background: Acute myocardial infarction (MI) is a main cause of emergency death in the world. MicroRNAs (miRs/miRNAs) are a series of small non-coding RNA molecules, which regulate cardiovascular disorders that involve MI. In this study, we explored the function of miR-200a in MI treatment.
methods: We observed down-regulation of miR-200a levels and up-regulation of Keap1 and β-catenin levels in HO-treated newborn murine ventricular cardiomyocytes (NMVCs) and the infarcted heart tissues of MI mouse models, compared to the non-treated NMVCs and normal heart tissues of healthy mice.
results: CCK-8 and colony formation assays indicated the reduction in NMVC vitality due to HO treatment and the recovery of cell vi... More
background: Acute myocardial infarction (MI) is a main cause of emergency death in the world. MicroRNAs (miRs/miRNAs) are a series of small non-coding RNA molecules, which regulate cardiovascular disorders that involve MI. In this study, we explored the function of miR-200a in MI treatment.
methods: We observed down-regulation of miR-200a levels and up-regulation of Keap1 and β-catenin levels in HO-treated newborn murine ventricular cardiomyocytes (NMVCs) and the infarcted heart tissues of MI mouse models, compared to the non-treated NMVCs and normal heart tissues of healthy mice.
results: CCK-8 and colony formation assays indicated the reduction in NMVC vitality due to HO treatment and the recovery of cell vitality due to miR-200a overexpression, respectively. Flow cytometry with Annexin and PI staining indicated the inhibition of HO-triggered cell apoptosis through ectopically expressed miR-200a. Western blotting and ELISA analyses that detected pro-inflammatory cell factors [interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α] confirmed that miR-200a prevented HO-induced NMVC inflammation. Moreover, miR-200a inhibited up-regulation of Keap1 and β-catenin expression in HO-treated NMVCs by directly binding with the 3'-UTR regions of both Keap1 and β-catenin. Furthermore, overexpression of Keap1 and β-cateninin in HO-treated NMVCs with recovered miR-200a elevated inflammation and apoptosis, respectively.
conclusions: The results showed that miR-200a expression was inhibited in murine cardiomyocytes due to HO stress in MI cardiac tissues and overexpressed miR-200a could protect the cells from death by regulating the Keap1/Nrf2 and β-catenin signal transduction pathways.
