Guanxin V alleviates acute myocardial infarction by restraining oxidative stress damage, apoptosis, and fibrosis through the TGF-β1 signalling pathway

Abstract

BackgroundOxidative stress, apoptosis, and fibrosis have important roles in acute myocardial infarction, which is the main cause of global morbidity and mortality. Guanxin V significantly ameliorates acute myocardial infarction, the underlying mechanism, however, is still unclear. PurposeIn this study, we detected the anti-oxidative, anti-apoptotic, and anti-fibrosis effects of Guanxin V on acute myocardial infarction. MethodsWe used left anterior descending coronary artery ligation to construct an acute myocardial infarction model. Cardiac function, heart weight, infarction size, and histopathology were measured. Cardiomyocytes were treated with hydrogen peroxide to build an in vitro model. Cell apoptosis, fibrosis, and reactive oxygen species-related markers were tested. We observed the mitochondrial ultrastructure through transmission electron microscopy. The levels of collagens and TGF-β1 signalling were measured. The lentiviral vector containing the full-length TGF-β1 sequence was administered to investigate the rescue role of Guanxin V. ResultsGuanxin V significantly decreased apoptosis and inhibited oxidative stress damage and fibrosis in acute myocardial infarction. Hydrogen peroxide could stimulate cardiomyocytes to produce reactive oxygen species and Guanxin V could significantly reverse hydrogen peroxide-induced cell damage, inhibit oxidative stress damage, apoptosis, and fibrosis, and enhance mitochondrial dynamic balance. Mechanistically, Guanxin V attenuated oxidative stress damage, apoptosis, and fibrosis induced by the TGF-β1 signalling pathway activation. ConclusionsGuanxin V effectively relieved apoptosis, oxidative stress damage, and fibrosis through down-regulating the TGF-β1 signalling pathway, which enhances the knowledge of the cellular and molecular mechanism of Guanxin V in treating acute myocardial infarction.