Up-regulated novel-miR-17 promotes hypothermic reperfusion arrhythmias by negatively targeting Gja1 and mediating activation of the PKC/c-Jun signaling pathway

• Published in: Journal of molecular and cellular cardiology 2024-08, Vol.193, p.1-10
• Main Authors: Yi, Jing, Chen, Kaiyuan, Cao, Ying, Wen, Chunlei, An, Li, Tong, Rui, Wu, Xueyan, Gao, Hong
• Format: Article
• Language: English
• Subjects: Arrhythmia; Gja1; Hypothermia; Ischemia-reperfusion; Novel-miR-17; PKC/c-Jun signaling pathway
• ISSN: 0022-2828; 1095-8584; 1095-8584
• DOI: 10.1016/j.yjmcc.2024.05.009

Hypothermic ischemia-reperfusion arrhythmia is a common complication of cardiothoracic surgery under cardiopulmonary bypass, but few studies have focused on this type of arrhythmia. Our prior study discovered reduced myocardial Cx43 protein levels may be linked to hypothermic reperfusion arrhythmias. However, more detailed molecular mechanism research is required. The microRNA and mRNA expression levels in myocardial tissues were detected by real-time quantitative PCR (RT-qPCR). Besides, the occurrence of hypothermic reperfusion arrhythmias and changes in myocardial electrical conduction were assessed by electrocardiography and ventricular epicardial activation mapping. Furthermore, bioinformatics analysis, applying antagonists of miRNA, western blotting, immunohistochemistry, a dual luciferase assay, and pearson correlation analysis were performed to investigate the underlying molecular mechanisms. The expression level of novel-miR-17 was up-regulated in hypothermic ischemia-reperfusion myocardial tissues. Inhibition of novel-miR-17 upregulation ameliorated cardiomyocyte edema, reduced apoptosis, increased myocardial electrical conduction velocity, and shortened the duration of reperfusion arrhythmias. Mechanistic studies showed that novel-miR-17 reduced the expression of Cx43 by directly targeting Gja1 while mediating the activation of the PKC/c-Jun signaling pathway. Up-regulated novel-miR-17 is a newly discovered pro-arrhythmic microRNA that may serve as a potential therapeutic target and biomarker for hypothermic reperfusion arrhythmias. [Display omitted] •Upregulated novel-miR-17 aggravates myocardial hypothermic ischemia-reperfusion injury.•novel-miR-17 reduces electrical conduction velocity by targeting Gja1.•PKC/c-Jun signaling pathway activation in hypothermia reperfusion arrhythmia.•novel-miR-17 mediates the activation of the PKC/c-Jun signaling pathway.