Oligomeric proanthocyanidins protect myocardium by mitigating left ventricular remodeling in isoproterenol-induced...

Extracellular matrix (ECM) remodeling is a major pathophysiological process during post-myocardial infarction (MI). The activation, differentiation, and proliferation of cardiac fibroblasts to myofibroblasts regulate the expression of ECM proteins. The signaling by bone morphogenetic protein (BMP-4), an extracellular ligand of the TGF-β family, has recently been identified as an essential pathway in regulating cardiovascular dysfunctions including myocardial fibrosis. Oligomeric proanthocyanidins (OPC) are well known for their cardioprotective activity. The primary aim of the study was to investigate BMP-4-mediated ECM turnover in cardiac fibrosis during isoproterenol-induced post-MI and its downregulation by OPC. Myocardial injury was evaluated by assaying serum markers LDH and CK. Oxidative stress and the enzymatic and nonenzymatic antioxidant levels were assessed to support the cardioprotective nature of OPC. The total collagen level was analyzed by measuring hydroxyproline levels. The ISO-induced group showed a significant decrease in the levels of antioxidants due to severe oxidative stress and increased expression of BMP-4 which reflects the increased expression of MMP 2 and 9 with a concomitant increase and deposition of fibrillary collagens type I and III responsible for the fibrotic scar formation as evidenced in the histological analysis.BMP-4 activation, thus, is strongly associated with cardiac fibrosis which was downregulated upon OPC supplementation. This study provides an evidence supporting the antifibrotic effect of OPC via regulation of BMP-4-mediated ECM turnover and also substantiates the remarkable antioxidant efficacy of OPC against isoproterenol induced severe oxidative stress and subsequent post-MI cardiac fibrosis.