P10 miRNA-30 family inhibition protects against cardiac ischemic injury by regulating cystathionine-gamma-lyase expression

Background Myocardial infarction (MI) is a leading cause of death globally. MicroRNAs (miRs) have been identified as a novel class of MI injury regulators. Hydrogen sulfide (H 2 S) is a gaseous signaling molecule that regulates cardiovascular function. The purpose of this study was to explore the role of the miR-30 family in protecting against MI injury by regulating H 2 S production. Methods and Results Two days after coronary artery ligations in rats, the expression of miR-30 family was significantly upregulated in the non-infarct and border zone regions. However, the CSE expression was just the opposite. The overexpression of each miR-30 family member decreased mRNA and protein levels of CSE and reduced H 2 S production. In contrast, silencing the whole miR-30 family resulted in elevated CSE expression and increased H 2 S production. Forced expression of the miR-30 family aggravated hypoxia-induced myocardial cell injury. This was reversed by locked nucleic acid (LNA)-miR-30 family inhibitor transfection. Systemic delivery of a LNA-miR-30 family inhibitor correspondingly repressed the miR-30 family in mouse cardiac tissue and increased CSE expression and H 2 S production. The therapeutic targeting of the miR-30 family in mice reduced infarct size, decreased apoptotic cell number in the peri-infarct region, and improved cardiac function in response to MI, whereas miR-30b overexpression by lentivirus in vivo exacerbated MI injury. Conclusion The inhibition of miR-30 family expression in the heart can protect against mouse cardiac ischemic injury by increasing CSE expression and H 2 S production, indicating the therapeutic potential of miR-30 for cardiac diseases associated with MI injury.