Attenuation of protects cardiomyocytes against hypoxic stress through maintenance of glycolysis.

MiRNAs are a class of endogenous, short, single-stranded, non-coding RNAs, which are tightly linked to cardiac disorders such as myocardial ischemia/reperfusion (I/R) injury. is known to be involved in the hypoxia-induced cardiomyocytes apoptosis. However, the molecular mechanisms are unclear. In the present study, we demonstrate that under low glucose supply, rat cardiomyocytes are susceptible to hypoxia. Under short-time hypoxia, cellular glucose uptake and lactate product are induced but under long-time hypoxia, the cellular glucose metabolism is suppressed. Interestingly, an adaptive up-regulation of by long-time hypoxia was observed both and , leading to suppression of glycolysis in cardiomyocytes. We identified lactate dehydrogenase-A (LDHA) as a direct target of , which binds to the 3'-UTR region of mRNA in cardiomyocytes. Moreover, inhibition of attenuated hypoxia-induced cardiomyocytes dysfunction through restoration of glycolysis. The present study illustrates roles of in the hypoxia-induced cardiomyocytes dysfunction and proposes restoration of glycolysis of dysfunctional cardiomyocytes by inhibiting during I/R might be an effectively therapeutic approach against I/R injury.