Heart ischemia is an irreversible condition that occurs via decreased blood flow in vessels by genetic factors, molecular regulators, and environmental conditions. The microRNAs binding to 3´UTR of target genes can influence gene expression and play pivotal roles in several mechanisms identified as a potential biomarker to the pathogenesis. We have screened a pool of microRNAs and mRNAs according to their potential correlation to myocardial ischemia based on artificial intelligence. We constructed the hub genes and mRNA-microRNA networks by R programing language and in silico analysis. Moreover, we calculated the binding affinity of the 3D structure of proanthocyanidin on VEGFα and GATA4 to ameliorate heart tissue after ischemia. Then we treated rats with 300 mg/kg proanthocyanidins and exercised in different intensity and duration times (low, moderate, and high-intensity interval training) for 14 weeks. In the second step, after 14 weeks, isoproterenol hydrochloride was injected into the rats, and myocardial ischemia was induced. We indicated that VEGFα, GATA4, and GJA1 axis associated with miR-27a-3p, miR-499-5p, miR-206-3p, miR-208a-3p are regulatable after 14 weeks of exercise training and proanthocyanidin extract consumption and could prevent myocardial injuries in ischemia. Moreover, we revealed different intensity and duration times, and proanthocyanidin modulated the microRNA-mRNA interaction in rats with myocardial ischemia. Proanthocyanidin consumption as a bioactive compound may significantly ameliorate myocardial dysfunction and offset pathological hallmarks of myocardial ischemia. Moreover, exercise has protective effects on myocardial tissue by reprograming genes and genetic regulator factors. PRACTICAL APPLICATIONS: Complimentary medicine identified Proanthocyanidin and exercise are recognized as effective methods to prevent and improve Myocardial ischemia. According to medical biology servers, we explored the VEGFα, GATA4, and GJA1 axis associated with miR-27a-3p, miR-499-5p, miR-206-3p, miR-208a-3p as a vital pathomechanism of myocardial ischemia. Furthermore, proanthocyanidin extract is the effective compound that could has protective effects on myocardial tissue by reprograming genes and genetic regulator factors. Furthermore, proanthocyanidin and swimming training might recover myocardial dysfunction and regulate the hub genes and mRNA-microRNA networks.
Keywords: VEGFα; exercise training; heart ischemia; microRNAs; myocardial ischemia; proanthocyanidin.
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