MiR-223-3p as a Novel MicroRNA Regulator of Expression of Voltage-Gated K+ Channel Kv4.2 in Acute Myocardial Infarction

作者：Xue Liu, Ying Zhang, Weijie Du, Haihai Liang, Hua He, Lu Zhang, Zhenwei Pan, Xuelian Li, Chaoqian Xu, Yuhong Zhou, Leimin Wang, Ming Qian, Tianyi Liu, Hongli Yin, Yanjie Lu, Baofeng Yang, Hongli Shan · 发表于：Cellular Physiology and Biochemistry · 年份：2016 · DOI：10.1159/000445609 · 被引用次数：71 · 研究领域：Cardiac electrophysiology and arrhythmias、Ion channel regulation and function、Cardiac Ischemia and Reperfusion

BACKGROUND/AIMS: Acute myocardial infarction (AMI) is a devastating cardiovascular disease with a high rate of morbidity and mortality, partly due to enhanced arrhythmogenicity. MicroRNAs (miRNAs) have been shown to participate in the regulation of cardiac ion channels and the associated arrhythmias. The purpose of this study was to test our hypothesis that miR-223-3p contributes to the electrical disorders in AMI via modulating KCND2, the gene encoding voltage-gated channel Kv4.2 that carries transient outward K+ current Ito. METHODS: AMI model was established in male Sprague-Dawley (SD) rats by left anterior descending artery (LAD) ligation. Evans blue and TTC staining was used to measure infarct area. Ito was recorded in isolated ventricular cardiomyocytes or cultured neonatal rat ventricular cells (NRVCs) by whole-cell patch-clamp techniques. Western blot analysis was employed to detect the protein level of Kv4.2 and real-time RT-PCR to determine the transcript level of miR-223-3p. Luciferase assay was used to examine the interaction between miR-223-3p and KCND2 in cultured NRVCs. RESULTS: Expression of miR-223-3p was remarkably upregulated in AMI relative to sham control rats. On the contrary, the protein level of Kv4.2 and Ito density were significantly decreased in AMI. Consistently, transfection of miR-223-3p mimic markedly reduced Kv4.2 protein level and Ito current in cultured NRVCs. Co-transfection of AMO-223-3p (an antisense inhibitor of miR-223-3p) reversed the r...