Effects of early angiotensin-converting enzyme inhibition on cardiac gene expression after acute myocardial infarction.
BACKGROUND
ACE inhibition after myocardial infarction (MI) has been shown to have beneficial effects on cardiac anatomy and function. The purpose of this study was to examine the effects of ACE inhibition on cardiac gene expression after MI.


RESULTS
Rats were randomized to receive captopril or no treatment 1 day after MI. Eight weeks later, cardiac function and hemodynamics were measured by use of indwelling catheters and perivascular flow probes. Myocardial gene expression was assessed with DNA microarrays and real-time reverse transcription-polymerase chain reaction. The ratios of heart and left ventricular weights to body weight were significantly increased by MI and normalized by captopril. Cardiac index and stroke volume index were lower in the untreated MI group than in sham controls but were normal in the MI+captopril group. Thirty-seven genes were found to be differentially expressed between the untreated MI group and sham controls; 31 were induced and 6 repressed. Captopril partially or completely inhibited changes in 10 of the genes. The 37 genes clustered into 11 functional groups, and 6 had >/=1 genes whose expression was modified by ACE inhibition.


CONCLUSIONS
ACE inhibition after MI inhibits cardiac hypertrophy, preserves cardiac function, and attenuates changes in myocardial gene expression. Gene expression profiling reveals, however, that some elements of the pathophysiology may be unaffected by the treatment and be targets for new therapies.
Jin
H
H
Cardiovascular Research Department, Genentech, Inc, South San Francisco, CA 94080, USA.
Yang
R
R
Awad
T A
TA
Wang
F
F
Li
W
W
Williams
S P
SP
Ogasawara
A
A
Shimada
B
B
Williams
P M
PM
de Feo
G
G
Paoni
N F
NF
D000208:Acute Disease; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight; D002216:Captopril / Q000494:pharmacology*; D004195:Disease Models, Animal; D015870:Gene Expression / Q000187:drug effects*; D006321:Heart / Q000187:drug effects / Q000502:physiology; D006334:Heart Function Tests; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009203:Myocardial Infarction / Q000201:enzymology / Q000235:genetics*; D009929:Organ Size / Q000187:drug effects; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000806:Angiotensin-Converting Enzyme Inhibitors; D002216:Captopril; D007703:Peptidyl-Dipeptidase A