ACE2 Overexpression Ameliorates Left Ventricular Remodeling and Dysfunction in a Rat Model of Myocardial Infarction

被引：62

作者：

Zhao, Yu Xia ^{[1
,2
]}

Yin, Hui Qiu ^{[1
,2
]}

Yu, Qing Tao ^{[1
,2
]}

Qiao, Yun ^{[1
,2
]}

Dai, Hong Yan ^{[1
,2
]}

Zhang, Ming Xiang ^{[1
,2
]}

Zhang, Lei ^{[1
,2
]}

Liu, Yun Fang ^{[1
,2
]}

Wang, Lai Cheng ^{[3
]}

Liu, De Shan ^{[1
,2
]}

Deng, Bi Ping ^{[1
,2
]}

Zhang, Yue Hui ^{[1
,2
]}

Pan, Chun Ming ^{[4
]}

Song, Huai Dong ^{[4
]}

Qu, Xun ^{[1
,2
]}

Jiang, Hong ^{[1
,2
]}

Liu, Chun Xi ^{[1
,2
]}

Lu, Xiao Ting ^{[1
,2
]}

Liu, Bin ^{[1
,2
]}

Gao, Fei ^{[1
,2
]}

Dong, Bo ^{[1
,2
,3
]}

机构：

[1] Shandong Univ, Qilu Hosp, Key Lab Cardiovasc Remodeling & Funct Res, Chinese Minist Educ, Jinan 250012, Shandong, Peoples R China

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

[3] Shandong Univ, Shandong Prov Hosp, Dept Cardiol, Jinan 250021, Shandong, Peoples R China

[4] Shanghai Jiao Tong Univ, Sch Med, State Key Lab Med Genom, Shanghai Inst Endocrinol,Ctr Mol Med,Ruijin Hosp, Shanghai 200015, Peoples R China

来源：

HUMAN GENE THERAPY | 2010年 / 21卷 / 11期

基金：

中国国家自然科学基金;

关键词：

ANGIOTENSIN-CONVERTING ENZYME-2; GROWTH-FACTOR-BETA; CARDIAC FIBROBLASTS; EXTRACELLULAR-MATRIX; SYSTEM; EXPRESSION; FIBROSIS; RECEPTORS;

D O I：

10.1089/hum.2009.160

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

The purpose of this study was to test the hypothesis that overexpression of angiotensin-converting enzyme 2 (ACE2) may favorably affect left ventricular (LV) remodeling and function after myocardial infarction (MI). The left anterior descending coronary artery was ligated to produce anterior MI in 100 Wistar-Kyoto rats that were randomly divided into Ad-ACE2, Ad-ACE2+A779, Ad-EGFP, model, and sham groups. Two weeks later, rats in the Ad-ACE2 and Ad-EGFP groups received direct intramyocardial injection of Ad-ACE2 and Ad-EGFP, respectively. Rats in the Ad-ACE2+A779 group received both intramyocardial injection of Ad-ACE2 and a continuous intravenous infusion of A779 for 15 days. LV volume and systolic function, the extent of myocardial fibrosis, and levels of ACE2, angiotensin II (Ang II), and collagen I protein expression were evaluated. Four weeks after ACE2 gene transfer, the Ad-ACE2 group showed reduced LV volume, extent of myocardial fibrosis, and expression levels of ACE, Ang II, and collagen I in the myocardium, and increased LV ejection fraction and levels of ACE2 activity and expression in comparison with the Ad-EGFP and model groups. These results suggest that ACE2 overexpression attenuated LV fibrosis and improved LV remodeling and systolic function. In conclusion, overexpression of ACE2 favorably affected the pathological process of LV remodeling after MI by inhibiting ACE activity, reducing AngII levels, and up-regulating Ang-(1-7) expression, thus providing a potential therapeutic target in the treatment of heart failure.

引用

页码：1545 / 1554

页数：10

共 28 条

[1] Osteopontin is produced by rat cardiac fibroblasts and mediates A(II)-induced DNA synthesis and collagen gel contraction [J].