The Dual Effect and Mechanism of (-)-epicatechin on Hypoxic-induced Proliferation and Apoptosis of Cardiac Fibroblasts

Objective: Cardiovascular diseases impose a considerable economic burden on health services and remain a threat to human being. (-)-Epicatechin [(-)-EPI], a traditional Chinese medicine is applied to treatment against the cardiovascular diseases. Herein, we aimed at investigating the underlying mechanism whereby (-)-EPI affects myocardial fibrosis (MF). Methods: The efficacy of (-)-EPI was determined in mouse models of acute myocardial infarction (AMI) and hypoxia-treated fibroblasts. Western blot and RT-qPCR analyses were conducted to determine TGF-β1, SMAD2 and SMAD3 expression, as collagen content was detected. CCK-8 assay and flow cytometry were carried out to detect fibroblast proliferation and apoptosis. HE and Masson staining reflected the histological change of myocardial tissues Results: Compared to sham-operated mice, AMI group exhibited MF and hypoxia-treated cardiac fibroblasts proliferation was restrained and apoptosis was increased. Treatment with (-)-EPI significantly attenuated the MF condition and restored fibroblast proliferation and apoptosis, whereas these effects were abrogated by the TGF-β1 agonist HY-100347A. (-)-EPI administration caused a decline in TGF-β1, SMAD2 and SMAD3 expression. Mechanistically, (-)-EPI targeting TGF-β signaling inhibits collagen deposition and attenuates MF. Conclusion: Collectively, (-)-EPI could improve MF following AMI through down-regulation of TGF-β1 signaling, providing a novel insight into treatment against the cardiovascular diseases.