(Circulation. 2001;103:736.)
© 2001 American Heart Association, Inc.
Basic Science Reports |
Effects of Early Angiotensin-Converting Enzyme Inhibition on Cardiac Gene Expression After Acute Myocardial Infarction
From the Cardiovascular Research Department, Genentech, Inc, South San Francisco, and Affymetrix, Inc, Santa Clara (T.A.A., B.S., G.d.F.), Calif.
Correspondence to Nicholas F. Paoni, PhD, Department of Cardiovascular Research, Genentech, Inc, 1 DNA Way, South San Francisco, CA 94080. E-mail nfp{at}gene.com
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.
Methods and
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.
Key Words: heart failure • molecular biology • cardiomyopathy • genes
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