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The Role Of Sirtuin 6 In Maintaining Vascular Integrity, Sharon Z. Leung
The Role Of Sirtuin 6 In Maintaining Vascular Integrity, Sharon Z. Leung
Electronic Thesis and Dissertation Repository
Oxidative stress is an underlying cause for vascular pathologies including inflammation, hypertension, and atherosclerosis. Sirtuins (SIRTs) are a family of NAD+ dependent deacetylases with pronounced roles in cellular metabolism and aging. SIRT6 is expressed in vascular smooth muscle cells (SMCs) and may offer protection from oxidative stress-induced damage. To study the role of SIRT6 in SMCs, we created a novel strain of SMC-specific SIRT6-deficient (SIRT6KO) mice with Cre-lox technology. Because no defects were observed in the aortas of SIRT6KO mice, they were then infused with angiotensin II (Ang II) to induce oxidative stress. Compared with vehicle controls, SIRT6KO mice developed …
Regulation Of Lipid Homeostasis, Inflammatory Signalling And Atherosclerosis By The Peroxisome Proliferator-Activated Receptor Delta, Lazar A. Bojic
Regulation Of Lipid Homeostasis, Inflammatory Signalling And Atherosclerosis By The Peroxisome Proliferator-Activated Receptor Delta, Lazar A. Bojic
Electronic Thesis and Dissertation Repository
The peroxisome proliferator-activated receptor (PPAR) δ is a ligand-dependent transcription factor that has been implicated in metabolic and inflammatory regulation. The molecular and physiological mechanisms by which PPARδ activation regulates lipid metabolism, inflammatory signaling and protection from atherosclerosis in states of metabolic disturbance such as insulin resistance and dyslipidemia, were investigated in a series of in vitro and in vivo studies. In vitro experiments demonstrated that PPARδ activation inhibits atherogenic lipoprotein-induced lipid accumulation and the associated proinflammatory responses. The primary mechanisms for these effects were increased fatty acid β-oxidation, decreased lipoprotein lipase (LPL) activity, reduced MAPK signaling and improved insulin …