Overexpression of Mitofusin 2 inhibited oxidized low-density lipoprotein induced vascular smooth muscle cell proliferation and reduced atherosclerotic lesion formation in rabbit

被引:82
作者
Guo, Yan-hong
Chen, Kuanghueih
Gao, Wei
Li, Qian
Chen, Li
Wang, Gui-song
Tang, Jian
机构
[1] Peking Univ Third Hosp, Dept Cardiol, Key Lab Mol Cardiovasc Sci, Minist Educ, Beijing 100083, Peoples R China
[2] Peking Univ, Inst Cardiovasc Sci, Beijing 100083, Peoples R China
基金
中国国家自然科学基金; 高等学校博士学科点专项科研基金;
关键词
atherosclerosis; Mitofusin; 2; oxidized low-density lipoprotein; proliferation;
D O I
10.1016/j.bbrc.2007.08.191
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Our previous studies have implies that Mitofusin 2 (Mfn2), which was progressively reduced in arteries from ApoE(-/-) mice during the development of atherosclerosis, may take part in pathogenesis of atherosclerosis. In this study, we found that overexpression of Mfn2 inhibited oxidized low-density lipoprotein or serum induced vascular smooth muscle cell proliferation by down-regulation of Akt and ERK phosphorylation. Then we investigated the in vivo role of Mfn2 on the development of atherosclerosis in rabbits using adenovirus expressing Mitofusin 2 gene (AdMfn2). By morphometric analysis we found overexpression of Mfn2 inhibited atherosclerotic lesion formation and intima/media ratio by 66.7% and 74.6%, respectively, compared with control group. These results suggest that local Mfn2 treatment suppresses the development of atherosclerosis in vivo in part by attenuating the smooth muscle cell proliferation induced by lipid deposition and vascular injury. (C) 2007 Elsevier Inc. All rights reserved.
引用
收藏
页码:411 / 417
页数:7
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