Downregulation of miR-483-5p decreases hypoxia-induced injury in human cardiomyocytes by targeting MAPK3.

backgroundMiR-483-5p was recently identified as a risk factor in the early stages of acute myocardial infarction (AMI) patients. Here, we further investigated how miR-483-5p affects cardiomyocyte apoptosis and oxidative stress under hypoxic conditions.

methodsPlasma samples were collected from AMI patients and healthy volunteers. The expression of miR-483-5p was determined using quantitative real-time PCR. An in vitro hypoxic model was constructed to mimic AMI in AC16 cells. Cell viability, apoptosis and oxidative stress biomarker levels (MDA, SOD and CAT) were respectively determined using CCK-8, flow cytometry and commercial assay kits.

resultsThe expression levels of miR-483-5p were significantly higher in AMI patients than in control subjects. Circulating levels of miR-483-5p positively correlated with creatine kinase MB isoform (CK-MB) and cardiac troponin I (cTnI) levels. The in vitro experiments showed that the expression levels of miR-483-5p were also upregulated in hypoxia-induced AC16 cell injury. MiR-483-5p overexpression significantly increased hypoxia-induced cardiomyocyte apoptosis and oxidative stress, while knockdown attenuated these effects. Mechanistically, miR-483-5p directly targets MAPK3 in AC16 cells. Furthermore, the protective effects of miR-483-5p knockdown against hypoxia-induced cardiomyocyte injury are partially dependent on MAPK3.

conclusionsMiR-483-5p, which targets MAPK3, might be a potential therapeutic target for the diagnosis and prevention of hypoxia-induced myocardial injury.