| Aldosterone may contribute to heart failure and myocardial infarction (MI). Post-infarction and heart failure trial (EPHESUS) demonstrated a dramatic reduction in mortality and hospitalization for patients randomized to eplerenone (selective aldosterone antagonist). We explored the mechanism of aldosterone post-MI in a rat model. Sprague Dawley rats (N = 100) underwent LAD ligation or sham and then randomized to sham with vehicle, MI with Vehicle, and MI with eplerenone in rat chow. At day 35 post-MI, animals on eplerenone treatment had improved heart morphology and ventricular function evidenced by improved LV systolic pressure, contractility, relaxation, and compliance. Eplerenone treatment decreased collagen fraction in the contralateral viable zone, as mirrored by MMP2/TIMP2 ratios. Microarray analysis in the infarct region revealed down-regulation of MMP12 and MMP14, and up-regulation of Collagen type II alpha 1, confirmed by traditional molecular techniques. We propose a novel mechanism whereby aldosterone contributes to adverse infarct remodeling and heart failure through matrix modulation and collagen alterations. Aldosterone antagonists may have important therapeutic potential following myocardial infarction. |
