- 作者：Myung-A. Kim ; Dongheon Yang ; Keisuke Kida ; Natalia Molotkova ; Seon Ju Yeo ; Nissi Varki ; Michikado Iwata ; Nancy D. Dalton ; Kirk L. Peterson ; Wolf-Eberhard Siems ; Thomas Walther ; R ; y T. Cowling ; John Kj
- 关键词：Angiotensin-converting enzyme 2 (ACE2) ; C16 ; renin-angiotensin system ; c-kit+ stem cells ; cardiac remodeling
- 刊名：Journal of Cardiac Failure
- 出版年：2010
- 出版时间：September 2010
- 年：2010
- 卷：16
- 期：9
- 页码：777-785
- 全文大小：208 K
BackgroundThere is evidence that angiotensin-converting enzyme 2 (ACE2) is cardioprotective. To assess this in the post-myocardial infarction (MI) heart, we treated adult male Sprague-Dawley rats with either placebo (PL) or C16, a selective ACE2 inhibitor, after permanent coronary artery ligation or sham operation.Methods and Results
Coronary artery ligation resulting in MI between 25 % to 50 % of the left ventricular (LV) circumference caused substantial cardiac remodeling. Daily C16 administration from postoperative days 2 to 28 at a dose that inhibited myocardial ACE2 activity was associated with a significant increase in MI size and reduction in LV % fractional shortening. Treatment with C16 did not significantly affect post-MI increases in LV end-diastolic dimension but did inhibit increases in wall thickness and fibrosis in non-infarcted LV. On postoperative day 7, C16 had no significant effect on the increased level of apoptosis in the infarct and border zones nor did it significantly affect capillary density surrounding the MI. It did, however, significantly reduce the number of c-kit+ cells in the border region.
Conclusions
These findings support the notion that ACE2 exerts cardioprotective effects by preserving jeopardized cardiomyocytes in the border zone. The reduction in hypertrophy and fibrosis with C16, however, suggests that ACE2 activity has diverse effects on post-MI remodeling.