Meteorin-Like (METRNL) Attenuates Myocardial Ischemia/Reperfusion Injury-Induced Cardiomyocytes Apoptosis by Alleviating Endoplasmic Reticulum Stress via Activation of AMPK-PAK2 Signaling in H9C2 Cells.

BACKGROUND Myocardial ischemia mediates the progression of multiple cardiovascular diseases and leads to serious damage to the morphology, function, and metabolism of cardiomyocytes. The serum level of the hormone Meteorin-like (METRNL) was lower in patients with coronary artery disease and was negatively correlated with inflammatory cytokines. The aim of the present study was to determine the relationship between METRNL and myocardial ischemia/reperfusion (MI/R) injury, and investigate the molecular mechanisms implicated the pathogenesis of myocardial ischemia. MATERIAL AND METHODS In the present study, H9C2 cells underwent oxygen-glucose deprivation and reperfusion (OGD/R) treatment to establish a MI/R cell model. Quantitative real-time polymerase chain reaction was performed to analyze the expression of target gene. Western blot was used to evaluate the protein expression. Cell Counting Kit-8 assay was employed to detect the cell viability. Enzyme-linked immunosorbent assay was carried out to determine the levels of inflammatory cytokines. Finally, flow cytometry and TUNEL staining were used to detect the apoptotic levels of cardiomyocytes. RESULTS The results showed that the expression of METRNL was downregulated in H9C2 cells during OGD/R. Interestingly, METRNL overexpression inhibited the inflammation, apoptosis and endoplasmic reticulum stress in H9C2 cells during OGD/R, which were totally reversed by PAK2 silencing. In addition, METRNL overexpression induced activation of AMPK-PAK2 signaling cascade. CONCLUSIONS METRNL attenuates MI/R injury-induced cardiomyocytes apoptosis by alleviating endoplasmic reticulum stress via activation of AMPK-PAK2 signaling in H9C2 cells. Our findings support that METRNL might be a promising target for treatment of myocardial ischemia in the future.