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 t o have beneficial effects on cardiac anatomy and function, The purpose of t his study was to examine the effects of ACE inhibition on cardiac gene expr ession after MI. Methods and Results-Rats were randomized to receive captopril or no treatme nt 1 day after MI. Eight weeks later, cardiac function and hemodynamics wer e measured by use of indwelling catheters and perivascular flow probes. Myo cardial gene expression was assessed with DNA microarrays and real-time rev erse transcription-polymerase chain reaction. The ratios of heart and left ventricular weights to body weight were significantly increased by MI and n ormalized 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+cap topril group. Thirty-seven genes were found to be differentially expressed between the untreated MI group and sham controls; 31 were induced and 6 rep ressed. Captopril partially or completely inhibited changes in 10 of the ge nes. The 37 genes clustered into 11 functional groups, and 6 had 11 genes w hose expression was modified by ACE inhibition. Conclusions-ACE inhibition after MI inhibits cardiac hypertrophy, preserves cardiac function, and attenuates changes in myocardial gene expression. Ge ne expression profiling reveals, however, that some elements of the pathoph ysiology may be unaffected by the treatment and be targets for new therapie s.