SIRT1 inhibits angiotensin Ⅱ-induced vascular smooth muscle cell hypertrophy  

作　　者：Li Li Peng Gao Huina Zhang Houzao Chen Wei Zheng Xiang Lv Tingting Xu Yusheng Wei Depei Liu Chihchuan Liang 

机构地区：[1]National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and PekingUnion Medical College, Beijing 100005, China

出　　处：《Acta Biochimica et Biophysica Sinica》2011年第2期103-109,共7页生物化学与生物物理学报（英文版）

摘　　要：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 [^3H]-leucine incorporation of VSMC. Accordingly, nicotinamide adenine dinucleotide phosphate oxidase 1 （Noxl） expression induced by Ang Ⅱ was inhibited by SIRT1 in VSMCs. SIRT1 activator resveratrol decreased, whereas endogenous SIRT1 inhibitor nicotinamide increased Noxl expression in A7r5 VSMCs. Furthermore, transcription factor GATA-6 was involved in the down-regulation of Noxl expression by SIRT1. These results provide new insight into SIRTI＇s anti-atherogenic properties by suppressing Ang Ⅱ-induced VSMC 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 [^3H]-leucine incorporation of VSMC. Accordingly, nicotinamide adenine dinucleotide phosphate oxidase 1 （Noxl） expression induced by Ang Ⅱ was inhibited by SIRT1 in VSMCs. SIRT1 activator resveratrol decreased, whereas endogenous SIRT1 inhibitor nicotinamide increased Noxl expression in A7r5 VSMCs. Furthermore, transcription factor GATA-6 was involved in the down-regulation of Noxl expression by SIRT1. These results provide new insight into SIRTI＇s anti-atherogenic properties by suppressing Ang Ⅱ-induced VSMC hypertrophy.

关 键 词：SIRT1 VSMC hypertrophy Noxl GATA- 6 angiotensin Ⅱ 

分 类 号：Q463[生物学—生理学] Q575.32