Overexpression of ACE2 enhances plaque stability in a rabbit model of atherosclerosis

被引：183

作者：

Dong, Bo ^{[2
,3
]}

Zhang, Cheng ^{[2
]}

Feng, Jing Bo ^{[2
]}

Zhao, Yu Xia ^{[2
]}

Li, Shu Ying ^{[2
]}

Yang, Ya Pei ^{[2
]}

Dong, Qiu Li ^{[2
]}

Deng, Bi Ping ^{[2
]}

Zhu, Li ^{[2
]}

Yu, Qing Tao ^{[2
]}

Liu, Chun Xi ^{[2
]}

Liu, Bin ^{[2
]}

Pan, Chun Ming ^{[4
]}

Song, Huai Dong ^{[4
]}

Zhang, Ming Xiang ^{[2
]}

Zhang, Yun ^{[1
,2
]}

机构：

[1] Shandong Univ, Qilu Hosp, Chinese Minist Hlth, Jinan 250012, Shandong, Peoples R China

[2] Chinese Minist Educ, Key Lab Cardiovasc Remodeling & Funct Res, Jinan, Shandong, Peoples R China

[3] Shandong Univ, Shandong Prov Hosp, Dept Cardiol, Jinan 250012, Shandong, Peoples R China

[4] Shanghai Jiao Tong Univ, Ctr Mol Med, Shanghai Inst Endocrinol, State Key Lab Med Gen,Ruijin Hosp, Shanghai 200030, Peoples R China

来源：

ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY | 2008年 / 28卷 / 07期

关键词：

atherosclerosis; angiotensin converting enzyme 2; angiotensin; inflammation; plaque stability;

D O I：

10.1161/ATVBAHA.108.164715

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：

Objective-The purpose of this study was to test the hypothesis that ACE2 overexpression may enhance atherosclerotic plaque stability by antagonizing ACE activity and converting angiotensin II to angiotensin 1-7. Methods and Results-Atherosclerotic plaques were induced in the abdominal aorta of 114 rabbits by endothelial injury and atherogenic diet. Gene therapy was performed in group A at week 4 and in group B at week 12, respectively. Each group of rabbits were randomly divided into 3 subgroups which received, respectively, a recombinant ACE2 expressing vector (AdACE2), a control vector AdEGFP and AdACE2+A779, an antagonist of angiotensin 1-7 receptor. Local ACE2 overexpression attenuated the progression of lesions from week 4 to week 8, but not progression of plaque size from week 12 to week 16. In group B rabbits, local ACE2 overexpression resulted in stable plaque compositions, ie, fewer macrophages, less lipid deposition and more collagen contents, higher plaque stability scores, decreased angiotensin II levels, and increased angiotensin 1-7 levels in plaque tissues in the AdACE2 subgroup compared with those in the AdEGFP subgroup. Conclusions-Overexpression of ACE2 results in stabilized atherosclerotic plaques and the mechanism is probably the conversion of vasoconstrictive angiotensin II to vessel protective angiotensin 1-7.

引用

页码：1270 / 1276

页数：7

共 23 条

[1]

Lipid lowering by diet reduces matrix metalloproteinase activity and increases collagen content of rabbit atheroma - A potential mechanism of lesion stabilization [J].