Electronic Thesis and Dissertation Repository


Master of Science




Dr. J. Geoffrey Pickering


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 aortitis, aortic hemorrhage, and aneurysms in response to Ang II. Therefore, we propose that SIRT6 has an anti-inflammatory role in aortic SMCs that is necessary for maintaining vessel wall integrity in the presence of oxidative stress.

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