Downregulation of microRNA-429 protects cardiomyocytes against hypoxia-induced apoptosis by increasing Notch1 expression

Myocardial ischemia is a commonly encountered symptom, chiefly as a result of coronary artery and heart diseases in middle-aged and elderly individuals, with a sudden occurrence and a high morbidity. In some cases, myocardial ischemia may lead to the injury and subsequent death of cardiomyocytes, and may finally culminate in myocardial infarction (MI). MI is the leading cause of sudden death and is associated with a high mortality rate. In this study, we focused on the role of microRNA-429 (miR-429) in protecting the cardiomyocytes against apoptosis induced by myocardial ischemia. The culture of human cardiomyocytes under hypoxic conditions was employed to mimic myocardial ischemia. miR-429 expression was upregulated following culture under hypoxic conditions. Subsequently, miR-429 was artificially overexpressed and silenced by transfection with miRNA-mimics and miRNA-inhibitor, respectively. The results revealed that the downregulation of miR-429 expression exerts protective effects against hypoxia-induced apoptosis. Moreover, Notch1 was also proven to be involved in these protective effects. The downregulation of miR-429 was accompanied by the activation of Notch1, as indicated by the significant increase in the protein expression of Notch1. The ectopic expression of Notch1 also inhibited the apoptosis induced by culture under hypoxic conditions. In conclusion, and to the best of our knowledge, our results demonstrate for the first time that the downregulation of miR-429 protects cardiomyocytes against hypoxia-induced apoptosis through Notch1; this may provide the experimental basis for an underlying therapeutic target for myocardial ischemia and consequent MI, as well as the basis for an effective preventive treatment against sudden death.