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You searched for +publisher:"Temple University" +contributor:("Song, Wenchao;"). Showing records 1 – 2 of 2 total matches.

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Temple University

1. Pansuria, Meghanaben. EFFECT AND MECHANISM OF HYPERHOMOCYSTEINEMIA ON ENDOTHELIAL INSULIN SIGNALING.

Degree: PhD, 2013, Temple University

Pharmacology

Hyperhomocysteinemia (HHcy) is an independent risk factor for cardiovascular disease (CVD). Both HHcy and insulin resistance (IR) are associated with atherosclerotic CVD. Recent studies have confirmed that insulin is not only a principle regulator of glucose homeostasis but also an important vasoactive hormone involved in the modulation of vascular tone. Epidemiological studies and animal studies have demonstrated the positive correlation of HHcy with IR and diabetes. Nevertheless, the effect and mechanism of HHcy on endothelial insulin signaling and insulin resistance has not been studied. In this study, we investigated the role and mechanism of HHcy on endothelial IR in vivo using transgenic mouse model of HHcy (Tg-hCBS Cbs -/- mice, plasma Hcy levels of 102.6 ┬▒ 9.1┬Ámol/L) and in vitro using human aortic endothelial cells (HAEC). Using bioinformatics approach, we found tissue differential expression of Insulin/PI3K pathway genes in human and mouse. Furthermore, we measured tissue Hcy, S-adenosyl methionine (SAM), S-adenosyl homocysteine (SAH) levels in Tg-hCBS Cbs +/+ mice and examined correlation of insulin signaling genes with tissue Hcy, SAH levels and SAM/SAH ratio. We found negative correlation of Insulin/PI3K signaling genes with Hcy and SAH levels and positive correlation of Insulin/PI3K signaling genes with SAM/SAH ratio. These results led us to hypothesize that HHcy might negatively regulate insulin signaling and further contributes to IR. We found that HHcy impaired glucose metabolism (p<0.01 vs controls [CT]) and insulin sensitivity (p<0.05 vs CT) in Tg-hCBS Cbs -/- mice compared to their littermate controls (Tg-hCBS Cbs -/+ or +/+ mice). Furthermore, HHcy impaired insulin-induced vasorelaxation (31% vs CT, p<0.05) and endothelium-dependent relaxation (26% vs CT, p<0.05) in Tg-hCBS Cbs -/- mouse mesenteric arterioles. HHcy did not affect endothelium-independent relaxation and potassium chloride (KCl) & phenylephrine (PE)-induced contraction responses. Moreover, we found that HHcy significantly inhibited insulin-stimulated Akt and eNOS phosphorylation and activation in HAEC, mesenteric arterial tree, and in aorta. Pre-treatment of mesenteric arterioles with Wortmanin (PI3K inhibitor) and L-NAME (Nitric oxide synthase inhibitor) significantly inhibited insulin-induced vasorelaxation in controls (p<0.05 vs vehicle pre-treatment) but not in Tg-hCBS Cbs -/- mice, suggesting that HHcy impairs insulin-induced PI3K/Akt/eNOS signaling pathway. Moreover, we found that HHcy augmented insulin-induced MAPK pathway in HAEC, mesenteric arteries, and in aorta. In addition, pre-treatment of mesenteric arterioles with MEK inhibitor (PD98059) and endothelin-1A receptor blocker (BQ123) significantly improved (p<0.05 vs vehicle pre-treatment) insulin-induced vasorelaxation in Tg-hCBS Cbs -/- mice. Further analysis of upstream insulin signaling genes show that HHcy downregulated insulin receptor substrates (IRS) 1/2 mRNAs and protein expression but did not affect insulin receptor mRNA…

Advisors/Committee Members: Wang, Hong;, Yang, Xiao-Feng, Ashby, Barrie, Scalia, Rosario, Liu, Ming-Lin, Song, Wenchao;.

Subjects/Keywords: Pharmacology

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APA (6th Edition):

Pansuria, M. (2013). EFFECT AND MECHANISM OF HYPERHOMOCYSTEINEMIA ON ENDOTHELIAL INSULIN SIGNALING. (Doctoral Dissertation). Temple University. Retrieved from http://digital.library.temple.edu/u?/p245801coll10,228447

Chicago Manual of Style (16th Edition):

Pansuria, Meghanaben. “EFFECT AND MECHANISM OF HYPERHOMOCYSTEINEMIA ON ENDOTHELIAL INSULIN SIGNALING.” 2013. Doctoral Dissertation, Temple University. Accessed April 17, 2021. http://digital.library.temple.edu/u?/p245801coll10,228447.

MLA Handbook (7th Edition):

Pansuria, Meghanaben. “EFFECT AND MECHANISM OF HYPERHOMOCYSTEINEMIA ON ENDOTHELIAL INSULIN SIGNALING.” 2013. Web. 17 Apr 2021.

Vancouver:

Pansuria M. EFFECT AND MECHANISM OF HYPERHOMOCYSTEINEMIA ON ENDOTHELIAL INSULIN SIGNALING. [Internet] [Doctoral dissertation]. Temple University; 2013. [cited 2021 Apr 17]. Available from: http://digital.library.temple.edu/u?/p245801coll10,228447.

Council of Science Editors:

Pansuria M. EFFECT AND MECHANISM OF HYPERHOMOCYSTEINEMIA ON ENDOTHELIAL INSULIN SIGNALING. [Doctoral Dissertation]. Temple University; 2013. Available from: http://digital.library.temple.edu/u?/p245801coll10,228447


Temple University

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

Degree: PhD, 2013, Temple University

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 DetailsSimilar RecordsGoogle PlusoneFacebookTwitterCiteULikeMendeleyreddit

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

APA (6th 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 (16th Edition):

Yin, Ying. “CASPASE-1 ACTIVATION IS CRITICAL FOR ENDOTHELIAL CELL ACTIVATION, MONOCYTE MIGRATION, AND EARLY ATHEROGENESIS.” 2013. Doctoral Dissertation, Temple University. Accessed April 17, 2021. http://digital.library.temple.edu/u?/p245801coll10,252725.

MLA Handbook (7th Edition):

Yin, Ying. “CASPASE-1 ACTIVATION IS CRITICAL FOR ENDOTHELIAL CELL ACTIVATION, MONOCYTE MIGRATION, AND EARLY ATHEROGENESIS.” 2013. Web. 17 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 17]. 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

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