MicroRNA-297 exerts angiogenesis and cardioprotection after myocardial infarction via through targeting FTO-dependent m6A

Abstract

Abstract Background Emerging evidence suggests that microRNA (miRNA) and m6A RNA methylation are involved Pathogenesis of a variety of cardiovascular diseases, including myocardial infarction. However, the potential role of m6A in regulating ischemic cardiac regeneration and angiogenesis remains unclear. In this study, the effects of our microRNA-297 (miR-297) on myocardial infarction and endothelial cell damage. Methods The intermodulation of miR-297/FTO/VEGF axes was verified by RT-qPCR, western blotting, m6A quantitative assay and Di luciferase reporter detection. At the same time, the expression, function and prognosis of miR-297 in myocardial infarction were studied through RT-qPCR, western blotting and rescue experiments. Results In this study, we identified the downregulation of m6A demethylase FTO and miR-297 in cardiac and hypoxia-induced HUVEC cells after myocardial infarction. The expression of miR-297 significantly inhibited proliferation, migration, and angiogenesis, while knocked down miR-297 had the opposite effect. After myocardial infarction in mice, forced expression of miR-297 by adeno-associated virus significantly decreases expression of VEGF and weakens cardiac function, while simultaneous increased expression of FTO can reverse this effect. Thus, a feedback loop containing the miR-297/FTO/VEGF axis is formed. Conclusion miRNA is involved in m6A-mediated cardiac protection. Determining the role of m6A-regulated miRNAs in cardiac protection may provide new therapeutic and preventive targets for ischemic heart disease.