Effects of ACE2 inhibition in the post-myocardial infarction heart.
BACKGROUND
There 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.


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.
Kim
Myung-A
MA
Seoul National University, Seoul, Korea.
Yang
Dongheon
D
Kida
Keisuke
K
Molotkova
Natalia
N
Yeo
Seon Ju
SJ
Varki
Nissi
N
Iwata
Michikado
M
Dalton
Nancy D
ND
Peterson
Kirk L
KL
Siems
Wolf-Eberhard
WE
Walther
Thomas
T
Cowling
Randy T
RT
Kjekshus
John
J
Greenberg
Barry
B
D000085962:Angiotensin-Converting Enzyme 2; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D003331:Coronary Vessels / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000473:pathology; D005355:Fibrosis / Q000503:physiopathology; D006346:Heart Septum / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D017379:Hypertrophy, Left Ventricular / Q000503:physiopathology; D008297:Male; D009203:Myocardial Infarction / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D009206:Myocardium / Q000473:pathology*; D007703:Peptidyl-Dipeptidase A / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System; D013997:Time Factors; D014463:Ultrasonography
D000806:Angiotensin-Converting Enzyme Inhibitors; D007703:Peptidyl-Dipeptidase A; C000705329:Ace2 protein, rat; D000085962:Angiotensin-Converting Enzyme 2
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