Modification of Myosin Gene Expression by Imidapril in Failing Heart due to Myocardial Infarction

J. Wang, X. Liu, B. Ren, H. Rupp, N. Takeda and N. S. Dhalla. Modification of Myosin Gene Expression by Imidapril in Failing Heart due to Myocardial Infarction. Journal of Molecular and Cellular Cardiology (2002) 34, 847–857. The beneficial effects of imidapril, an angiotensin converting enzyme (ACE) inhibitor were investigated on changes in myofibrillar ATPase as well as myosin heavy chain (MHC) content and gene expression due to myocardial infarction (MI). Three weeks after occluding the left coronary artery, rats were treated with or without imidapril (1 mg/kg/day), for 4 weeks. The infarcted hearts exhibited depressed rates of left ventricular (LV) pressure development (57±2.4% reduction) and pressure decay (55.5±1.6% reduction). LV myofibrillar Ca2+ ATPase activity, unlike that in the right ventricle (RV), was decreased in the infarcted animals compared with controls (6.8±0.4 vs 10.3±0.6 μmol Pi/mg/hr). MHC α-isoform contents were decreased by 47 and 41% whereas those of MHC β-isoform were increased by 823 and 1200% in the LV and RV due to MI, respectively. MHC α-isoform mRNA levels were decreased by 55 and 35% whereas those for MHC β-isoform were increased by 50 and 30% in the infarcted LV and RV, respectively. Imidapril treatment partially prevented the changes due to MI in LV function (rate of pressure development, 24±2.3% reduction and rate of pressure decay, 14±1.8% reduction), myofibrillar Ca2+ ATPase activity (8.2±0.7 μmol Pi/mg/hr), MHC protein content (α-MHC, 24% reduction and β-MHC, 525% increase) and MHC gene expression (α-MHC, 18% reduction and β-MHC, 15% increase). The results suggest that the beneficial effects of ACE inhibition on the failing heart are associated with improvements in myofibrillar ATPase activities as well as prevention of changes in MHC isozyme protein contents and their gene expression. Copyright 2002 Elsevier Science Ltd. All rights reserved.