miR-194-5p protects against myocardial ischemia/reperfusion injury via MAPK1/PTEN/AKT pathway.

BACKGROUND

MicroRNA (miRNA), which participates in various physiological and pathological processes, is a highly conserved small RNA sequence. This study aimed to investigate the role of miR-194-5p in hypoxia/reoxygenation (H/R)-induced cardiomyocyte apoptosis and myocardial ischemia/reperfusion (I/R) injury.

METHODS

We set up an H/R H9c2 cell model and an I/R mouse model . Then, cell vitality, apoptosis, and histopathological evaluation were conducted. Reactive oxygen species (ROS) generation and the activity of superoxide dismutase (SOD) and malondialdehyde (MDA) were examined by 2',7'-Dichlorodihydrofluorescein diacetate (H2DCFDA), and enzyme-linked immunosorbent assay (ELISA), respectively. The level of creatine kinase isoenzyme (CK-MB), cardiac troponin I (cTnI), myoglobin (Mb) is examined by ELISA. The expression of Caspase-3, cleaved-Caspase-3, Bax, Bcl-2, phosphatase and tensin homolog deleted on chromosome ten (PTEN), and protein kinase B (AKT) was analyzed by western blot.

RESULTS

Data showed the expression of miR-194-5p was decreased in H/R-induced H9c2 cells and I/R-induced mouse. Conversely, overexpression of miR-194-5p could improve cardiomyocyte damage in ischemic models and . Furthermore, mitogen-activated protein kinase 1 (MAPK1) was found as a direct target of miR-194-5p, which negatively regulated the expression of MAPK1. The up-regulation of MAPK1 inhibited the myocardial protection previously observed by miR-194-5p.

CONCLUSIONS

Our study shows overexpression of miR-194-5p protects against H/R injury and cardiac I/R injury , which involves the inhibition of cardiac apoptosis and oxidative stress by targeting MAPK1 expression via PTEN/AKT pathway. These findings supply novel insights into potential therapeutic targets for cardiovascular diseases.