Endothelium-specific overexpression of class III deacetylase SIRT1 decreases atherosclerosis in apolipoprotein E-deficient mice

被引：363

作者：

Zhang, Qing-jun ^{[1
]}

Wang, Zhao ^{[1
]}

Chen, Hou-Zao ^{[1
]}

Zhou, Shuang ^{[1
]}

Zheng, Wei ^{[1
]}

Liu, Guang ^{[1
]}

Wei, Yu-sheng ^{[1
]}

Cai, Hua ^{[2
]}

Liu, De-pei ^{[1
]}

Liang, Chih-chuan ^{[1
]}

机构：

[1] Peking Union Med Coll, Sch Basic Med, Chinese Acad Med Sci, Inst Basic Med Sci,Natl Lab Med Mol Biol, Beijing 100005, Peoples R China

[2] Univ Calif Los Angeles, Div Mol Med, Dept Anesthesiol & Med, Cardiovasc Res Labs, Los Angeles, CA USA

来源：

CARDIOVASCULAR RESEARCH | 2008年 / 80卷 / 02期

基金：

中国国家自然科学基金;

关键词：

Endothelial cell; SIRT1; Atherosclerosis; eNOS; Apolipoprotein E;

D O I：

10.1093/cvr/cvn224

中图分类号：

R5 [内科学];

学科分类号：

1002 [临床医学]; 100201 [内科学];

摘要：

Aims Hazardous environmental and genetic factors can damage endothelial cells to induce atherosclerotic vascular disease. Recent studies suggest that class III deacetylase SIRT1 may promote cell survival via novel antioxidative mechanisms. The current study tested the hypothesis that SIRT1, specifically overexpressed in the endothelium, is atheroprotective. Methods and results Human umbilical vein endothelial cells (HUVECs) were used to study the effects of oxidized low-density lipoprotein (LDL) on SIRT1 expression. Endothelial cell-specific SIRT1 transgenic (SIRT1-Tg) mice were used to study the effects of SIRT1 on aortic vascular tone. SIRT1-Tg mice were crossed with apolipoprotein E null (apoE(-/-)) mice to obtain SIRT1-Tg/apoE(-/-) mice for the analysis of atherogenesis in the presence of endothelial overexpression of SIRT1. SIRT1 expression in HUVECs was increased by the treatment with oxidative LDL. Adenoviral-mediated overexpression of SIRT1 was protective of apoptosis of HUVECs. Calorie restriction increased, whereas high-fat diet decreased, the SIRT1 expression in mouse aortas. In SIRT1-Tg mice, high fat-induced impairment in endothelium-dependent vasorelaxation was improved compared with that of wild-type littermates. This was accompanied by an upregualtion of aortic endothelial nitric oxide synthase expression in the SIRT1-Tg mice. The SIRT1-Tg/apoE(-/-) mice had less atherosclerotic lesions compared with apoE(-/-) controls, without affecting blood lipids and glucose levels. Conclusion These results suggest that endothelium-specific SIRT1 overexpression likely suppresses atherogenesis via improving endothelial cell survival and function.

引用

页码：191 / 199

页数：9

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