+publisher:"Universidade Estadual de Campinas" +contributor:("Werneck, Claudio Chrysostomo, 1966-")

Universidade Estadual de Campinas

1. Braga, Guilherme Gambogi, 1985-. Avaliação dos mecanismos de ação do losartan em cultura de fibroblastos de derme deficientes em fibrilina-1: Evaluation of losartan action mechanism in dermal fibroblasts derived from fibrillin-1 deficient mice.

Degree: 2015, Universidade Estadual de Campinas

URL: http://repositorio.unicamp.br/jspui/handle/REPOSIP/314061

► Abstract: Fibrillin-1 is an important component of the microfibrils network present in elastic fibers. Mutations in fibrillin-1 gene imply in the development of Marfan Syndrome.… (more)

▼ Abstract: Fibrillin-1 is an important component of the microfibrils network present in elastic fibers. Mutations in fibrillin-1 gene imply in the development of Marfan Syndrome. This disease affects elastogenesis in lungs, skin, cardiovascular system and eyes. Recent studies determined that unbalanced TGF-beta activity is an important factor in the symptoms observed this syndrome. These alterations can be reversed by the use of TGF-beta blockers such as the drug losartan. The mechanisms by which the drug losartan act are not described in the literature. Thus, using a model of primary culture cells (dermal fibroblasts) the elastogenic profile by immunofluorescence, zimograph in situ, Real-Time PCR, electronic microscopy and western-blotting of matrix proteins and signal molecules of elastic fiber synthesis and degradation was evaluated. The data presented suggest a joint reduction of the deposition of proteins MAGP-1 (83%), Tropoelastina (87.5%) and Fibilina-1 (86%) in the extracellular matrix; an increase in the activity and also the levels of gene expression of matrix metalloproteinases MMP-2 and MMP-9, activation of the signaling cascade canonical (SMAD-2) and not canonical (ERK1/2 and JNK-1) of TGF-beta and increased levels of reactive oxygen species (ROS) in cultures of fibroblasts in the dermis derived from mice deficient in fibrillin-1. While using the losartan drug (100 ?M/L) to treat these cells it was possible to observe an increase in deposition of MAGP-1 (71.5%) and Tropoelastina (68.5%) in the extracellular matrix, reduction of activity and gene expression of matrix metalloproteinases MMP-2 and MMP-9 and inactivation of canonical signaling (SMAD-2) and not canonical (ERK1/2 and JNK-1) activity of TGF-beta. In general, our data suggest an increase in the degradation of molecules components of elastic fibers in culture of fibroblasts in the dermis derived from mice deficient in fibrillin-1 as a function in the increase in the expression of MMPs 2 and 9. This increase in the degradation of the extracellular matrix may be the result of lower levels of fibrillin-1 in the matrix produced by these cells, super activating the canonical signaling (SMAD-2) and non-canonical (ERK1/2 and JNK-1) of TGF-beta, which reflects the activation of ROS and consequently the activation of proteases The treatment with losartan probably takes the reverse path reducing the super activation of the signaling cascade of TGF-beta as well as the activation of metalloproteinases, indirectly increase in the deposition of MAGP-1 and Tropoelastina in the extracellular matrix of these cells Advisors/Committee Members: UNIVERSIDADE ESTADUAL DE CAMPINAS (CRUESP), Werneck, Claudio Chrysostomo, 1966- (advisor), Universidade Estadual de Campinas. Instituto de Biologia (institution), Programa de Pós-Graduação em Biologia Funcional e Molecular (nameofprogram), Cardoso, Alexandre Bruni (committee member), Felisbino, Sérgio Luis (committee member), Brocchi, Marcelo (committee member), Kobarg, Jörg (committee member).

Subjects/Keywords: Marfan, Sindrome de; Fator de crescimento transformador beta; Losartan; Fibroblastos; Fibrilina-1; Marfan syndrome; Transforming growth factor beta; Losartan; Fibroblasts; Fibrillin-1

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

APA (6^th Edition):

Braga, Guilherme Gambogi, 1. (2015). Avaliação dos mecanismos de ação do losartan em cultura de fibroblastos de derme deficientes em fibrilina-1: Evaluation of losartan action mechanism in dermal fibroblasts derived from fibrillin-1 deficient mice. (Thesis). Universidade Estadual de Campinas. Retrieved from http://repositorio.unicamp.br/jspui/handle/REPOSIP/314061

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):

Braga, Guilherme Gambogi, 1985-. “Avaliação dos mecanismos de ação do losartan em cultura de fibroblastos de derme deficientes em fibrilina-1: Evaluation of losartan action mechanism in dermal fibroblasts derived from fibrillin-1 deficient mice.” 2015. Thesis, Universidade Estadual de Campinas. Accessed January 17, 2021. http://repositorio.unicamp.br/jspui/handle/REPOSIP/314061.

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

MLA Handbook (7^th Edition):

Braga, Guilherme Gambogi, 1985-. “Avaliação dos mecanismos de ação do losartan em cultura de fibroblastos de derme deficientes em fibrilina-1: Evaluation of losartan action mechanism in dermal fibroblasts derived from fibrillin-1 deficient mice.” 2015. Web. 17 Jan 2021.

Vancouver:

Braga, Guilherme Gambogi 1. Avaliação dos mecanismos de ação do losartan em cultura de fibroblastos de derme deficientes em fibrilina-1: Evaluation of losartan action mechanism in dermal fibroblasts derived from fibrillin-1 deficient mice. [Internet] [Thesis]. Universidade Estadual de Campinas; 2015. [cited 2021 Jan 17]. Available from: http://repositorio.unicamp.br/jspui/handle/REPOSIP/314061.

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

Council of Science Editors:

Braga, Guilherme Gambogi 1. Avaliação dos mecanismos de ação do losartan em cultura de fibroblastos de derme deficientes em fibrilina-1: Evaluation of losartan action mechanism in dermal fibroblasts derived from fibrillin-1 deficient mice. [Thesis]. Universidade Estadual de Campinas; 2015. Available from: http://repositorio.unicamp.br/jspui/handle/REPOSIP/314061

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

Universidade Estadual de Campinas

2. Vassequi-Silva, Tallita, 1985-. Avaliação da função da MAGP-1 na trombogênese arterial: Evaluation of MAGP1 function in arterial thrombogenesis.

Degree: 2015, Universidade Estadual de Campinas

URL: http://repositorio.unicamp.br/jspui/handle/REPOSIP/314058

► Abstract: MAGP-1 is a glycoprotein present in the elastic fibers, functioning as part of the microfibrils components. Studies have shown that MAGP-1 expression is critical… (more)

▼ Abstract: MAGP-1 is a glycoprotein present in the elastic fibers, functioning as part of the microfibrils components. Studies have shown that MAGP-1 expression is critical for vascular development and is associated with decreased interaction between integrins and the extracellular matrix in zebra fish. Also MAGP-1 interacts with von Willebrand factor and the active form of TGF-? and BMP. In mice lacking MAGP-1, thrombus formation is delayed, increasing the occlusion time of carotid artery despite normal blood coagulation in vitro. MAGP-containing microfibrils may play a role in hemostasis and thrombosis. In this work, we evaluated the function of MAGP-1 and its relation to TGF-? in the arterial thrombosis process. For this purpose, we obtained and analyzed a mutated MAGP1 (VG1) protein, its participation in the arterial thrombosis formation and its interaction with important proteins in the coagulation process. We analyzed thrombus formation time in wild type and MAGP-1-deficency mice. The potential participation of TGF-? in this process was accessed when we treated both wild type and MAGP-1-/- mice with losartan and captopril. Besides, we evaluated the gelatinolytic activity in the arterial walls. The MAGP-1 mutation avoided its thrombus formation time recovery, although the mutated MGP-1 still interacting with vWF and fibronectin. Losartan and captopril were able to recover the thrombus formation time without changing blood pressure, aPTT and PT, platelet aggregation and adhesion, but increased gelatinases activity. Our results suggest that both treatments are effective in the prevention of the sub-endothelial ECM degradation, allowing the recovery of normal thrombus formation Advisors/Committee Members: UNIVERSIDADE ESTADUAL DE CAMPINAS (CRUESP), Werneck, Claudio Chrysostomo, 1966- (advisor), Universidade Estadual de Campinas. Instituto de Biologia (institution), Programa de Pós-Graduação em Biologia Funcional e Molecular (nameofprogram), Paschoal, Sisi Marcondes (committee member), Oliva, Maria Luiza Vilela (committee member), Gadelha, Fernanda Ramos (committee member), Felisbino, Sérgio Luis (committee member).

Subjects/Keywords: Glicoproteínas associadas a microfibrila-1; Trombose arterial; Fator de crescimento transformador beta; Losartan; Captopril; Microfibril-associated glycoprotein-1; Arterial thrombosis; Transforming growth factor beta; Losartan; Captopril

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

APA (6^th Edition):

Vassequi-Silva, Tallita, 1. (2015). Avaliação da função da MAGP-1 na trombogênese arterial: Evaluation of MAGP1 function in arterial thrombogenesis. (Thesis). Universidade Estadual de Campinas. Retrieved from http://repositorio.unicamp.br/jspui/handle/REPOSIP/314058

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):

Vassequi-Silva, Tallita, 1985-. “Avaliação da função da MAGP-1 na trombogênese arterial: Evaluation of MAGP1 function in arterial thrombogenesis.” 2015. Thesis, Universidade Estadual de Campinas. Accessed January 17, 2021. http://repositorio.unicamp.br/jspui/handle/REPOSIP/314058.

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

MLA Handbook (7^th Edition):

Vassequi-Silva, Tallita, 1985-. “Avaliação da função da MAGP-1 na trombogênese arterial: Evaluation of MAGP1 function in arterial thrombogenesis.” 2015. Web. 17 Jan 2021.

Vancouver:

Vassequi-Silva, Tallita 1. Avaliação da função da MAGP-1 na trombogênese arterial: Evaluation of MAGP1 function in arterial thrombogenesis. [Internet] [Thesis]. Universidade Estadual de Campinas; 2015. [cited 2021 Jan 17]. Available from: http://repositorio.unicamp.br/jspui/handle/REPOSIP/314058.

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

Council of Science Editors:

Vassequi-Silva, Tallita 1. Avaliação da função da MAGP-1 na trombogênese arterial: Evaluation of MAGP1 function in arterial thrombogenesis. [Thesis]. Universidade Estadual de Campinas; 2015. Available from: http://repositorio.unicamp.br/jspui/handle/REPOSIP/314058

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

Universidade Estadual de Campinas

3. Nery-Diez, Ana Cláudia Coelho, 1980-. Avaliação da função da fibrilina-1 na trombogênese arterial: Evaluation of the role of fibrillin-1 in arterial thrombosis.

Degree: 2013, Universidade Estadual de Campinas

URL: http://repositorio.unicamp.br/jspui/handle/REPOSIP/314064

► Abstract: Recent works show that an increased activation of the TGF-? is associated with most of the symptoms of the Marfan syndrome. Studies using mouse… (more)

▼ Abstract: Recent works show that an increased activation of the TGF-? is associated with most of the symptoms of the Marfan syndrome. Studies using mouse models of Marfan treated with losartan have been shown to prevent the degradation of the elastic matrix. Other investigators suggest that the metalloproteinases and the noncanonical ERK signaling are involved in the breakdown of the elastic fiber, which results in the aneurysm. In this study we investigated the role of fibrillin-1 in the arterial thrombosis model using mouse models of Marfan. We analyzed thrombus formation, platelet levels, APTT, PT and TT time, hemodynamic parameter, TGF-? levels, MMP activity as well as platelets, elastic fibers morphology and thrombus. This study demonstrated that Fbn1mg?/+ mice take about 120±21,07 minutes for the thrombus to be formed when compared with wild type, 58±7,16. When these Fbn1mg?/+ mice were treated with antihypertensive losartan and captopril the time taken for the thrombus formation was reduced in 57,5% and 67,5%, respectively. The activity of metalloproteinases and activity TGF-? was increased in the Fbn1mg?/+, however no significant difference between the hemodynamic parameters, levels of totals TGF-?, morphological platelets, elastic fiber and thrombus were observed. Finally, the results suggested that fibrillin-1 interferes with this process and antihypertensive affect the physiology of Fbn1mg?/+ mice. This study suggested that somehow drugs interfere with elastic matrix remodeling due to a decrease in the activity of matrix metalloproteinases which results in the recovery time of thrombus formation Advisors/Committee Members: UNIVERSIDADE ESTADUAL DE CAMPINAS (CRUESP), Werneck, Claudio Chrysostomo, 1966- (advisor), Universidade Estadual de Campinas. Instituto de Biologia (institution), Programa de Pós-Graduação em Biologia Funcional e Molecular (nameofprogram), Pimentel, Edson Rosa (committee member), Brocchi, Marcelo (committee member), Monteiro, Robson de Queiroz (committee member), Oliva, Maria Luiza Vilela (committee member).

Subjects/Keywords: Fibrilina-1; Matriz extracelular; Trombose; Agentes hipotensores; Fator de crescimento transformador beta; Fibrillin-1; Extracellular matrix; Thrombosis; Antihypertensive agents; Transforming growth factor beta1

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

APA (6^th Edition):

Nery-Diez, Ana Cláudia Coelho, 1. (2013). Avaliação da função da fibrilina-1 na trombogênese arterial: Evaluation of the role of fibrillin-1 in arterial thrombosis. (Thesis). Universidade Estadual de Campinas. Retrieved from http://repositorio.unicamp.br/jspui/handle/REPOSIP/314064

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):

Nery-Diez, Ana Cláudia Coelho, 1980-. “Avaliação da função da fibrilina-1 na trombogênese arterial: Evaluation of the role of fibrillin-1 in arterial thrombosis.” 2013. Thesis, Universidade Estadual de Campinas. Accessed January 17, 2021. http://repositorio.unicamp.br/jspui/handle/REPOSIP/314064.

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

MLA Handbook (7^th Edition):

Nery-Diez, Ana Cláudia Coelho, 1980-. “Avaliação da função da fibrilina-1 na trombogênese arterial: Evaluation of the role of fibrillin-1 in arterial thrombosis.” 2013. Web. 17 Jan 2021.

Vancouver:

Nery-Diez, Ana Cláudia Coelho 1. Avaliação da função da fibrilina-1 na trombogênese arterial: Evaluation of the role of fibrillin-1 in arterial thrombosis. [Internet] [Thesis]. Universidade Estadual de Campinas; 2013. [cited 2021 Jan 17]. Available from: http://repositorio.unicamp.br/jspui/handle/REPOSIP/314064.

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

Council of Science Editors:

Nery-Diez, Ana Cláudia Coelho 1. Avaliação da função da fibrilina-1 na trombogênese arterial: Evaluation of the role of fibrillin-1 in arterial thrombosis. [Thesis]. Universidade Estadual de Campinas; 2013. Available from: http://repositorio.unicamp.br/jspui/handle/REPOSIP/314064

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

Universidade Estadual de Campinas

4. Norberto, Douglas Ricardo, 1970-. Aspectos termodinâmicos e bases moleculares na interação de proteínas monoméricas com agentes desnaturantes e alta pressão hidrostática: Thermodynamic aspects and molecular basis of monomeric proteins interaction with desnaturants and high hydrostatic pressure.

Degree: 2011, Universidade Estadual de Campinas

URL: http://repositorio.unicamp.br/jspui/handle/REPOSIP/314013

► Abstract: Urea denatures proteins at different concentrations, depending on the experimental conditions and the protein. We investigated the pressure-induced denaturation of bovine serum albumin (BSA)… (more)

Subjects/Keywords: Proteínas monoméricas; Desnaturação proteica; Alta pressão hidrostática; Termodinâmica; Albumina de soro bovino; Monomeric proteins; Protein desnaturation; High hydrostatic pressure; Thermodynamics; Bovine serum albumin

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

APA (6^th Edition):

Norberto, Douglas Ricardo, 1. (2011). Aspectos termodinâmicos e bases moleculares na interação de proteínas monoméricas com agentes desnaturantes e alta pressão hidrostática: Thermodynamic aspects and molecular basis of monomeric proteins interaction with desnaturants and high hydrostatic pressure. (Thesis). Universidade Estadual de Campinas. Retrieved from http://repositorio.unicamp.br/jspui/handle/REPOSIP/314013

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):

Norberto, Douglas Ricardo, 1970-. “Aspectos termodinâmicos e bases moleculares na interação de proteínas monoméricas com agentes desnaturantes e alta pressão hidrostática: Thermodynamic aspects and molecular basis of monomeric proteins interaction with desnaturants and high hydrostatic pressure.” 2011. Thesis, Universidade Estadual de Campinas. Accessed January 17, 2021. http://repositorio.unicamp.br/jspui/handle/REPOSIP/314013.

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

MLA Handbook (7^th Edition):

Norberto, Douglas Ricardo, 1970-. “Aspectos termodinâmicos e bases moleculares na interação de proteínas monoméricas com agentes desnaturantes e alta pressão hidrostática: Thermodynamic aspects and molecular basis of monomeric proteins interaction with desnaturants and high hydrostatic pressure.” 2011. Web. 17 Jan 2021.

Vancouver:

Norberto, Douglas Ricardo 1. Aspectos termodinâmicos e bases moleculares na interação de proteínas monoméricas com agentes desnaturantes e alta pressão hidrostática: Thermodynamic aspects and molecular basis of monomeric proteins interaction with desnaturants and high hydrostatic pressure. [Internet] [Thesis]. Universidade Estadual de Campinas; 2011. [cited 2021 Jan 17]. Available from: http://repositorio.unicamp.br/jspui/handle/REPOSIP/314013.

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

Council of Science Editors:

Norberto, Douglas Ricardo 1. Aspectos termodinâmicos e bases moleculares na interação de proteínas monoméricas com agentes desnaturantes e alta pressão hidrostática: Thermodynamic aspects and molecular basis of monomeric proteins interaction with desnaturants and high hydrostatic pressure. [Thesis]. Universidade Estadual de Campinas; 2011. Available from: http://repositorio.unicamp.br/jspui/handle/REPOSIP/314013

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

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