MiR‐129‐5p alleviates myocardial injury by targeting suppressor of cytokine signaling 2 after ischemia/reperfusion

Abstract

Abstract Acute myocardial infarction (AMI) remains one of the leading causes of morbidity and mortality worldwide. Ischemia/reperfusion (I/R), the most common consequence of AMI treatment, may induce severe myocardial cell injury, yet the precise mechanism continues to be enigmatic. In the present study, we found that miR‐129‐5p was significantly downregulated in mouse I/R model. Then, we overexpressed miR‐129‐5p via intravenous injection of specific miR‐129‐5p agomir before I/R model establishment. MiR‐129‐5p overexpression dramatically alleviated myocardial injury in I/R mice as evidenced by reduced lactate dehydrogenase (LDH) activity, malondialdehyde (MDA) content, and infract size. We further detected the effect of miR‐129‐5p on hypoxia/reoxygenation (H/R)‐induced H9C2 cell in vitro. MiR‐129‐5p overexpression improved H9C2 cell viability and inhibited cell apoptosis induced by H/R, accompanied with decreased LDH activity and MDA content. Besides, luciferase reporter assay indicated that suppressor of cytokine signaling 2 (SOCS2) was a downstream target of miR‐129‐5p. SOCS2 was upregulated in H/R induced H9C2 cells, and miR‐129‐5p overexpression suppressed SOCS2 expression at both mRNA and protein levels. In addition, SOCS2 overexpression abolished the protective effects of miR‐129‐5p on H/R‐induced H9C2 cells, concomitant with elevated expression of apoptosis‐related cleaved poly‐(ADP‐ribose) polymerase and cleaved caspase‐3. In conclusion, our results demonstrated that miR‐129‐5p alleviated myocardial injury induced by I/R both in vitro and in vivo, and miR‐129‐5p/SOCS2 axis is a potential therapeutic target for alleviating myocardial injury in AMI patients after reperfusion.

Keywords

• ischemia/reperfusion
• miR‐129‐5p
• myocardial injury
• SOCS2