

Des études menées au laboratoire avaient démontré un rôle critique de l’inflammasome NLRP3 dans l’asthme allergique en réponse à l’ovalbumine en absence d’adjuvant. Mes travaux… (more)

▼

Des études menées au laboratoire avaient démontré un rôle critique de l’inflammasome NLRP3 dans l’asthme allergique en réponse à l’ovalbumine en absence d’adjuvant. Mes travaux de thèse ont porté sur le rôle de NLRP3 et de la caspase-1 dans un modèle murin d’inflammation pulmonaire induite par l’allergène d’acarien HDM. Nous avons montré un rôle régulateur de la caspase-1 dépendant de l’inflammasome NLRP3 et la molécule adaptatrice ASC mais pas de l’inflammasome NLRC4. Cette régulation de la réponse allergique se caractérise par une augmentation de l’infiltration des éosinophiles, de l’hyperréactivité bronchique et de la production des cytokines de type Th2 telles que l’IL-4, l’IL-5, l’IL-13 et l’IL-33 dans les poumons. Nous avons montré que les mécanismes responsables de cette régulation sont associés à l’IL-33 produite par les macrophages et que la neutralisation de l’IL-33 par administration locale de la protéine de fusion au récepteur ST2 (muST2-Fc) atténue les caractéristiques de l’asthme allergique. Ces résultats suggèrent que l’activation de la caspase-1 réduit la production d’IL-33 in vivo et régule ainsi la réponse l’inflammation pulmonaire induite par HDM et la réponse Th2. D’autre part, nous nous sommes intéressés au rôle de la Protéine Kinase C thêta (PKC-θ) dans ce même modèle d’inflammation pulmonaire. Nous avons démontré que PKC-θ joue non seulement un rôle protecteur dans l’asthme allergique mais également un rôle critique pour la prolifération et l’activation des cellules lymphoïdes innées (ILC2). D’autre part, l’inhibition de PKC-θ in vivo par administration orale de son inhibiteur spécifique C20 (BIX02656) atténue l’inflammation pulmonaire et la production d’IL-5 et d’IL-13. Nous suggérons que PKC-θ est impliquée dans la différenciation des Th2 et des ILC2 via un mécanisme dépendant des facteurs de transcription IRF4 et NFAT-1. Au total, mes travaux de thèse mettent en exergue deux molécules IL-33 et PKC-θ qui pourraient constituer des cibles thérapeutiques potentielles.

Studies from our laboratory have shown a critical role of NLRP3 inflammasome in response to ovalbumin allergen. In the present study we investigate the role of NLRP3 and caspase-1 in a mouse model of pulmonary inflammation induced by HDM. We have shown a regulatory role of caspase-1 dependant of the NLRP3 inflammasome and the adaptator molecule ASC but not NLRC4. The regulation of the allergic response is characterized by an increase of eosinophilia, bronchial hyperreactivity and Th2 cytokines production (IL-4, IL-5, IL-13 and IL-33) in lungs. We have shown that mechanisms responsible of this regulation are associated with IL-33 production by macrophages and that neutralization of IL-33 by local administration of a fusion protein of the ST2 receptor (muST2-Fc) reduce characteristics of asthma. These results suggest that caspase-1 activation reduce IL-33 production in vivo regulating lung inflammation and Th2 response induced by HDM. Moreover, we investigate the role of the Protein Kinase C theta (PKC-θ) in allergic airway…

Advisors/Committee Members: Ryffel, Bernhard (thesis director), Togbe Gbetchede, Dieudonnée (thesis director).

Subjects/Keywords: Inflammation pulmonaire; Asthme; HDM; NLRP3; Caspase-1; IL-33; PKC-θ; ILC2; Lung inflammation; Asthma; HDM; NLRP3; Caspase-1; IL-33; PKC-θ; ILC2; 571.96

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Madouri, F. (2014). Asthme allergique induit par un allergène d’acarien, House Dust Mite (HDM) : rôles de la caspase-1 et de la protéine kinase C thêta (PKC-θ) : Allergic asthma induced by House Dust Mite allergen (HDM) : roles of caspase-1 and protein kinase C theta (PKC-θ). (Doctoral Dissertation). Université d'Orléans. Retrieved from http://www.theses.fr/2014ORLE2055

Chicago Manual of Style (16^th Edition):

Madouri, Fahima. “Asthme allergique induit par un allergène d’acarien, House Dust Mite (HDM) : rôles de la caspase-1 et de la protéine kinase C thêta (PKC-θ) : Allergic asthma induced by House Dust Mite allergen (HDM) : roles of caspase-1 and protein kinase C theta (PKC-θ).” 2014. Doctoral Dissertation, Université d'Orléans. Accessed April 15, 2021. http://www.theses.fr/2014ORLE2055.

MLA Handbook (7^th Edition):

Madouri, Fahima. “Asthme allergique induit par un allergène d’acarien, House Dust Mite (HDM) : rôles de la caspase-1 et de la protéine kinase C thêta (PKC-θ) : Allergic asthma induced by House Dust Mite allergen (HDM) : roles of caspase-1 and protein kinase C theta (PKC-θ).” 2014. Web. 15 Apr 2021.

Vancouver:

Madouri F. Asthme allergique induit par un allergène d’acarien, House Dust Mite (HDM) : rôles de la caspase-1 et de la protéine kinase C thêta (PKC-θ) : Allergic asthma induced by House Dust Mite allergen (HDM) : roles of caspase-1 and protein kinase C theta (PKC-θ). [Internet] [Doctoral dissertation]. Université d'Orléans; 2014. [cited 2021 Apr 15]. Available from: http://www.theses.fr/2014ORLE2055.

Council of Science Editors:

Madouri F. Asthme allergique induit par un allergène d’acarien, House Dust Mite (HDM) : rôles de la caspase-1 et de la protéine kinase C thêta (PKC-θ) : Allergic asthma induced by House Dust Mite allergen (HDM) : roles of caspase-1 and protein kinase C theta (PKC-θ). [Doctoral Dissertation]. Université d'Orléans; 2014. Available from: http://www.theses.fr/2014ORLE2055

12. Wiggins, Kimberley Anne. Novel Proteases That Regulate Interleukin-1 Alpha Activity During Inflammation And Senescence.

Degree: PhD, 2018, University of Cambridge

URL: https://www.repository.cam.ac.uk/handle/1810/273664

► Interleukin-1 alpha (IL-1a) is a powerful inflammatory cytokine that modulates both innate and adaptive immunity. As such, IL-1a is implicated in the development of multiple… (more)

▼ Interleukin-1 alpha (IL-1a) is a powerful inflammatory cytokine that modulates both innate and adaptive immunity. As such, IL-1a is implicated in the development of multiple inflammatory and autoimmune diseases including atherosclerosis, arthritis and cancer. Therefore, understanding the mechanisms that regulate IL-1a activity is extremely important. For many years, pro-IL-1a was considered to be a fully active alarmin. However, we have previously shown that the removal of the pro-domain by calpain, a protease that is activated upon necrosis, significantly increases IL-1a bioactivity. The work presented in this thesis demonstrates that multiple proteases from diverse biological systems cleave and activate IL-1a. We therefore suggest that IL-1a is an important signalling hub that integrates diverse proteolytic danger signals to alert the immune system. In particular we have identified the inflammatory caspase, caspase-5, as a novel and potent activator of IL-1a. We show that caspase-5 directly cleaves pro-IL-1a during the activation of the non-canonical inflammasome by cytosolic LPS, which mimics intracellular bacterial infection. We also demonstrate that caspase-5-cleaved IL-1a mediates the senescence-associated secretory phenotype (SASP), which drives the deleterious effects of senescent cells in multiple age-related diseases. Therefore, therapeutically targeting caspase-5 may be of interest for pathologies mediated by the non-canonical inflammasome and/or senescent cells. Finally we find that rs17561, a common IL1A polymorphism, reduces active IL-1a release. We find that blood from minor allele homozygotes releases significantly less IL-1a than major allele homozygotes upon LPS stimulation. Therefore, genotyping patients under consideration for anti-IL-1a therapy could predict who would be likely to respond well to the treatment. In conclusion, the work presented in this thesis enhances our understanding of how IL-1a activity is regulated. The identification of both the caspase-5-mediated pathway of IL-1a activation and the defect conferred by the rs17561 SNP could have important clinical implications for the treatment of multiple inflammatory diseases.

Subjects/Keywords: Inflammasomes; Cytokines; IL-1; Immunity; Inflammation; Single Nucleotide Polymorphisms; Senescence; Caspase; Proteases

10 more images…

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Wiggins, K. A. (2018). Novel Proteases That Regulate Interleukin-1 Alpha Activity During Inflammation And Senescence. (Doctoral Dissertation). University of Cambridge. Retrieved from https://www.repository.cam.ac.uk/handle/1810/273664

Chicago Manual of Style (16^th Edition):

Wiggins, Kimberley Anne. “Novel Proteases That Regulate Interleukin-1 Alpha Activity During Inflammation And Senescence.” 2018. Doctoral Dissertation, University of Cambridge. Accessed April 15, 2021. https://www.repository.cam.ac.uk/handle/1810/273664.

MLA Handbook (7^th Edition):

Wiggins, Kimberley Anne. “Novel Proteases That Regulate Interleukin-1 Alpha Activity During Inflammation And Senescence.” 2018. Web. 15 Apr 2021.

Vancouver:

Wiggins KA. Novel Proteases That Regulate Interleukin-1 Alpha Activity During Inflammation And Senescence. [Internet] [Doctoral dissertation]. University of Cambridge; 2018. [cited 2021 Apr 15]. Available from: https://www.repository.cam.ac.uk/handle/1810/273664.

Council of Science Editors:

Wiggins KA. Novel Proteases That Regulate Interleukin-1 Alpha Activity During Inflammation And Senescence. [Doctoral Dissertation]. University of Cambridge; 2018. Available from: https://www.repository.cam.ac.uk/handle/1810/273664

13. BARBER, GILLIAN LOUISE. Inflammasome Involvement in Barrett's and Oesophageal Adenocarcinoma.

Degree: School of Biochemistry & Immunology. Discipline of Biochemistry, 2020, Trinity College Dublin

URL: http://hdl.handle.net/2262/92830

► Barrett's oesophagus is an inflammatory condition and a neoplastic precursor to oesophageal adenocarcinoma (OAC). Inflammasome signalling pathways contribute to acute and chronic inflammation, and can… (more)

Subjects/Keywords: Immunity; Inflammation; Obesity; Barrett's esophagus; Inflammasome; Esophageal adenocarcinoma; Caspase-1; AIM2; TLR2

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

BARBER, G. L. (2020). Inflammasome Involvement in Barrett's and Oesophageal Adenocarcinoma. (Thesis). Trinity College Dublin. Retrieved from http://hdl.handle.net/2262/92830

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

BARBER, GILLIAN LOUISE. “Inflammasome Involvement in Barrett's and Oesophageal Adenocarcinoma.” 2020. Thesis, Trinity College Dublin. Accessed April 15, 2021. http://hdl.handle.net/2262/92830.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

BARBER, GILLIAN LOUISE. “Inflammasome Involvement in Barrett's and Oesophageal Adenocarcinoma.” 2020. Web. 15 Apr 2021.

Vancouver:

BARBER GL. Inflammasome Involvement in Barrett's and Oesophageal Adenocarcinoma. [Internet] [Thesis]. Trinity College Dublin; 2020. [cited 2021 Apr 15]. Available from: http://hdl.handle.net/2262/92830.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

BARBER GL. Inflammasome Involvement in Barrett's and Oesophageal Adenocarcinoma. [Thesis]. Trinity College Dublin; 2020. Available from: http://hdl.handle.net/2262/92830

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Cambridge

14. Wiggins, Kimberley Anne. Novel proteases that regulate interleukin-1 alpha activity during inflammation and senescence.

Degree: PhD, 2018, University of Cambridge

URL: https://doi.org/10.17863/CAM.20722 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.744567

► Interleukin-1 alpha (IL-1a) is a powerful inflammatory cytokine that modulates both innate and adaptive immunity. As such, IL-1a is implicated in the development of multiple… (more)

▼ Interleukin-1 alpha (IL-1a) is a powerful inflammatory cytokine that modulates both innate and adaptive immunity. As such, IL-1a is implicated in the development of multiple inflammatory and autoimmune diseases including atherosclerosis, arthritis and cancer. Therefore, understanding the mechanisms that regulate IL-1a activity is extremely important. For many years, pro-IL-1a was considered to be a fully active alarmin. However, we have previously shown that the removal of the pro-domain by calpain, a protease that is activated upon necrosis, significantly increases IL-1a bioactivity. The work presented in this thesis demonstrates that multiple proteases from diverse biological systems cleave and activate IL-1a. We therefore suggest that IL-1a is an important signalling hub that integrates diverse proteolytic danger signals to alert the immune system. In particular we have identified the inflammatory caspase, caspase-5, as a novel and potent activator of IL-1a. We show that caspase-5 directly cleaves pro-IL-1a during the activation of the non-canonical inflammasome by cytosolic LPS, which mimics intracellular bacterial infection. We also demonstrate that caspase-5-cleaved IL-1a mediates the senescence-associated secretory phenotype (SASP), which drives the deleterious effects of senescent cells in multiple age-related diseases. Therefore, therapeutically targeting caspase-5 may be of interest for pathologies mediated by the non-canonical inflammasome and/or senescent cells. Finally we find that rs17561, a common IL1A polymorphism, reduces active IL-1a release. We find that blood from minor allele homozygotes releases significantly less IL-1a than major allele homozygotes upon LPS stimulation. Therefore, genotyping patients under consideration for anti-IL-1a therapy could predict who would be likely to respond well to the treatment. In conclusion, the work presented in this thesis enhances our understanding of how IL-1a activity is regulated. The identification of both the caspase-5-mediated pathway of IL-1a activation and the defect conferred by the rs17561 SNP could have important clinical implications for the treatment of multiple inflammatory diseases.

Subjects/Keywords: 616.07; Inflammasomes; Cytokines; IL-1; Immunity; Inflammation; Single Nucleotide Polymorphisms; Senescence; Caspase; Proteases

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Wiggins, K. A. (2018). Novel proteases that regulate interleukin-1 alpha activity during inflammation and senescence. (Doctoral Dissertation). University of Cambridge. Retrieved from https://doi.org/10.17863/CAM.20722 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.744567

Chicago Manual of Style (16^th Edition):

Wiggins, Kimberley Anne. “Novel proteases that regulate interleukin-1 alpha activity during inflammation and senescence.” 2018. Doctoral Dissertation, University of Cambridge. Accessed April 15, 2021. https://doi.org/10.17863/CAM.20722 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.744567.

MLA Handbook (7^th Edition):

Wiggins, Kimberley Anne. “Novel proteases that regulate interleukin-1 alpha activity during inflammation and senescence.” 2018. Web. 15 Apr 2021.

Vancouver:

Wiggins KA. Novel proteases that regulate interleukin-1 alpha activity during inflammation and senescence. [Internet] [Doctoral dissertation]. University of Cambridge; 2018. [cited 2021 Apr 15]. Available from: https://doi.org/10.17863/CAM.20722 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.744567.

Council of Science Editors:

Wiggins KA. Novel proteases that regulate interleukin-1 alpha activity during inflammation and senescence. [Doctoral Dissertation]. University of Cambridge; 2018. Available from: https://doi.org/10.17863/CAM.20722 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.744567

University of Ottawa

15. Zaid, Maryam. Induction of ABCA1 Expression Is Correlated With Increased CREB Phosphorylation and Altered Cytokine Secretion .

Degree: 2011, University of Ottawa

URL: http://hdl.handle.net/10393/19873

► ABCA1 is believed to affect macrophage inflammatory responses, but the mechanism by which ABCA1 may impact cytokine secretion in macrophages has yet to be fully… (more)

Subjects/Keywords: ABCA1; atherosclerosis; LXR-agonist; CREB; MKP-1; PKA; inflammation

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Zaid, M. (2011). Induction of ABCA1 Expression Is Correlated With Increased CREB Phosphorylation and Altered Cytokine Secretion . (Thesis). University of Ottawa. Retrieved from http://hdl.handle.net/10393/19873

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Zaid, Maryam. “Induction of ABCA1 Expression Is Correlated With Increased CREB Phosphorylation and Altered Cytokine Secretion .” 2011. Thesis, University of Ottawa. Accessed April 15, 2021. http://hdl.handle.net/10393/19873.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Zaid, Maryam. “Induction of ABCA1 Expression Is Correlated With Increased CREB Phosphorylation and Altered Cytokine Secretion .” 2011. Web. 15 Apr 2021.

Vancouver:

Zaid M. Induction of ABCA1 Expression Is Correlated With Increased CREB Phosphorylation and Altered Cytokine Secretion . [Internet] [Thesis]. University of Ottawa; 2011. [cited 2021 Apr 15]. Available from: http://hdl.handle.net/10393/19873.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Zaid M. Induction of ABCA1 Expression Is Correlated With Increased CREB Phosphorylation and Altered Cytokine Secretion . [Thesis]. University of Ottawa; 2011. Available from: http://hdl.handle.net/10393/19873

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Boston University

16. Krasner, Nadia Marie. Glucagon-like peptide-1 (GLP-1) and liraglutide, a synthetic GLP-1 analog, inhibit inflammation in human aortic endothelial cells via calcium and AMPK dependent mechanisms.

Degree: PhD, Medical Nutritional Sciences, 2014, Boston University

URL: http://hdl.handle.net/2144/14651

► Glucagon-like peptide-1 (GLP-1) synthetic analog therapies are prescribed for type 2 diabetes due to their effects on insulin and glucagon secretion, and glycemic control. Recent… (more)

▼ Glucagon-like peptide-1 (GLP-1) synthetic analog therapies are prescribed for type 2 diabetes due to their effects on insulin and glucagon secretion, and glycemic control. Recent studies also suggest that they may have cardiovascular benefits; however, the mechanism responsible for this is unknown. To examine this question, we evaluated the effects of GLP-1 and the GLP-1 synthetic analog, liraglutide on cell signaling and function in human aortic endothelial cells (HAECs). The results indicate that both agents inhibit TNFα and LPS induced cellular adhesion molecule expression and monocyte adhesion. They also show that incubation with 30pM GLP-1 and 100nM liraglutide stimulates an immediate increase in intracellular calcium, which activates calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ). This in turn led to a 2.5 fold increase in the phosphorylation of both AMP-activated protein kinase (AMPK) and calcium/calmodulin-dependent protein kinase 1 (CaMK1) within 5 minutes. In addition both GLP-1 and liraglutide caused a 2-fold increase in the phosphorylation of the downstream AMPK/CaMK1 targets: endothelial nitric oxide synthase (eNOS) and cAMP response element-binding protein (CREB). Inhibition of CaMKKβ with STO-609 (0.5ug/mL) blocked the phosphorylation of both AMPK and CaMK1, confirming its pivotal role. Incubation of the HAECs for three hours with lipopolysaccharide (LPS, 2ug/mL) and TNFα (10ng/mL) increased the expression of vascular cell adhesion molecule-1 (VCAM-1) and E-selectin by 5 and 2 fold, respectively. Comparable increases in THP-1 monocyte adhesion to the HAECs, a putative initiating event in atherogenesis, also occurred. Pre-incubation for one hour with either GLP-1 or liraglutide inhibited these events. Likewise, pre-incubation with the CaMKK inhibitor STO-609, or use of lentivirus shRNA to knock down AMPK, blocked the inhibitory effects of both GLP-1 and liraglutide on monocyte adhesion. These results suggest that the recently observed cardiovascular benefits of GLP-1 and liraglutide could be mediated by their effects on CaMKKβ, AMPK and CaMK1 activation, which lead to decreased adhesion molecule expression and monocyte adhesion in endothelial cells. The finding that these effects occur at concentrations of GLP-1 (30pM) and liraglutide (100nM) observed in vivo also suggests they are physiologically relevant.

Subjects/Keywords: Medicine; Atherosclerosis; Endothelial cell; GLP-1; Incretin; Inflammation; Liraglutide

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Krasner, N. M. (2014). Glucagon-like peptide-1 (GLP-1) and liraglutide, a synthetic GLP-1 analog, inhibit inflammation in human aortic endothelial cells via calcium and AMPK dependent mechanisms. (Doctoral Dissertation). Boston University. Retrieved from http://hdl.handle.net/2144/14651

Chicago Manual of Style (16^th Edition):

Krasner, Nadia Marie. “Glucagon-like peptide-1 (GLP-1) and liraglutide, a synthetic GLP-1 analog, inhibit inflammation in human aortic endothelial cells via calcium and AMPK dependent mechanisms.” 2014. Doctoral Dissertation, Boston University. Accessed April 15, 2021. http://hdl.handle.net/2144/14651.

MLA Handbook (7^th Edition):

Krasner, Nadia Marie. “Glucagon-like peptide-1 (GLP-1) and liraglutide, a synthetic GLP-1 analog, inhibit inflammation in human aortic endothelial cells via calcium and AMPK dependent mechanisms.” 2014. Web. 15 Apr 2021.

Vancouver:

Krasner NM. Glucagon-like peptide-1 (GLP-1) and liraglutide, a synthetic GLP-1 analog, inhibit inflammation in human aortic endothelial cells via calcium and AMPK dependent mechanisms. [Internet] [Doctoral dissertation]. Boston University; 2014. [cited 2021 Apr 15]. Available from: http://hdl.handle.net/2144/14651.

Council of Science Editors:

Krasner NM. Glucagon-like peptide-1 (GLP-1) and liraglutide, a synthetic GLP-1 analog, inhibit inflammation in human aortic endothelial cells via calcium and AMPK dependent mechanisms. [Doctoral Dissertation]. Boston University; 2014. Available from: http://hdl.handle.net/2144/14651

University of Cincinnati

17. Coyle, Danielle R. High Fat Diet Effects on Erythrophagocytosis and MCP-1 Levels in Mice.

Degree: MS, Allied Health Sciences: Nutrition, 2012, University of Cincinnati

URL: http://rave.ohiolink.edu/etdc/view?acc_num=ucin1353342118

► Background: Atherosclerosis, characterized by the accumulation of lipid-laden plaques in vessel walls, is a known precursor to cardiovascular disease (CVD). Oxidation of cholesterol particles… (more)

▼ Background: Atherosclerosis, characterized by the accumulation of lipid-laden plaques in vessel walls, is a known precursor to cardiovascular disease (CVD). Oxidation of cholesterol particles leads to endothelial damage and subsequent inflammation. Immune cells, such as monocytes, respond to chemokines and differentiate into macrophages, engulfing oxidized lipids, and forming foam cells within the vessel wall. Red blood cells (RBC) are known to bind chemokines through the Duffy antigen receptor for chemokines (DARC). RBCs may play a role in recruiting immune cells to lesions and contribute to the rupture of atherosclerotic plaques. Although exposure to a high fat diet (HFD) has been shown to alter RBC membrane properties, how this physiological change may affect RBC chemokine binding and macrophage interaction is less known. Objective: To determine the effects of a high fat diet on murine RBC monocyte chemoattractant protein 1 (MCP-1) content and ex vivo murine macrophage erythrophagocytosis levels. Methods: 6 week old C57BL/6 male mice were fed either chow diet (CD) as control (n=8) or a HFD (n=8) for 12 weeks. Body mass was measured upon arrival and at 18 weeks of age. Blood was collected via cardiac puncture and each sample divided into two treatments, one with heparin and one without for assessment of MCP-1 in total plasma and RBC bound. MCP-1 concentrations were measured by an ELISA for assessment of MCP-1 in total plasma and RBC bound. Erythrophagocytosis was determined ex vivo by exposing fluorescently labeled packed RBCs (pRBCs) to peritoneal macrophages harvested from C57BL/6 male mice fed a CD and measuring macrophage fluorescence. Results: The HFD mice gained more weight over the 12 weeks than the CD mice (p < 0.01). Total plasma levels of MCP-1 increased in HFD mice compared to CD mice although the difference was not significant (p = 0.149). However, RBC bound MCP-1 levels increased significantly in HFD compared to CD (p < 0.05). Macrophage erythrophagocytosis was also 43% higher among the HFD mice as compared to the CD mice (p < 0.05). Conclusion: The present study demonstrates that a high fat diet leads to increased likelihood of RBC clearance by macrophages, which could potentially contribute to inflammation. This change may be mediated by the altered RBC bound MCP-1 levels, although further work is necessary to determine cause and effect. Advisors/Committee Members: Peairs, Abigail (Committee Chair).

Subjects/Keywords: Nutrition; Inflammation; atherosclerosis; RBC; MCP-1; high fat diet; mice

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Coyle, D. R. (2012). High Fat Diet Effects on Erythrophagocytosis and MCP-1 Levels in Mice. (Masters Thesis). University of Cincinnati. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=ucin1353342118

Chicago Manual of Style (16^th Edition):

Coyle, Danielle R. “High Fat Diet Effects on Erythrophagocytosis and MCP-1 Levels in Mice.” 2012. Masters Thesis, University of Cincinnati. Accessed April 15, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1353342118.

MLA Handbook (7^th Edition):

Coyle, Danielle R. “High Fat Diet Effects on Erythrophagocytosis and MCP-1 Levels in Mice.” 2012. Web. 15 Apr 2021.

Vancouver:

Coyle DR. High Fat Diet Effects on Erythrophagocytosis and MCP-1 Levels in Mice. [Internet] [Masters thesis]. University of Cincinnati; 2012. [cited 2021 Apr 15]. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=ucin1353342118.

Council of Science Editors:

Coyle DR. High Fat Diet Effects on Erythrophagocytosis and MCP-1 Levels in Mice. [Masters Thesis]. University of Cincinnati; 2012. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=ucin1353342118

Universiteit Utrecht

18. Bouwman, J.J.M. Intracellullar infections in the pathogenesis of vascular diseases; in vitro studies.

Degree: 2009, Universiteit Utrecht

URL: http://dspace.library.uu.nl:8080/handle/1874/34997

► Various microorganisms are able to infect endothelial cells, hepatocytes, adipocytes and monocytes. Intracellular infection of these cells in vitro induces cellular dysfunction and initiates procoagulant… (more)

▼ Various microorganisms are able to infect endothelial cells, hepatocytes, adipocytes and monocytes. Intracellular infection of these cells in vitro induces cellular dysfunction and initiates procoagulant activity, hypofibrinolysis, impaired cellular function, and inflammation, as reflected by increased expression of pro-inflammatory cytokines. There was a remarkable resemblance in how monocytes, hepatocytes, endothelial cells, and adipocytes reacted to infection, with the activation of processes that could be involved in atherogenesis. This suggests that not only direct infection of the vessel wall but also indirect infection by transmission of viruses to tissues elsewhere in the body may initiate a systemic inflammatory and procoagulant state. The results of the studies presented in this thesis suggest that intracellular infections have a causal role in the etiology of vascular diseases. We propose that intracellular microorganisms should be added to the list of factors that induce endothelial dysfunction and contribute to the development of atherosclerosis. We identified inflammation, procoagulant activity, and hypofibrinolysis to be major outcomes of intracellular infection of different types of cells. Our studies identified at least some of the mechanisms by which intracellular infections may contribute to the development of cardiovascular diseases. Chronic low-grade inflammation is a component of many diseases and is often seen in atherosclerosis, obesity, diabetes and the metabolic syndrome. The presence of inflammation is evidenced by elevated plasma concentrations of a variety of markers. Atherosclerosis begins in early life and progresses to cause severe adverse effects in adult life. This is a chronic multifactorial process and cannot be explained solely in terms of the traditional cardiovascular risk factors. Infections with a variety of microorganisms during lifetime are common and could be a direct cause of atherosclerosis. Infective progeny virus may invade cells involved in atherogenesis and disseminate to other cells. Intracellular infections in vivo may become latent or even persistent, but may still be capable of having a deleterious effect on cells. The cumulative effects of simultaneous infections at various sites and/or repetitive infections may contribute to the pathogenesis and progression of atherosclerosis. Influenza virus, Cytomegalovirus (CMV), and Chlamydia pneumoniae (Cp), in particular, have been associated with cardiovascular disorders. The role of infections in endothelial injury and vascular wall inflammation has been studied extensively but current data do not allow us to determine whether infection is a cause or a co-factor in atherogenesis. Animal and pathological studies probably provide the best evidence that infections have effects in vivo similar to those seen in atherosclerosis. In the in vitro studies presented in this thesis, we investigated which of the effects caused by these infections could account for the impairment of vascular function and atherogenesis. We infected… Advisors/Committee Members: Visseren, F.L.J., Hoepelman, I.M., Diepersloot, R.J.A..

Subjects/Keywords: Geneeskunde; intracellular infection; atherosclerosis; vascular disease; inflammation; cellular dysfunction; endothelial cells; hepatocytes; monocytes; adipocytes

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Bouwman, J. J. M. (2009). Intracellullar infections in the pathogenesis of vascular diseases; in vitro studies. (Doctoral Dissertation). Universiteit Utrecht. Retrieved from http://dspace.library.uu.nl:8080/handle/1874/34997

Chicago Manual of Style (16^th Edition):

Bouwman, J J M. “Intracellullar infections in the pathogenesis of vascular diseases; in vitro studies.” 2009. Doctoral Dissertation, Universiteit Utrecht. Accessed April 15, 2021. http://dspace.library.uu.nl:8080/handle/1874/34997.

MLA Handbook (7^th Edition):

Bouwman, J J M. “Intracellullar infections in the pathogenesis of vascular diseases; in vitro studies.” 2009. Web. 15 Apr 2021.

Vancouver:

Bouwman JJM. Intracellullar infections in the pathogenesis of vascular diseases; in vitro studies. [Internet] [Doctoral dissertation]. Universiteit Utrecht; 2009. [cited 2021 Apr 15]. Available from: http://dspace.library.uu.nl:8080/handle/1874/34997.

Council of Science Editors:

Bouwman JJM. Intracellullar infections in the pathogenesis of vascular diseases; in vitro studies. [Doctoral Dissertation]. Universiteit Utrecht; 2009. Available from: http://dspace.library.uu.nl:8080/handle/1874/34997

University of Manchester

19. Yadav, Rahul. HDL FUNCTIONALITY AND LDL QUALITY: THE INFLUENCE OF OBESITY, OBSTRUCTIVE SLEEP APNOEA AND PHARMACOLOGICAL INTERVENTION.

Degree: 2013, University of Manchester

URL: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:205815

► HDL functionality and LDL quality: the influence of obesity, obstructive sleep apnoea and pharmacological interventionAims: LDL oxidation plays an important role in the initiation and… (more)

▼ HDL functionality and LDL quality: the influence of obesity, obstructive sleep apnoea and pharmacological interventionAims: LDL oxidation plays an important role in the initiation and progression of atherosclerosis. HDL impedes oxidation, glycation and glycoxidation in vitro and there is evidence to suggest paraoxonase-1 (PON1) plays an important role in this. 1. In patients with dyslipidaemia treated with statins, I assessed the relationship of serum PON1 activity with in vitro HDL antioxidant capacity, susceptibility of LDL to oxidation and the protection offered by HDL. 2. I studied the effect of the presence and severity of obstructive sleep apnoea (OSA) in morbidly obese patients on HDL anti-oxidant and anti-inflammatory functions. 3. I investigated the influence of extended release niacin/ laropiprant (ERN/LRP) versus placebo in patients who had persistent dyslipidaemia despite receiving high doses of potent statins. I assessed the effect of ERN/LRP on mediators of vascular inflammation and HDL’s in vitro anti-oxidant function.Methods: 1. LDL isolated from dyslipidemic patients was incubated with and without HDL, in the presence of Cu2+. Similarly isolated HDL was incubated alone. Lipid peroxides (LPO) generated over 3 hours were measured. Patients were divided into 2 groups based on median serum PON1 activity. 2. 41 morbidly obese patients were divided into two groups based on the presence or absence of OSA (“OSA” and “no OSA” group) or on severity of OSA (high or low apnoea-hypoapnoea index (AHI) groups). I studied HDL’s ability to protect itself from in vitro oxidation and measured serum PON1 activity, tumor necrosis factor α (TNFα) and intercellular adhesion molecule 1 (ICAM1). 3. This was a randomised double blind cross over trial, where I studied the effect of ERN/LRP compared to placebo in 27 patients who had high LDL-C inspite of maximum tolerated doses of statins. I measured lipid profile, apolipoproteins, cholesteryl ester transport protein (CETP) activity, paraoxonase 1 activity (PON1), oxidised LDL (oxLDL) and related mediators of vascular inflammation. I also examined the capacity of HDL to protect LDL from in vitro oxidation.Results and conclusion: 1. In statin treated dyslipidemic patients the capacity of HDL to protect itself and LDL from oxidation in vitro is significantly better in individuals with higher serum PON1 activity. 2. The capacity of HDL to protect itself from in vitro oxidation in morbidly obese patients is reduced with onset and severity of OSA. The differences in TNFα and ICAM1 levels may suggest endothelial dysfunction due to OSA. Oxidative damage of PON1 attributable to OSA could be a mechanism for HDL and endothelial dysfunction. 3. Treatment with ERN/LRP resulted in a significant improvement in HDL-C but did not affect HDL’s in vitro anti-oxidant function in patients who had persistent dyslipidaemia despite high doses of potent statins. For the first time I have shown that ERN/LRP reduces mediators of vascular inflammation. Advisors/Committee Members: SORAN, HANDREAN H, Heagerty, Anthony, Soran, Handrean.

Subjects/Keywords: LDL; HDL; Paraoxonase1; Oxidation; Obstructive sleep apnoea; Nicotinic acid; Laropiprant; Atherosclerosis; Vascular inflammation

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Yadav, R. (2013). HDL FUNCTIONALITY AND LDL QUALITY: THE INFLUENCE OF OBESITY, OBSTRUCTIVE SLEEP APNOEA AND PHARMACOLOGICAL INTERVENTION. (Doctoral Dissertation). University of Manchester. Retrieved from http://www.manchester.ac.uk/escholar/uk-ac-man-scw:205815

Chicago Manual of Style (16^th Edition):

Yadav, Rahul. “HDL FUNCTIONALITY AND LDL QUALITY: THE INFLUENCE OF OBESITY, OBSTRUCTIVE SLEEP APNOEA AND PHARMACOLOGICAL INTERVENTION.” 2013. Doctoral Dissertation, University of Manchester. Accessed April 15, 2021. http://www.manchester.ac.uk/escholar/uk-ac-man-scw:205815.

MLA Handbook (7^th Edition):

Yadav, Rahul. “HDL FUNCTIONALITY AND LDL QUALITY: THE INFLUENCE OF OBESITY, OBSTRUCTIVE SLEEP APNOEA AND PHARMACOLOGICAL INTERVENTION.” 2013. Web. 15 Apr 2021.

Vancouver:

Yadav R. HDL FUNCTIONALITY AND LDL QUALITY: THE INFLUENCE OF OBESITY, OBSTRUCTIVE SLEEP APNOEA AND PHARMACOLOGICAL INTERVENTION. [Internet] [Doctoral dissertation]. University of Manchester; 2013. [cited 2021 Apr 15]. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:205815.

Council of Science Editors:

Yadav R. HDL FUNCTIONALITY AND LDL QUALITY: THE INFLUENCE OF OBESITY, OBSTRUCTIVE SLEEP APNOEA AND PHARMACOLOGICAL INTERVENTION. [Doctoral Dissertation]. University of Manchester; 2013. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:205815

Universitat de Valencia

20. Gomes Marques, Patrice. Chemokine axes and inflammatory status in Metabolic Syndrome. Effect of PCSK9 inhibitors in the systemic inflammation associated to Familial Hypercholesterolemia .

Degree: 2019, Universitat de Valencia

URL: http://hdl.handle.net/10550/72833

► Metabolic syndrome (MS) is a metabolic disorder characterized by a cluster of cardiovascular risk factors and its prevalence remains increasing in Western world. It is… (more)

▼ Metabolic syndrome (MS) is a metabolic disorder characterized by a cluster of cardiovascular risk factors and its prevalence remains increasing in Western world. It is associated to low-grade systemic inflammation, a key driver of premature atherosclerosis and the major cause of cardiovascular disease (CVD). Given that CXCL16/CXCR6, CX3CL1/CX3CR1 and CCL2/CCR2 axes have been implicated in the development of CVD, we investigated the role of these axes in leukocyte adhesion to the dysfunctional arterial endothelium in a MS model. We also performed a comprehensive analysis of different cellular and soluble immune players in patients with MS. When compared with the controls, MS patients presented a CXCR6 and CX3CR1 up-regulation in platelets and several leukocytes subsets. In both groups, leukocyte adhesion to the arterial endothelium was significantly increased after TNFalpha stimulation; however, this effect was significantly higher in MS subjects than in control subjects. Notably, leukocyte adhesion was significantly reduced by the neutralization of endothelial CXCL16, CX3CL1 or CCL2 in MS patients but not in the control group. Therefore, CXCR6 or CX3CR1 expression on immune players may constitute a new membrane-associated biomarker for adverse cardiovascular events in MS. Moreover, pharmacological modulation of CXCL16/CXCR6, CX3CL1/CX3CR1 or CCL2/CCR2 chemokine axes may positively affect cardiovascular outcome in MS. Familial hypercholesterolemia (FH) is characterized by elevated plasma levels of LDL cholesterol, a result of enhanced LDL receptor (LDL-R) degradation and/or impairment of LDL-R/LDL binding. Given that proprotein convertase subtilisin/kexin type 9 (PCSK9) is involved in LDL-R degradation, during the last years, some monoclonal antibodies against human PCSK9 have been developed and demonstrated efficacy in lowering LDL plasma levels. In this study, we investigated the effect of PCSK9 silencing on endothelial dysfunction induced by TNFalpha and the impact of PCSK9 inhibitors in the systemic inflammation associated to FH. Therefore, a monoclonal antibody against PCSK9 (alirocumab) was administered for eight weeks to FH patients and different parameters were determined before and after the treatment. TNFalpha stimulation of arterial endothelial cells caused up-regulation of PCSK9. The in vitro approaches suggest that PCSK9 inhibition reduces the expression of cell adhesion molecules and membrane-bound chemokines, as well as the generation and release of soluble chemokines. Alirocumab reduced platelet and leukocyte activation, as well as CX3CR1, CXCR6 and CCR2 expression on several leukocyte subsets and decreased leukocyte adhesion in FH patients. Therefore, PCSK9 blockade might reduce endothelial dysfunction and constitute a new promising therapeutic approach in the control of FH inflammatory state, preventing further cardiovascular events in this cardiometabolic disease. Advisors/Committee Members: Sanz Ferrando, María Jesús (advisor).

Subjects/Keywords: metabolic disorders; immunopharmacology; chemokines; leukocyte-endothelium interactions; vascular inflammation; atherosclerosis; metabolic syndrome; familial hypercholesterolemia

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Gomes Marques, P. (2019). Chemokine axes and inflammatory status in Metabolic Syndrome. Effect of PCSK9 inhibitors in the systemic inflammation associated to Familial Hypercholesterolemia . (Doctoral Dissertation). Universitat de Valencia. Retrieved from http://hdl.handle.net/10550/72833

Chicago Manual of Style (16^th Edition):

Gomes Marques, Patrice. “Chemokine axes and inflammatory status in Metabolic Syndrome. Effect of PCSK9 inhibitors in the systemic inflammation associated to Familial Hypercholesterolemia .” 2019. Doctoral Dissertation, Universitat de Valencia. Accessed April 15, 2021. http://hdl.handle.net/10550/72833.

MLA Handbook (7^th Edition):

Gomes Marques, Patrice. “Chemokine axes and inflammatory status in Metabolic Syndrome. Effect of PCSK9 inhibitors in the systemic inflammation associated to Familial Hypercholesterolemia .” 2019. Web. 15 Apr 2021.

Vancouver:

Gomes Marques P. Chemokine axes and inflammatory status in Metabolic Syndrome. Effect of PCSK9 inhibitors in the systemic inflammation associated to Familial Hypercholesterolemia . [Internet] [Doctoral dissertation]. Universitat de Valencia; 2019. [cited 2021 Apr 15]. Available from: http://hdl.handle.net/10550/72833.

Council of Science Editors:

Gomes Marques P. Chemokine axes and inflammatory status in Metabolic Syndrome. Effect of PCSK9 inhibitors in the systemic inflammation associated to Familial Hypercholesterolemia . [Doctoral Dissertation]. Universitat de Valencia; 2019. Available from: http://hdl.handle.net/10550/72833

University of Manchester

21. Yadav, Rahul. HDL functionality and LDL quality : the influence of obesity, obstructive sleep apnoea and pharmacological intervention.

Degree: Thesis (M.D.), 2013, University of Manchester

URL: https://www.research.manchester.ac.uk/portal/en/theses/hdl-functionality-and-ldl-quality-the-influence-of-obesity-obstructive-sleep-apnoea-and-pharmacological-intervention(60e83156-3d19-4ccb-999c-f57ac5c6ca46).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.764257

► Aims: LDL oxidation plays an important role in the initiation and progression of atherosclerosis. HDL impedes oxidation, glycation and glycoxidation in vitro and there is… (more)

▼ Aims: LDL oxidation plays an important role in the initiation and progression of atherosclerosis. HDL impedes oxidation, glycation and glycoxidation in vitro and there is evidence to suggest paraoxonase-1 (PON1) plays an important role in this. 1. In patients with dyslipidaemia treated with statins, I assessed the relationship of serum PON1 activity with in vitro HDL antioxidant capacity, susceptibility of LDL to oxidation and the protection offered by HDL. 2. I studied the effect of the presence and severity of obstructive sleep apnoea (OSA) in morbidly obese patients on HDL anti-oxidant and anti-inflammatory functions. 3. I investigated the influence of extended release niacin/ laropiprant (ERN/LRP) versus placebo in patients who had persistent dyslipidaemia despite receiving high doses of potent statins. I assessed the effect of ERN/LRP on mediators of vascular inflammation and HDL's in vitro anti-oxidant function. Methods: 1. LDL isolated from dyslipidemic patients was incubated with and without HDL, in the presence of Cu2+. Similarly isolated HDL was incubated alone. Lipid peroxides (LPO) generated over 3 hours were measured. Patients were divided into 2 groups based on median serum PON1 activity. 2. 41 morbidly obese patients were divided into two groups based on the presence or absence of OSA ("OSA" and "no OSA" group) or on severity of OSA (high or low apnoea-hypoapnoea index (AHI) groups). I studied HDL's ability to protect itself from in vitro oxidation and measured serum PON1 activity, tumor necrosis factor alpha (TNFalpha) and intercellular adhesion molecule 1 (ICAM1). 3. This was a randomised double blind cross over trial, where I studied the effect of ERN/LRP compared to placebo in 27 patients who had high LDL-C inspite of maximum tolerated doses of statins. I measured lipid profile, apolipoproteins, cholesteryl ester transport protein (CETP) activity, paraoxonase 1 activity (PON1), oxidised LDL (oxLDL) and related mediators of vascular inflammation. I also examined the capacity of HDL to protect LDL from in vitro oxidation. Results and conclusion: 1. In statin treated dyslipidemic patients the capacity of HDL to protect itself and LDL from oxidation in vitro is significantly better in individuals with higher serum PON1 activity. 2. The capacity of HDL to protect itself from in vitro oxidation in morbidly obese patients is reduced with onset and severity of OSA. The differences in TNFalpha and ICAM1 levels may suggest endothelial dysfunction due to OSA. Oxidative damage of PON1 attributable to OSA could be a mechanism for HDL and endothelial dysfunction. 3. Treatment with ERN/LRP resulted in a significant improvement in HDL-C but did not affect HDL's in vitro anti-oxidant function in patients who had persistent dyslipidaemia despite high doses of potent statins. For the first time I have shown that ERN/LRP reduces mediators of vascular inflammation.

Subjects/Keywords: 616.1; Obstructive sleep apnoea; Vascular inflammation; Atherosclerosis; Laropiprant; Nicotinic acid; Paraoxonase1; HDL; LDL; Oxidation

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Yadav, R. (2013). HDL functionality and LDL quality : the influence of obesity, obstructive sleep apnoea and pharmacological intervention. (Doctoral Dissertation). University of Manchester. Retrieved from https://www.research.manchester.ac.uk/portal/en/theses/hdl-functionality-and-ldl-quality-the-influence-of-obesity-obstructive-sleep-apnoea-and-pharmacological-intervention(60e83156-3d19-4ccb-999c-f57ac5c6ca46).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.764257

Chicago Manual of Style (16^th Edition):

Yadav, Rahul. “HDL functionality and LDL quality : the influence of obesity, obstructive sleep apnoea and pharmacological intervention.” 2013. Doctoral Dissertation, University of Manchester. Accessed April 15, 2021. https://www.research.manchester.ac.uk/portal/en/theses/hdl-functionality-and-ldl-quality-the-influence-of-obesity-obstructive-sleep-apnoea-and-pharmacological-intervention(60e83156-3d19-4ccb-999c-f57ac5c6ca46).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.764257.

MLA Handbook (7^th Edition):

Yadav, Rahul. “HDL functionality and LDL quality : the influence of obesity, obstructive sleep apnoea and pharmacological intervention.” 2013. Web. 15 Apr 2021.

Vancouver:

Yadav R. HDL functionality and LDL quality : the influence of obesity, obstructive sleep apnoea and pharmacological intervention. [Internet] [Doctoral dissertation]. University of Manchester; 2013. [cited 2021 Apr 15]. Available from: https://www.research.manchester.ac.uk/portal/en/theses/hdl-functionality-and-ldl-quality-the-influence-of-obesity-obstructive-sleep-apnoea-and-pharmacological-intervention(60e83156-3d19-4ccb-999c-f57ac5c6ca46).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.764257.

Council of Science Editors:

Yadav R. HDL functionality and LDL quality : the influence of obesity, obstructive sleep apnoea and pharmacological intervention. [Doctoral Dissertation]. University of Manchester; 2013. Available from: https://www.research.manchester.ac.uk/portal/en/theses/hdl-functionality-and-ldl-quality-the-influence-of-obesity-obstructive-sleep-apnoea-and-pharmacological-intervention(60e83156-3d19-4ccb-999c-f57ac5c6ca46).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.764257

22. Fauteux-Daniel, Sébastien. Étude du rôle de l’inflammasome et de la kinase Styk1 dans la régulation des lymphocytes cytotoxiques : Role of the inflammasome and of Styk1 kinase in the regulation of cytotoxic lymphocytes.

Degree: Docteur es, Immunologie, 2018, Lyon

URL: http://www.theses.fr/2018LYSE1052

► Le dysfonctionnement de l'exocytose des granules cytotoxiques est responsable d'une susceptibilité accrue aux pathogènes intracellulaires qui s'accompagne de l'activation continue et anarchique des lymphocytes cytotoxiques… (more)

▼ Le dysfonctionnement de l'exocytose des granules cytotoxiques est responsable d'une susceptibilité accrue aux pathogènes intracellulaires qui s'accompagne de l'activation continue et anarchique des lymphocytes cytotoxiques et des macrophages. Ce phénomène conduit à la lymphohistiocytose hémophagocytique (HLH), un syndrome auto-inflammatoire fatal en absence d'intervention thérapeutique. Les mutations des gènes codant pour la perforine (PRF-1) ou pour certaines des protéines impliquées dans la biogénèse ou le transport vésiculaire des granules cytotoxiques sont causales des formes familiales ou primaires de la HLH (FHL). La HLH fait également partie des complications secondaires aux infections à herpesviridae et à certains désordres immunologiques importants tels que l'arthrite juvénile idiopathique (SoJIA). Au moment d'entreprendre les travaux présentés dans ce manuscrit, le premier cas de HLH induite par une mutation menant à l'activation constitutive de la composante NLRC4 de l'inflammasome était décrit. L'inflammasome est une structure multimérique composée d'un récepteur cytosolique, de la protéine échafaud ASC et de la Caspase-1. Son activation mène à la maturation des pro-formes de l'IL-1β et l'IL-18 ainsi qu'à leur sécrétion. L'activation constitutive de NLRC4 étant suffisante au déclenchement de la HLH, nous avons tenté de comprendre si cette structure y était essentielle dans le cadre des défauts génétiques de cytotoxicité. Nous avons donc invalidé la protéine ASC ou Caspase-1 dans le modèle murin de HLH déficient pour la perforine (PRF1 -/-). Nous avons également testé l'hypothèse qu'un déficit de cytotoxicité pouvait expliquer le développement de la HLH chez les patients souffrant de SoJIA. Nos résultats montrent que l'inflammasome est nécessaire à la production d'IL-18 lors de la HLH mais qu'il n'est pas essentiel au développement de la maladie dans le cadre des FHL. Par ailleurs, nous montrons que la cytotoxicité des cellules NK semble normale chez les patients atteints de SoJIA, ce qui suggère que les mécanismes immunologiques à l'origine de la HLH dans les FHL et dans les maladies autoinflammatoires comme la SoJIA sont distincts. Dans la seconde partie de ce manuscrit, nous avons étudié sur le rôle de la sérine/thréonine/tyrosine kinase Styk1 dans la régulation des lymphocytes cytotoxiques NK. Ces derniers sont responsables du contrôle immunitaire précoce des pathogènes intracellulaires et contribuent à l'immunosurveillance des cellules tumorales. Suite à leur activation, ils relâchent de très grandes quantités d'IFN-y et de TNF-α, faisant ainsi le lien entre l'immunité innée et adaptative. La reconnaissance des cellules cibles par les lymphocytes NK est gouvernée par l'expression d'un éventail de récepteurs qui transduisent des signaux, activateurs ou inhibiteurs, et dont la balance se traduit par l'activation ou la tolérance. Ces récepteurs sont codés au sein de deux complexes génétiques très denses, le complexe de cytotoxicité naturelle (NCR) et le complexe des récepteurs des leucocytes (LRC). Au… Advisors/Committee Members: Walzer, Thierry (thesis director).

Subjects/Keywords: Syndrome d’activation macrophagique; Lymphohistiocytose hémophagocytique; Auto-inflammation; Lymphocytes cytotoxiques; Perforine; Inflammasome; ASC; Caspase-1; Macrophage activation syndrome; Hemophagocytic lymphohistiocytosis; Auto-inflammatory disorders; Cytotoxic lymphocytes; Perforin; Inflammasome; ASC; Caspase-1; 571.96

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Fauteux-Daniel, S. (2018). Étude du rôle de l’inflammasome et de la kinase Styk1 dans la régulation des lymphocytes cytotoxiques : Role of the inflammasome and of Styk1 kinase in the regulation of cytotoxic lymphocytes. (Doctoral Dissertation). Lyon. Retrieved from http://www.theses.fr/2018LYSE1052

Chicago Manual of Style (16^th Edition):

Fauteux-Daniel, Sébastien. “Étude du rôle de l’inflammasome et de la kinase Styk1 dans la régulation des lymphocytes cytotoxiques : Role of the inflammasome and of Styk1 kinase in the regulation of cytotoxic lymphocytes.” 2018. Doctoral Dissertation, Lyon. Accessed April 15, 2021. http://www.theses.fr/2018LYSE1052.

MLA Handbook (7^th Edition):

Fauteux-Daniel, Sébastien. “Étude du rôle de l’inflammasome et de la kinase Styk1 dans la régulation des lymphocytes cytotoxiques : Role of the inflammasome and of Styk1 kinase in the regulation of cytotoxic lymphocytes.” 2018. Web. 15 Apr 2021.

Vancouver:

Fauteux-Daniel S. Étude du rôle de l’inflammasome et de la kinase Styk1 dans la régulation des lymphocytes cytotoxiques : Role of the inflammasome and of Styk1 kinase in the regulation of cytotoxic lymphocytes. [Internet] [Doctoral dissertation]. Lyon; 2018. [cited 2021 Apr 15]. Available from: http://www.theses.fr/2018LYSE1052.

Council of Science Editors:

Fauteux-Daniel S. Étude du rôle de l’inflammasome et de la kinase Styk1 dans la régulation des lymphocytes cytotoxiques : Role of the inflammasome and of Styk1 kinase in the regulation of cytotoxic lymphocytes. [Doctoral Dissertation]. Lyon; 2018. Available from: http://www.theses.fr/2018LYSE1052

23. Fernando Luiz Torres Gomes. Efeitos da associação de quimioterápicos na regressão de placa aterosclerótica e no perfil de marcadores inflamatórios em coelhos.

Degree: 2015, University of São Paulo

URL: http://www.teses.usp.br/teses/disponiveis/5/5131/tde-12012016-092951/

► A aterosclerose é considerada, hoje, doença inflamatória e com intensa proliferação celular, daí o racional de se usar medicamentos antiproliferativos e com ação anti-inflamatória como… (more)

▼ A aterosclerose é considerada, hoje, doença inflamatória e com intensa proliferação celular, daí o racional de se usar medicamentos antiproliferativos e com ação anti-inflamatória como o paclitaxel (PTX) e o metotrexato (MTX) no tratamento dessa condição. A nanoemulsão lipídica (LDE), de composição semelhante à da lipoproteína de baixa densidade (LDL), se liga a receptores de LDL após sua injeção endovenosa na corrente sanguínea. Como tais receptores estão superexpressos em células com altas taxas de proliferação, como ocorre no câncer e na aterosclerose, a LDE pode ser usada como veículo para direcionar agentes antiproliferativos a essas células, aumentando a sua eficácia e diminuindo a toxicidade. O paclitaxel é um quimioterápico com ação antiproliferativa usado em vários tipos de câncer e recobrindo stents farmacológicos, trabalhos anteriores, usando coelhos submetidos a uma dieta aterogênica, nos animais tratados com LDE-PTX houve redução de 60% da área lesionada. O metrotexato, além de ser usado em vários esquemas quimioterápicos, possui, também, ação anti-inflamatória, sendo usado em doenças inflamatórias crônicas, como a artrite reumatoide. Em outro estudo envolvendo, coelhos hipercolesterolêmicos, o uso de MTX comercial por 4 semanas demonstrou uma redução de 75% na área de placa aterosclerótica. Esse estudo tem por objetivo avaliar macroscopicamente a eficácia das terapias quimioterápicas combinada, composta de PTX-LDE com MTX-LDE, e monoterapia, apenas com PTX-LDE, na regressão da aterosclerose experimental. No presente trabalho, vinte e oito coelhos machos da raça New Zealand receberam dieta rica em colesterol a 1% durante 8 semanas. Depois desse período, foram divididos em quatro grupos: grupo CONTROLE, que foi sacrificado e as aortas fixadas para análise posterior, grupo DIETA, que apenas teve a ração enriquecida com colesterol a 1% suspensa, PTX, que recebeu tratamento com injeções endovenosas semanais de LDE-paclitaxel na dose de 4 mg/kg por 8 semanas, e PTX+MTX, que recebeu LDE-paclitaxel e LDE-metotrexato na dose de 4 mg/kg/semana por 8 semanas. Foram avaliados perfil hematológico, lipídico, bioquímico, ponderal e o consumo de ração. Após a eutanásia, foram medidas as lesões ateroscleróticas macroscópicas nas aortas dos coelhos. Em seguida, o arco aórtico foi analisado por morfometria e por imuno-histoquímica. Os marcadores inflamatórios foram analisados no plasma, por ELISA e por meio de expressão gênica por Qrt-pcr. Observou-se que não houve diferença no perfil ponderal e no consumo de ração entre os grupos de estudo. Não houve toxicidade hematológica, hepática e renal relacionada ao tratamento. No perfil lipídico, ao final do estudo, as concentrações de colesterol total, não HDL-C e triglicerídeos aumentaram significativamente em todos os grupos. Houve uma marcante regressão na área de placa aterosclerótica nos coelhos tratados com LDE-paclitaxel, da ordem de 64% e mais marcante no grupo LDE-metotrexato de 71%, quando comparados ao grupo CONTROLE. Na comparação com o grupo DIETA, houve, também,… Advisors/Committee Members: Carlos Vicente Serrano Junior, Paulo Sampaio Gutierrez, Rosa Ferreira dos Santos, Andrei Carvalho Spósito.

Subjects/Keywords: Aterosclerose; Coelhos; Hipercolesterolemia; Inflamação vascular; Metotrexato; Nanopartículas; Paclitaxel; Atherosclerosis; Hypercholesterolemia; Methotrexate; Nanoparticles; Paclitaxel; Rabbits; Vascular inflammation

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Gomes, F. L. T. (2015). Efeitos da associação de quimioterápicos na regressão de placa aterosclerótica e no perfil de marcadores inflamatórios em coelhos. (Doctoral Dissertation). University of São Paulo. Retrieved from http://www.teses.usp.br/teses/disponiveis/5/5131/tde-12012016-092951/

Chicago Manual of Style (16^th Edition):

Gomes, Fernando Luiz Torres. “Efeitos da associação de quimioterápicos na regressão de placa aterosclerótica e no perfil de marcadores inflamatórios em coelhos.” 2015. Doctoral Dissertation, University of São Paulo. Accessed April 15, 2021. http://www.teses.usp.br/teses/disponiveis/5/5131/tde-12012016-092951/.

MLA Handbook (7^th Edition):

Gomes, Fernando Luiz Torres. “Efeitos da associação de quimioterápicos na regressão de placa aterosclerótica e no perfil de marcadores inflamatórios em coelhos.” 2015. Web. 15 Apr 2021.

Vancouver:

Gomes FLT. Efeitos da associação de quimioterápicos na regressão de placa aterosclerótica e no perfil de marcadores inflamatórios em coelhos. [Internet] [Doctoral dissertation]. University of São Paulo; 2015. [cited 2021 Apr 15]. Available from: http://www.teses.usp.br/teses/disponiveis/5/5131/tde-12012016-092951/.

Council of Science Editors:

Gomes FLT. Efeitos da associação de quimioterápicos na regressão de placa aterosclerótica e no perfil de marcadores inflamatórios em coelhos. [Doctoral Dissertation]. University of São Paulo; 2015. Available from: http://www.teses.usp.br/teses/disponiveis/5/5131/tde-12012016-092951/

24. Chirico, Erica. Les effets de l’exercice physique sur le stress oxydant et l’inflammation dans les maladies vasculaires : The role of exercise training on oxidative stress and inflammation in vascular diseases.

Degree: Docteur es, Physiologie, 2012, Université Claude Bernard – Lyon I

URL: http://www.theses.fr/2012LYO10219

►

La drépanocytose (SCD) et l’athérosclérose sont deux maladies très diffèrentes et distinctesqui partagent les même caractéristiques. La drépanocytose est une maladie autosomalerécessive appartenant à la… (more)

▼

La drépanocytose (SCD) et l’athérosclérose sont deux maladies très diffèrentes et distinctesqui partagent les même caractéristiques. La drépanocytose est une maladie autosomalerécessive appartenant à la classe des hémoglobinopathies causée par la mutation del’hémoglobine (Hb) A en HbS. En réponse à des stress physiques tels que l’hypoxie,l’acidose, la déshydratation ou l’hyperthermie, HbS devient plus vulnérable à lapolymérisation et favorise le processus de falciformation des globules rouges. La répétitiondes cycles de polymérisation et dépolymérisation de HbS altère la forme saine desérythrocytes et conduisent aux manifestations cliniques principales de la drépanocytose:anémie, épisodes vaso-occlusifs aigus et crises hémolytiques. Il est aujourd’hui largementadmis que le stress oxydatif et l’inflammation jouent un rôle majeur dans la pathogènèse et lesconséquences physiopathologiques de la drépanocytose. L’athérosclérose, quant à elle, estune maladie inflammatoire chronique qui se caractérise par l’accumulation de plaques àl’intérieur des parois vasculaires au niveau de l’endothélium. Le stress oxydatif et la mise enjeu de phénomènes inflamatoires sont impliqués dans l’oxydation des lipides de faible densité(LDL), étape essentielle dans la pathogenèse de cette maladie.D’autre part, l’activité physique est un mécanisme important de modulation bénéfique dustress oxydatif et de l'inflammation au travers de plusieurs voies d'adaptation : l’améliorationdes enzymes antioxydantes, de la vasodilatation et des cytokines anti-inflammatoires, et labaisse des contraintes de cisaillement. Nous avons donc cherché à déterminer dans ce travailde thèse comment le contrôle du stress oxydatif et de l’inflammation par l’activité physiquepourrait réduire les complications de ces 2 pathologies (SCD et athérosclérose).

Sickle cell disease (SCD) and atherosclerosis are two very different and distinct diseases thatshare similar underlying characteristics. Sickle cell disease is a hemoglobinopathycharacterized by a genetic mutation which causes the normal blood cells to become rigid andweak. The resulting pathophysiological effects, including sickling, vaso-occlusion, andadhesion, involve the production of oxidative stress and inflammation. Atherosclerosis is achronic inflammatory disease that is characterized by plaque buildup within the vessel walls.An initial step in the pathogenesis of this disease involves the oxidation of lipids, which notonly produces inflammation, but more oxidative stress as well. We sought to determine howthe control of oxidative stress and inflammation could ameliorate complications stemmingfrom the disease.Exercise training is an important mechanism for the beneficial modulation oxidative stressand inflammation through several adaptive pathways: antioxidants, shear stress, vasodilation,and anti-inflammatory cytokines. The purpose of this thesis was to determine if thesebeneficial effects of exercise training could improve oxidative stress and consequentlyinflammation in sickle cell trait (SCT) and…

Advisors/Committee Members: Canet-Soulas, Emmanuelle (thesis director), Pialoux, Vincent (thesis director).

Subjects/Keywords: Drépanocytose; Athérosclérose; Entraînement physique; Stress oxydatif; Inflammation; Adhésion vasculaire; Sickle cell disease; Atherosclerosis; Exercise training; Oxidative stress; Inflammation; Vascular adhesion; 612.4

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Chirico, E. (2012). Les effets de l’exercice physique sur le stress oxydant et l’inflammation dans les maladies vasculaires : The role of exercise training on oxidative stress and inflammation in vascular diseases. (Doctoral Dissertation). Université Claude Bernard – Lyon I. Retrieved from http://www.theses.fr/2012LYO10219

Chicago Manual of Style (16^th Edition):

Chirico, Erica. “Les effets de l’exercice physique sur le stress oxydant et l’inflammation dans les maladies vasculaires : The role of exercise training on oxidative stress and inflammation in vascular diseases.” 2012. Doctoral Dissertation, Université Claude Bernard – Lyon I. Accessed April 15, 2021. http://www.theses.fr/2012LYO10219.

MLA Handbook (7^th Edition):

Chirico, Erica. “Les effets de l’exercice physique sur le stress oxydant et l’inflammation dans les maladies vasculaires : The role of exercise training on oxidative stress and inflammation in vascular diseases.” 2012. Web. 15 Apr 2021.

Vancouver:

Chirico E. Les effets de l’exercice physique sur le stress oxydant et l’inflammation dans les maladies vasculaires : The role of exercise training on oxidative stress and inflammation in vascular diseases. [Internet] [Doctoral dissertation]. Université Claude Bernard – Lyon I; 2012. [cited 2021 Apr 15]. Available from: http://www.theses.fr/2012LYO10219.

Council of Science Editors:

Chirico E. Les effets de l’exercice physique sur le stress oxydant et l’inflammation dans les maladies vasculaires : The role of exercise training on oxidative stress and inflammation in vascular diseases. [Doctoral Dissertation]. Université Claude Bernard – Lyon I; 2012. Available from: http://www.theses.fr/2012LYO10219

University of Manchester

25. Cobb, Christopher John. Vascular Function Prior to the Development of Overt Atherosclerosis.

Degree: 2013, University of Manchester

URL: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:213738

► Christopher John CobbUniversity of ManchesterDoctor of PhilosophyVascular function prior to the development of overt atherosclerosisSeptember 2013The formation of atherosclerotic plaques is linked to a change… (more)

▼ Christopher John CobbUniversity of ManchesterDoctor of PhilosophyVascular function prior to the development of overt atherosclerosisSeptember 2013The formation of atherosclerotic plaques is linked to a change in vascular function, with evidence of endothelial dysfunction and the proliferation of the underlying vascular smooth muscle cells (VSMCs). Prior to plaque development, risk factors are present that are capable of altering vascular function and promoting disease progression. These risk factors include hypercholesterolaemia, obesity and inflammation. The specific mechanisms of these risk factors in the early stages of atherosclerotic disease development have yet to be fully explored and are likely to be closely interwoven. The aim of this thesis was to assess the effects of these atherosclerotic risk factors, with a primary focus on the direct action of hypercholesterolaemia, on vascular function prior to the development of overt atherosclerosis.After acute ex vivo cholesterol depletion and enrichment, a range of contractile and relaxant stimuli were applied to thoracic aortic rings of wildtype C57BL/6 mice. Cholesterol depletion significantly reduced contractility to phenylephrine (p<0.05) and serotonin (p<0.01). Acute cholesterol enrichment had no effect on vascular contractility, however, acetylcholine stimulated endothelial-dependent relaxation was significantly reduced (p<0.05).Feeding with either a standard chow or a high fat ‘western’ diet was undertaken for eight weeks in both ApoE-/- and C57BL/6 mice. The extent of atherosclerotic disease development was measured through en face lipid staining and histological analysis of aortae. Atherosclerosis was present in the aortic root and intercostal branches of chow and high fat fed ApoE-/- mice but not in diet-matched C57BL/6 mice. No atherosclerotic lesions were observed in the thoracic aortae. In addition, to allow the possibility for direct associations to be made between the associated risk factors of hypercholesterolaemia, obesity and inflammation, and vascular function, a phenotypic assessment of these characteristics was conducted. Wire myography was employed to assess the vascular function of thoracic aortic rings from chow and high fat diet fed ApoE-/- mice and their age and diet matched wildtype C57BL/6 controls. It was found that contractility to both phenylephrine and serotonin was significantly increased in chow fed ApoE-/- mice (both p<0.05). Further investigation into the mechanism, using intracellular calcium imaging and the indo-1 dye, concluded that VSMC store-operated calcium entry was not altered. The exact mechanism behind this increase in contractility is therefore still unknown and there was no clear relationship to the atherosclerotic risk factors assessed. In addition to altered contractility, endothelial-dependent relaxation was shown to be significantly enhanced in high fat fed C57BL/6 (p<0.01) and ApoE-/- mice (p<0.001). Enhanced endothelial-dependent relaxations were transient and sensitive to specific inhibition of… Advisors/Committee Members: AUSTIN, CLARE CE, EISNER, DAVID DA, Austin, Clare, Eisner, David, Holt, Cathy.

Subjects/Keywords: Vascular function; Atherosclerosis

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Cobb, C. J. (2013). Vascular Function Prior to the Development of Overt Atherosclerosis. (Doctoral Dissertation). University of Manchester. Retrieved from http://www.manchester.ac.uk/escholar/uk-ac-man-scw:213738

Chicago Manual of Style (16^th Edition):

Cobb, Christopher John. “Vascular Function Prior to the Development of Overt Atherosclerosis.” 2013. Doctoral Dissertation, University of Manchester. Accessed April 15, 2021. http://www.manchester.ac.uk/escholar/uk-ac-man-scw:213738.

MLA Handbook (7^th Edition):

Cobb, Christopher John. “Vascular Function Prior to the Development of Overt Atherosclerosis.” 2013. Web. 15 Apr 2021.

Vancouver:

Cobb CJ. Vascular Function Prior to the Development of Overt Atherosclerosis. [Internet] [Doctoral dissertation]. University of Manchester; 2013. [cited 2021 Apr 15]. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:213738.

Council of Science Editors:

Cobb CJ. Vascular Function Prior to the Development of Overt Atherosclerosis. [Doctoral Dissertation]. University of Manchester; 2013. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:213738

26. Patrícia Amante de Oliveira. Indicadores inflamatórios, função endotelial e outros marcadores de risco cardíaco em pacientes idosos com sobrepeso e obesidade: resposta à suplementação de azeite de oliva, óleo de linhaça e óleo de girassol.

Degree: 2017, University of São Paulo

URL: http://www.teses.usp.br/teses/disponiveis/5/5168/tde-07082017-083438/

► A obesidade é uma doença crônica com complicações para a qual se busca o tratamento e a prevenção. A gordura visceral é um órgão endócrino… (more)

▼ A obesidade é uma doença crônica com complicações para a qual se busca o tratamento e a prevenção. A gordura visceral é um órgão endócrino de armazenamento hormonal e produtor de adipocinas inflamatórias, tornando o obeso portador de inflamação crônica, que por sua vez é uma das características da aterogênese e do envelhecimento. Os níveis aumentados de interleucina-6 e fator de necrose tumoral-alfa, citocinas multifuncionais, estão associados à morbi-mortalidade em idosos e à patogênese da aterosclerose. Nos dias atuais, a alimentação mundial é caracterizada pelo aumento do consumo de gordura saturada e gorduras trans, bem como pela redução do consumo de ácidos graxos ômega-3. O desequilíbrio na relação ômega-6/ômega-3 propicia um ambiente de inflamação crônica, sendo o estímulo inicial para doenças degenerativas. A substituição de gorduras saturadas por ácidos graxos poliinsaturados, de ácido alfa- linolênico (ALA) - ômega-3, e de ácido graxo monoinsaturado (ácido oléico - ômega- 9), parece estar associada à redução do risco de doença cardiovascular. Entre duas fontes de ácido eicosapentaenóico e ácido docosahexaenóico, os ácidos graxos ômega-3 provenientes de peixes e o ALA das fontes vegetais, este último é mais acessível financeiramente e amplamente disponível no mundo todo. Este estudo foi desenhado para avaliar comparativamente o efeito do aumento do consumo de ALA proveniente de fontes vegetais sobre os indicadores inflamatórios e a reatividade endotelial em pacientes idosos e obesos ou com sobrepeso. Foram selecionados 79 pacientes para receber doses diárias de óleo de linhaça, óleo de oliva e óleo de girassol por 12 semanas consecutivas. Foram realizadas medidas antropométricas, bioquímicas e de reatividade endotelial antes e após a intervenção, sem nenhuma modificação na dieta dos participantes ou em suas medicações utilizadas, não havendo mudanças antropométricas após a conclusão do estudo. Houve melhora em alguns parâmetros bioquímicos com o óleo de linhaça, que reduziu os níveis de PCRus, C3, C4 e fibrinogênio; com o óleo de girassol, que reduziu os níveis de leptina, ApoB e também a relação Apo B/ApoA1; e com o óleo de oliva que beneficiou a relação Apo B/ApoA1 e os níveis de C4. A espessura da artéria carótida também teve melhora significativa com os três óleos suplementados, mais acentuada com o óleo de linhaça e o óleo de oliva. Além disto, o óleo de girassol melhorou significativamente a distensibilidade da parede arterial e da vasodilatação fluxo-mediada (VFM) e o óleo de oliva apresentou tendência de melhora na VFM. Concluímos que a suplementação de ácidos graxos insaturados provenientes dos três óleos vegetais atenuou o quadro pró-inflamatório e pró-trombótico. Ocorreu melhora do perfil de marcadores bioquímicos e resultados significativos estatisticamente nos marcadores de reatividade endotelial como redução da espessura da íntima-média da artéria carótida, melhora da distensibilidade da parede arterial e melhora da funcionalidade medida pela VFM. Foi benéfica sua introdução à dieta, a fim de… Advisors/Committee Members: Joel Faintuch, José Jukemura, Carlos Alberto Malheiros, Mohamed Hassan Saleh.

Subjects/Keywords: Ácidos graxos insaturados; Aterosclerose; Endotélio vascular; Espessura íntima-média carotídea; Idoso; Inflamação; Obesidade; Rigidez vascular; Aged; Atherosclerosis; Carotid intima-media thickness; Endothelium vascular; Fatty acids unsaturated; Inflammation; Obesity; Vascular stiffness

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Oliveira, P. A. d. (2017). Indicadores inflamatórios, função endotelial e outros marcadores de risco cardíaco em pacientes idosos com sobrepeso e obesidade: resposta à suplementação de azeite de oliva, óleo de linhaça e óleo de girassol. (Doctoral Dissertation). University of São Paulo. Retrieved from http://www.teses.usp.br/teses/disponiveis/5/5168/tde-07082017-083438/

Chicago Manual of Style (16^th Edition):

Oliveira, Patrícia Amante de. “Indicadores inflamatórios, função endotelial e outros marcadores de risco cardíaco em pacientes idosos com sobrepeso e obesidade: resposta à suplementação de azeite de oliva, óleo de linhaça e óleo de girassol.” 2017. Doctoral Dissertation, University of São Paulo. Accessed April 15, 2021. http://www.teses.usp.br/teses/disponiveis/5/5168/tde-07082017-083438/.

MLA Handbook (7^th Edition):

Oliveira, Patrícia Amante de. “Indicadores inflamatórios, função endotelial e outros marcadores de risco cardíaco em pacientes idosos com sobrepeso e obesidade: resposta à suplementação de azeite de oliva, óleo de linhaça e óleo de girassol.” 2017. Web. 15 Apr 2021.

Vancouver:

Oliveira PAd. Indicadores inflamatórios, função endotelial e outros marcadores de risco cardíaco em pacientes idosos com sobrepeso e obesidade: resposta à suplementação de azeite de oliva, óleo de linhaça e óleo de girassol. [Internet] [Doctoral dissertation]. University of São Paulo; 2017. [cited 2021 Apr 15]. Available from: http://www.teses.usp.br/teses/disponiveis/5/5168/tde-07082017-083438/.

Council of Science Editors:

Oliveira PAd. Indicadores inflamatórios, função endotelial e outros marcadores de risco cardíaco em pacientes idosos com sobrepeso e obesidade: resposta à suplementação de azeite de oliva, óleo de linhaça e óleo de girassol. [Doctoral Dissertation]. University of São Paulo; 2017. Available from: http://www.teses.usp.br/teses/disponiveis/5/5168/tde-07082017-083438/

Temple University

27. Sommerville, Laura Jean. The Role of Allograft Inflammatory Factor-1 in Vascular Smooth Muscle Cell Activation and Development of Vascular Proliferative Disease.

Degree: PhD, 2010, Temple University

URL: http://digital.library.temple.edu/u?/p245801coll10,76756

►

Molecular and Cellular Physiology

The underlying cause of all vascular proliferative diseases is injury-induced activation of vascular endothelium and vascular smooth muscle cells (VSMC). Activated… (more)

▼

Molecular and Cellular Physiology

The underlying cause of all vascular proliferative diseases is injury-induced activation of vascular endothelium and vascular smooth muscle cells (VSMC). Activated VSMC proliferate, than migrate from the arterial media to the intima, contributing to neointima formation. Activated immune cells, vascular cells, and their endogenous regulators mediate this complex process. One integral regulator of VSMC activation is allograft inflammatory factor-1 (AIF-1). AIF-1 is a cytoplasmic scaffold protein, expressed constitutively in lymphoid cells and induced in VSMC by injury. Stable over expression of AIF-1 increases VSMC proliferation and migration in vitro, causes increased injury-induced neointima formation, and increases Rac1 and p38 MAP Kinase activity. Recent studies show a correlation between VSMC expression of AIF-1 and atherosclerosis development. We hypothesize that VSMC over expression of AIF-1 contributes to atherosclerosis development by increasing activity of inflammatory signaling molecules, and that inhibiting VSMC AIF-1 expression will decrease injury-induced neointima formation. Rat carotid arteries transfected with AIF-1 si RNA adenovirus after balloon angioplasty developed significantly less neointima compared to controls. AIF-1 si RNA transfected VSMC proliferated significantly less than AIF-1 or GFP transfected VSMC, while AIF-1 si RNA transfection did not attenuate AIF-1-mediated migration. p38 inhibition showed that AIF-1-mediated proliferation is dependent on p38 activation while AIF-1-mediated migration is not. AIF-1 transgenic mice fed a high fat diet showed significantly more atherosclerotic lesions than WT littermates. Boyden Chamber assays showed OxLDL treatment increases VSMC migration but does not effect AIF-1-mediated migration. Expression of migration and inflammatory responsive genes in AIF-1 and XGal transfected VSMC after OxLDL treatment at various time points were examined. MMP-2 and -9 expression did not change. ICAM-1 and VCAM-1 expression increased in both groups. AIF-1 VSMC showed significantly higher ICAM-1 expression at baseline and early time points and elevated, but not significantly higher VCAM-1 expression at early time points. Western blots showed increased activation of NF-kB in AIF-1 transfected VSMC at baseline and 30 minutes after OxLDL stimulation compared to XGal transfected VSMC. Expression of the scavenger receptor receptors CD36 and SRA(I) expression increased after lipid treatment in AIF-1 and XGal transfected groups. AIF-1 VSMC showed sustained expression of both receptors after 16 hours of treatment compared to XGal VSMC, which showed decreased expression at that time point. CXCL16/PSOX expression increased with treatment, but differences in expression patterns were not seen between cell groups. Analysis showed significantly more OxLDL was taken up by AIF-1 VSMC compared to XGal VSMC. These data show that AIF-1 expression in VSMC is tightly linked to the vascular response to injury and development of vascular disease. Although…

Advisors/Committee Members: Autieri, Michael V., Driska, Steven Paul, Houser, Steven R., Ganea, Doina, Wolfson, Marla R..

Subjects/Keywords: Biology, Physiology; Allograft Inflammatory Factor-1; Atherosclerosis; Smooth Muscle Cell Activation; Vascular Proliferative Disease

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Sommerville, L. J. (2010). The Role of Allograft Inflammatory Factor-1 in Vascular Smooth Muscle Cell Activation and Development of Vascular Proliferative Disease. (Doctoral Dissertation). Temple University. Retrieved from http://digital.library.temple.edu/u?/p245801coll10,76756

Chicago Manual of Style (16^th Edition):

Sommerville, Laura Jean. “The Role of Allograft Inflammatory Factor-1 in Vascular Smooth Muscle Cell Activation and Development of Vascular Proliferative Disease.” 2010. Doctoral Dissertation, Temple University. Accessed April 15, 2021. http://digital.library.temple.edu/u?/p245801coll10,76756.

MLA Handbook (7^th Edition):

Sommerville, Laura Jean. “The Role of Allograft Inflammatory Factor-1 in Vascular Smooth Muscle Cell Activation and Development of Vascular Proliferative Disease.” 2010. Web. 15 Apr 2021.

Vancouver:

Sommerville LJ. The Role of Allograft Inflammatory Factor-1 in Vascular Smooth Muscle Cell Activation and Development of Vascular Proliferative Disease. [Internet] [Doctoral dissertation]. Temple University; 2010. [cited 2021 Apr 15]. Available from: http://digital.library.temple.edu/u?/p245801coll10,76756.

Council of Science Editors:

Sommerville LJ. The Role of Allograft Inflammatory Factor-1 in Vascular Smooth Muscle Cell Activation and Development of Vascular Proliferative Disease. [Doctoral Dissertation]. Temple University; 2010. Available from: http://digital.library.temple.edu/u?/p245801coll10,76756

28. Walker, Rachel Elizabeth. Perivascular adipose tissue and vascular function: the influence of nitric oxide, ageing and atherosclerosis.

Degree: 2017, University of Manchester

URL: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:307139

► Background: The incidence of coronary heart diseases, including atherosclerosis, increases with ageing. The factors which influence arterial function, and which may be changed with ageing,… (more)

Subjects/Keywords: Perivascular adipose tissue; ApoE; Caveolin-1; Ageing; Nitric oxide; Aorta; Atherosclerosis; Vascular function

12 more images…

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Walker, R. E. (2017). Perivascular adipose tissue and vascular function: the influence of nitric oxide, ageing and atherosclerosis. (Doctoral Dissertation). University of Manchester. Retrieved from http://www.manchester.ac.uk/escholar/uk-ac-man-scw:307139

Chicago Manual of Style (16^th Edition):

Walker, Rachel Elizabeth. “Perivascular adipose tissue and vascular function: the influence of nitric oxide, ageing and atherosclerosis.” 2017. Doctoral Dissertation, University of Manchester. Accessed April 15, 2021. http://www.manchester.ac.uk/escholar/uk-ac-man-scw:307139.

MLA Handbook (7^th Edition):

Walker, Rachel Elizabeth. “Perivascular adipose tissue and vascular function: the influence of nitric oxide, ageing and atherosclerosis.” 2017. Web. 15 Apr 2021.

Vancouver:

Walker RE. Perivascular adipose tissue and vascular function: the influence of nitric oxide, ageing and atherosclerosis. [Internet] [Doctoral dissertation]. University of Manchester; 2017. [cited 2021 Apr 15]. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:307139.

Council of Science Editors:

Walker RE. Perivascular adipose tissue and vascular function: the influence of nitric oxide, ageing and atherosclerosis. [Doctoral Dissertation]. University of Manchester; 2017. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:307139

29. Walker, Rachel. Perivascular adipose tissue and vascular function : the influence of nitric oxide, ageing and atherosclerosis.

Degree: PhD, 2017, University of Manchester

URL: https://www.research.manchester.ac.uk/portal/en/theses/perivascular-adipose-tissue-and-vascular-function-the-influence-of-nitric-oxide-ageing-and-atherosclerosis(ea89f957-1a84-423a-b99b-5b180ea6874d).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.764574

► Background: The incidence of coronary heart diseases, including atherosclerosis, increases with ageing. The factors which influence arterial function, and which may be changed with ageing,… (more)

Subjects/Keywords: 616.1; Aorta; Vascular function; Nitric oxide; Atherosclerosis; Caveolin-1; ApoE; Perivascular adipose tissue; Ageing

12 more images…

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Walker, R. (2017). Perivascular adipose tissue and vascular function : the influence of nitric oxide, ageing and atherosclerosis. (Doctoral Dissertation). University of Manchester. Retrieved from https://www.research.manchester.ac.uk/portal/en/theses/perivascular-adipose-tissue-and-vascular-function-the-influence-of-nitric-oxide-ageing-and-atherosclerosis(ea89f957-1a84-423a-b99b-5b180ea6874d).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.764574

Chicago Manual of Style (16^th Edition):

Walker, Rachel. “Perivascular adipose tissue and vascular function : the influence of nitric oxide, ageing and atherosclerosis.” 2017. Doctoral Dissertation, University of Manchester. Accessed April 15, 2021. https://www.research.manchester.ac.uk/portal/en/theses/perivascular-adipose-tissue-and-vascular-function-the-influence-of-nitric-oxide-ageing-and-atherosclerosis(ea89f957-1a84-423a-b99b-5b180ea6874d).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.764574.

MLA Handbook (7^th Edition):

Walker, Rachel. “Perivascular adipose tissue and vascular function : the influence of nitric oxide, ageing and atherosclerosis.” 2017. Web. 15 Apr 2021.

Vancouver:

Walker R. Perivascular adipose tissue and vascular function : the influence of nitric oxide, ageing and atherosclerosis. [Internet] [Doctoral dissertation]. University of Manchester; 2017. [cited 2021 Apr 15]. Available from: https://www.research.manchester.ac.uk/portal/en/theses/perivascular-adipose-tissue-and-vascular-function-the-influence-of-nitric-oxide-ageing-and-atherosclerosis(ea89f957-1a84-423a-b99b-5b180ea6874d).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.764574.

Council of Science Editors:

Walker R. Perivascular adipose tissue and vascular function : the influence of nitric oxide, ageing and atherosclerosis. [Doctoral Dissertation]. University of Manchester; 2017. Available from: https://www.research.manchester.ac.uk/portal/en/theses/perivascular-adipose-tissue-and-vascular-function-the-influence-of-nitric-oxide-ageing-and-atherosclerosis(ea89f957-1a84-423a-b99b-5b180ea6874d).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.764574

Université de Sherbrooke

30. Sikpa, Dina. L’inflammation : son rôle dans la formation des métastases cérébrales, et les complications liées à la radiothérapie dans leur prise en charge: Inflammation, its role in brain metastases formation, and radio-induced complications in their management.

Degree: 2020, Université de Sherbrooke

URL: http://hdl.handle.net/11143/17022

► Abstract: The occurrence of brain metastases (BM) increases in many types of cancer and represents a significant challenge for the management of patient treatment. Inflammation… (more)

▼ Abstract: The occurrence of brain metastases (BM) increases in many types of cancer and represents a significant challenge for the management of patient treatment. Inflammation is central to the development of cancer. While an intra-tumoral inflammatory microenvironment contributes to the acquisition of malignant phenotypes, inflammation at secondary distant sites facilitates the adhesion of circulating tumor cells to the activated vascular endothelium and the consequent formation of metastases. Stereotactic radiosurgery (SRS) is commonly used to treat metastatic brain tumors. However, the surrounding healthy brain tissue receives a significant dose of radiation resulting in early and late side effects such as radiation necrosis (RN) and neurocognitive deficits which reduces treatment benefits and patient’s quality of life. The pathogenesis of delayed RN is of growing interest, and a number of studies supports a significant role for inflammation. Here, the purpose of this thesis is to better understand how cerebrovascular inflammation influences the cerebral environment and leads to the development of cerebral pathologies, in this case, BM and the delayed RN. We therefore have developed animal models and used multimodal imaging for the study of these events. We first studied the effect of inflammation on BM implantation. By using molecular imaging and machine learning, we showed that the metastatic burden increases in an inflammatory context. Blocking the Vascular Cell Adhesion Molecule -1 (VCAM-1) mitigates that effect. Then, for the characterization of molecular and cellular biomarkers of the delayed RN as a result of SRS-induced inflammation, using MR imaging of VCAM-1 enabled the detection of cerebrovascular inflammation preceding the formation of the necrotic core. Our results suggest that adhesion molecules expressed at the surface of activated endothelial cells, particularly VCAM-1, play a crucial role in BM formation and potentially the development of delayed RN. Advisors/Committee Members: Lepage, Martin (advisor), Gobeil, Fernand Jr (advisor).

Subjects/Keywords: Métastases Cérébrales; Inflammation; Inflammation Cérébro-Vasculaire; Radionécrose; Molécules d’Adhésion; Protéine d’Adhésion Vasculaire Cellulaire-1; Brain Metastases; Inflammation; Cerebrovascular Inflammation; Radionecrosis; Vascular Cell Adhesion Molecule -1 (VCAM-1)

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Sikpa, D. (2020). L’inflammation : son rôle dans la formation des métastases cérébrales, et les complications liées à la radiothérapie dans leur prise en charge: Inflammation, its role in brain metastases formation, and radio-induced complications in their management. (Doctoral Dissertation). Université de Sherbrooke. Retrieved from http://hdl.handle.net/11143/17022

Chicago Manual of Style (16^th Edition):

Sikpa, Dina. “L’inflammation : son rôle dans la formation des métastases cérébrales, et les complications liées à la radiothérapie dans leur prise en charge: Inflammation, its role in brain metastases formation, and radio-induced complications in their management.” 2020. Doctoral Dissertation, Université de Sherbrooke. Accessed April 15, 2021. http://hdl.handle.net/11143/17022.

MLA Handbook (7^th Edition):

Sikpa, Dina. “L’inflammation : son rôle dans la formation des métastases cérébrales, et les complications liées à la radiothérapie dans leur prise en charge: Inflammation, its role in brain metastases formation, and radio-induced complications in their management.” 2020. Web. 15 Apr 2021.

Vancouver:

Sikpa D. L’inflammation : son rôle dans la formation des métastases cérébrales, et les complications liées à la radiothérapie dans leur prise en charge: Inflammation, its role in brain metastases formation, and radio-induced complications in their management. [Internet] [Doctoral dissertation]. Université de Sherbrooke; 2020. [cited 2021 Apr 15]. Available from: http://hdl.handle.net/11143/17022.

Council of Science Editors:

Sikpa D. L’inflammation : son rôle dans la formation des métastases cérébrales, et les complications liées à la radiothérapie dans leur prise en charge: Inflammation, its role in brain metastases formation, and radio-induced complications in their management. [Doctoral Dissertation]. Université de Sherbrooke; 2020. Available from: http://hdl.handle.net/11143/17022

Open Access Theses and Dissertations