ACE2 overexpression ameliorates left ventricular remodeling and dysfunction in a rat model of myocardial infarction.
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.
Zhao
Yu Xia
YX
The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University Qilu Hospital, Jinan, Shandong, 250012, China.
Yin
Hui Qiu
HQ
Yu
Qing Tao
QT
Qiao
Yun
Y
Dai
Hong Yan
HY
Zhang
Ming Xiang
MX
Zhang
Lei
L
Liu
Yun Fang
YF
Wang
Lai Cheng
LC
Liu
De Shan
DS
Deng
Bi Ping
BP
Zhang
Yue Hui
YH
Pan
Chun Ming
CM
Song
Huai Dong
HD
Qu
Xun
X
Jiang
Hong
H
Liu
Chun Xi
CX
Lu
Xiao Ting
XT
Liu
Bin
B
Gao
Fei
F
Dong
Bo
B
D000804:Angiotensin II / Q000378:metabolism; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D004195:Disease Models, Animal; D005355:Fibrosis / Q000378:metabolism; D015870:Gene Expression; D008297:Male; D009203:Myocardial Infarction / Q000503:physiopathology*; D009206:Myocardium / Q000201:enzymology / Q000473:pathology*; D007703:Peptidyl-Dipeptidase A / Q000235:genetics* / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D011921:Rats, Inbred WKY; D020257:Ventricular Remodeling
D000804:Angiotensin II; D007703:Peptidyl-Dipeptidase A; C000705329:Ace2 protein, rat; D000085962:Angiotensin-Converting Enzyme 2