Downregulation of cardiac PIASy inhibits Cx43 SUMOylation and ameliorates ventricular arrhythmias in a rat model of myocardial ischemia/reperfusion injury

作     者：Tingting Wang Jinmin Liu Chenchen Hu Xin Wei Linlin Han Afang Zhu Rong Wang Zhijun Chen Zhengyuan Xia Shanglong Yao Weike Mao 

作者机构：Department of AnesthesiologyInstitute of Anesthesiology and Critical Care MedicineUnion HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430022China Department of AnesthesiologyWuhan No.1 HospitalWuhanHubei 430022China State Key Laboratory of Pharmaceutical BiotechnologyDepartment of MedicineThe University of Hong KongHong KongChina 

出 版 物：《Chinese Medical Journal》 (中华医学杂志（英文版）)

年 卷 期：2023年第136卷第11期

页      面：1349-1357页

核心收录：

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

基　　金：National Natural Science Foundation of China(Nos.81770824 and 81470251) 

主　　题：Connexin 43 Myocardial reperfusion injury PIASy PKP2 SUMOylation Arrhythmias 

摘      要：Background:Dysfunction of the gap junction channel protein connexin 43(Cx43)contributes to myocardial ischemia/reperfusion(I/R)-induced ventricular ***43 can be regulated by small ubiquitin-like modifier(SUMO)*** inhibitor of activated STAT Y(PIASy)is an E3 SUMO ligase for its target ***,whether Cx43 is a target protein of PIASy and whether Cx43 SUMOylation plays a role in I/R-induced arrhythmias are largely ***:Male Sprague-Dawley rats were infected with PIASy short hairpin ribonucleic acid(shRNA)using recombinant adeno-associated virus subtype 9(rAAV9).Two weeks later,the rats were subjected to 45 min of left coronary artery occlusion followed by 2 h *** was recorded to assess *** ventricular tissues were collected for molecular biological ***:Following 45 min of ischemia,QRS duration and QTc intervals statistically significantly increased,but these values decreased after transfecting PIASy *** downregulation ameliorated ventricular arrhythmias induced by myocardial I/R,as evidenced by the decreased incidence of ventricular tachycardia and ventricular fibrillation,and reduced arrythmia *** addition,myocardial I/R statistically significantly induced PIASy expression and Cx43 SUMOylation,accompanied by reduced Cx43 phosphorylation and plakophilin 2(PKP2)***,PIASy downregulation remarkably reduced Cx43 SUMOylation,accompanied by increased Cx43 phosphorylation and PKP2 expression after I/***:PIASy downregulation inhibited Cx43 SUMOylation and increased PKP2 expression,thereby improving ventricular arrhythmias in ischemic/reperfused rats heart.