SIRT1 Acts as a Modulator of Neointima Formation Following Vascular Injury in Mice

Rationale:Vascular smooth muscle cell (VSMC) proliferation and migration are crucial events involved in the pathophysiology of vascular diseases. Sirtuin 1 (SIRT1), a class III histone deacetylase (HDAC), has been reported to have the function of antiatherosclerosis, but its role in neointima formation remains unknown. Objective:The present study was designed to investigate the role of SIRT1 in the regulation of neointima formation and to elucidate the underlying mechanisms. Methods and Results:A decrease in SIRT1 expression was observed following carotid artery ligation. smooth muscle cell (SMC)–specific human SIRT1 transgenic (Tg) mice were generated. SIRT1 overexpression substantially inhibited neointima formation after carotid artery ligation or carotid artery wire injury. In the intima of injured carotid arteries, VSMC proliferation (proliferating cell nuclear antigen (PCNA)–positive cells) was significantly reduced. SIRT1 overexpression markedly inhibited VSMC proliferation and migration and induced...