(-)-Epicatechin Attenuates Myocardial Fibrosis and Apoptosis by Suppressing the Transforming Growth Factor-β1 Pathway in Acute Myocardial Infarction

Abstract

Background: Cardiovascular disease (CAD) are the leading cause of human death, resulting in high morbidity, disability, and mortality. (-)-Epicatechin [(-)-EPI], a traditional Chinese medicine, has been used for treating CAD. This study aims to investigate the role of (-)-EPI in myocardial fibrosis (MF). Methods: We established an acute myocardial infarction (AMI) model mouse. The mice were fed with (-)-EPI and/or SRI-011381 hydrochloride (TGF-β1 agonist, HY-100347A) for 10 days. Hematoxylin and eosin (H&E) staining, Masson staining, and Western blot were used to confirm the effects of (-)-EPI alone or in combination with HY-100347A on the pathological injury, MF, and transforming growth factor-β (TGF-β) pathway in AMI model mice. In vitro experiments were conducted to verify whether (-)-EPI could affect the proliferation, apoptosis, and collagen deposition through the TGF-β1 pathway in myocardial fibroblasts under hypoxia. Results: In the AMI model mice, (-)-EPI was found to attenuate pathological injury and MF, and suppress the TGF-β pathway. However, these inhibitory effects mediated by (-)-EPI could be reversed by the administration of the TGF-β1 pathway activator (HY-100347A). Moreover, myocardial fibroblasts were successfully extracted and certified. (-)-EPI inhibited apoptosis and collagen deposition in hypoxic myocardial fibroblasts by suppressing the TGF-β1 pathway (p < 0.05, p < 0.01, p < 0.001). Conclusions: Collectively, (-)-EPI has the potential to improve pathological injury and MF in AMI patients by suppressing the TGF-β1 pathway. This discovery provides new insights into the treatment of AMI.