Intermedin induces autophagy and attenuates hypoxia-induced injury in cardiomyocytes by regulation of MALAT1/ULK1.

Myocardial infarction is a predominant cause of cardiovascular diseases with high incidence and death rate worldwide. Although growing evidence has suggested that IMD has significant protective influences on the cardiovascular system, the molecular regulatory mechanism of IMD in hypoxia-induced injury caused by myocardial infarction is urgent to be elucidated. In the present study, we found hypoxia led to a noteworthy enhancement in IMD expression and IMD alleviated hypoxia-induced myocardial injury of NRCMs. Furthermore, IMD was proved to inhibit hypoxia-induced injury by regulating MALAT1. Our findings suggested MALAT1 positively regulated the mRNA and protein expression level of ULK1 and hypoxia induced autophagy of NRCMs. MALAT1 stimulated autophagy to block hypoxia-induced cell injury in NRCMs via upregulation of ULK1 expression. Autophagy suppression abolished the protective capability of IMD overexpression against hypoxia-induced myocardial injury in NRCMs. In a word, our study shed light on the central mechanism of IMD in preventing hypoxia-induced injury caused by myocardial infarction. We confirmed IMD induced autophagy and attenuated hypoxia-induced injury in cardiomyocytes via MALAT1/ULK1, which may contribute to designing effective therapeutic approaches of myocardial infarction.