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Background: Ischemic heart disease has long been a leading cause of morbidity and mortality worldwide.Timely reperfusion after the onset of ischemia has proven to be the most effective therapy,which can limit myocardial infarct size,reduce cardiomyocyte apoptosis and reverse contractile dysfunction.However,after the restoration of blood flow to the ischemic regions of the myocardium a paradoxical increase in cardiomyocyte death occurs.Thus,the development of novel strategies to preventing myocyte death after the onset of reperfusion is necessary for improving clinical outcomes in patients with ischemic heart disease.Autophagy (or,more precisely,macroautophagy) is a conserved,tightly regulated intracellular catabolic process by which mammalian cells degrade and recycle the damaged and dysfunctional macromolecules and organelles.Enhanced levels of autophagy have been observed in the heart during both ischemia and reperfusion.Studies reported that autophagy has a dual opposite role in the heart depending on the stimulus.Enhancing autophagy can promote survival in response to milder stress,such as brief hypoxia and low levels of oxidative stress,while severe stress,such as prolonged hypoxia or subsequent reperfusion,results in excessive autophagy which may cause cell death by triggering excessive self-digestion of essential proteins and organelles.Manipulation of autophagy may represent a potential future therapeutic target to protect against ischemia/reperfusion (I/R)-induced cardiomyocytes death and preserve cardiac function.MicroRNAs (miRNAs) are endogenous,noncoding,single-stranded RNAs of approximately 22 nucleotides,which can directly regulate more than 30% of the genes in a cell.miRNAs are also involved in several biological processes and are major regulators of cell differentiation,growth,proliferation,and apoptosis.Recently,the roles of miR-21 on cardiovascular biology and disease have received significant attention.miR-21 is aberrantly expressed in many cardiovascular diseases and has been found to play important roles in these cardiovascular disorders by both loss-of-function and gain-of-function approaches.To demonstrate that whether miR-21 could influence autophagy and disclose the potential molecular mechanismsduring I/R in cardiomyocytesmay provide a novel strategy protecting against ischemia/reperfusion.