SIRT1 inhibits angiotensin II-induced vascular smooth muscle cell hypertrophy.
Angiotensin II (Ang II) stimulates vascular smooth muscle cell (VSMC) hypertrophy as a critical event in the development of vascular diseases such as atherosclerosis. Sirtuin (SIRT) 1, a nicotinamide adenine dinucleotide dependent deacetylase, has been demonstrated to exert protective effects in atherosclerosis by promoting endothelium-dependent vascular relaxation and reducing macrophage foam cell formation, but its role in VSMC hypertrophy remains unknown. In this study, we tried to investigate the effect of SIRT1 on Ang II-induced VSMC hypertrophy. Results showed that adenoviral-mediated over-expression of SIRT1 significantly inhibited Ang II-induced VSMC hypertrophy, while knockdown of SIRT1 by RNAi resulted in an increased [(3)H]-leucine incorporation of VSMC. Accordingly, nicotinamide adenine dinucleotide phosphate oxidase 1 (Nox1) expression induced by Ang II was inhibited by SIRT1 in VSMCs. SIRT1 activator resveratrol decreased, whereas endogenous SIRT1 inhibitor nicotinamide increased Nox1 expression in A7r5 VSMCs. Furthermore, transcription factor GATA-6 was involved in the down-regulation of Nox1 expression by SIRT1. These results provide new insight into SIRT1's anti-atherogenic properties by suppressing Ang II-induced VSMC hypertrophy.
National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Li
L
Li
Peng
P
Gao
Huina
H
Zhang
Houzao
H
Chen
Wei
W
Zheng
Xiang
X
Lv
Tingting
T
Xu
Yusheng
Y
Wei
Depei
D
Liu
Chihchuan
C
Liang
D000804:Angiotensin II; D000818:Animals; D002460:Cell Line; D050993:GATA6 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006984:Hypertrophy / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology*; D009247:NADH, NADPH Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D000074624:NADPH Oxidase 1; D051381:Rats; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism*
D050993:GATA6 Transcription Factor; D000804:Angiotensin II; D009247:NADH, NADPH Oxidoreductases; D000074624:NADPH Oxidase 1; C000614711:NOX1 protein, mouse; C000614712:NOX1 protein, rat; C488368:Sirt1 protein, rat; D056564:Sirtuin 1