The essential role of acetyltransferase activity of p300 in matrix remodeling in left anterior descending coronary artery ligation-induced myocardial infarcted heart is documented by the observation that a p300 mutant transgenic mice, with 2-amino acid alteration in the acetyltransferase domain, are protected from myocardial infarction-induced left ventricular dilation, reduced systolic blood pressure and ventricular fibrosis. The gene discussed is EP300; the disease is myocardial infarction.