Abstract 16336: Age-Associated Reduction of Sirt1 in Vascular Smooth Muscle Accelerates Angiotensin II-Induced Vascular Aging and Abdominal Aortic Aneurysm in Mice
Uncontrolled growth of abdominal aortic aneurysms (AAAs) is a life-threatening vascular disease without effective pharmaceutical therapy. AAA incidence dramatically increases with advancing age in men. However, the molecular mechanism by which aging predisposes to AAAs remains enigmatic. Here, we report that age-associated reduction of Sirt1 in vascular smooth muscle cells (VSMCs) of suprarenal aortas accentuates angiotensin (Ang) II-triggered AAAs. The expression of Sirt1 in samples from patients with AAAs was significantly lower than that in control adjacent aortic sections without aneurysm. Sirt1 expression and Sirt1 activity were significantly lower in aged mice and rats compared with young counterparts. With increased detection of the markers of vascular aging, AngII-induced formation and rupture of AAAs-accelerated in Sirt1-VSMC-specific knockout (SV-KO) mice, but these effects of AngII reduced in Sirt1-VSMC-specific transgenic (SV-Tg) mice compared with their genetic controls. Both AngII-triggered AAAs-related pathological changes and vascular aging were significantly elevated in the aortas of SV-KO mice but were alleviated in those from SV-Tg mice. Finally, chronic administration of Sirt1 activator resveratrol-inhibited vascular aging, AAAs, and AAA-associated pathologies in AngII-infused Apoe-/- mice but not in AngII-infused SV-KO mice. We conclude that age-related Sirt1 reduction in VSMCs predisposes aortas to AAAs and effective Sirt1 activation in VSMCs might prevent AAA formation.
- © 2013 by American Heart Association, Inc.