Overexpression of miR-375 Protects Cardiomyocyte Injury following Hypoxic-Reoxygenation Injury

• Published in: Oxidative medicine and cellular longevity Vol. 2020; no. 2020; pp. 1 - 10
• Main Author: Sayed, Ali Sheikh Md
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Publishing Corporation 2020; Hindawi; John Wiley & Sons, Inc; Hindawi Limited
• Subjects: Analysis; Angina pectoris; Apoptosis; Biomarkers; Cardiomyocytes; Coronary vessels; Ethylenediaminetetraacetic acid; Gene expression; Heart attack; Heart attacks; Heart failure; Hospitals; Hypoxia; Kinases; MicroRNA; MicroRNAs; Pain; Proteins; Studies; Tenecteplase; Veins & arteries; China
• ISSN: 1942-0900; 1942-0994
• DOI: 10.1155/2020/7164069

The aim of the study was to evaluate the clinical significance of microRNA-375 in acute myocardial infarction patients and its mimic action in hypoxia/reoxygenation- (H/R-) induced ventricular cardiomyocyte H9c2 injury. In the current study, 90 ST-elevated acute MI patients (STEMI), 75 non-ST-elevated acute MI patients (NSTEMI), 90 healthy subjects, 14 weeks old mice, and ventricular cardiomyocyte H9c2 were included. The expressions of plasma microRNA-375 in patients with STEMI and NSTEMI and AMI mouse models were remarkably decreased than in controls (P<0.001). The areas under the curve (AUC) of plasma microRNA-375 were revealed 0.939 in STEMI and 0.935 in NSTEMI subjects. Moreover, microRNA-375 levels in H/R-exposed cardiac H9c2 cells were evidently downregulated and significantly increased apoptosis rate and caspase-3 activity levels, while overexpression of miR-375 remarkably reduced apoptosis percentage and caspase-3 levels as compared with normal cells. Furthermore, this study also demonstrated that Nemo-like kinase (NLK), NLK mRNA, and protein expression levels were significantly downregulated in H/R-injured H9c2 cells, on the contrary, H9c2 cells transfected with mimic-miR-375 greatly upregulated NLK mRNA and protein expression. Plasma microRNA-375 may serve as an essential clinical biomarker for diagnosis of early-stage AMI. Mimic expression of miR-375 significantly prevented H/R-induced cardiomyocyte injury by decreasing caspase-3 activity through upregulation of the NLK gene, recommended as a new therapeutic option for AMI patient.