Myocardial ischemia-reperfusion(I/R)injury is a pathological process characterized by cardiomyocyte apoptosis,which leads to cardiac dysfunction.Increasing evidence shows that abnormal expression of long noncoding RNAs(IncRNAs)plays a crucial role in cardiovascular diseases.In this study we investigated the role of IncRNAs in myocardial l/R injury.Myocardial I/R injury was induced in mice by ligating left anterior descending coronary artery for 45 min followed by reperfusion for 24 h.We showed that IncRNA KnowTID_00006395,termed IncRNA-6395 was significantly upregulated in the infarct area of mouse hearts following I/R injury as well as in H2O2-treated neonatal mouse ventricular cardiomyocytes(NMVCs).Overexpression of IncRNA-6395 led to cell apoptosis and the expression change of apoptosis-related proteins in NMVCs,whereas knockdown of lncRNA-6395 attenuated H2O2-induced cell apoptosis.LncRNA-6395 knockout mice(IncRNA-6395+/-)displayed improved cardiac function,decreased plasma LDH activity and infarct size following I/R injury.We demonstrated that IncRNA-6395 directly bound to p53,and increased the abundance of p53 protein through inhibiting ubiquitination-mediated p53 degradation and thereby facilitated p53 translocation to the nucleus.More importantly,overexpression of p53 canceled the inhibitory effects of IncRNA-6395 knockdown on cardiomyocyte apoptosis,whereas knockdown of p53 counteracted the apoptotic effects of lncRNA-6395 in cardiomyocytes.Taken together,IncRNA-6395 as an endogenous pro-apoptotic factor,regulates cardiomyocyte apoptosis and myocardial l/R injury by inhibiting degradation and promoting sub-cellular translocation of p53.

Lin-feng Zhan;Qi Zhang;Lu Zhao;Xue Dong;Xin-yu Pei;Li-Ii Peng;Xiao-wen Zhang;Bo Meng;Wen-di Shang;Zhen-wei Pan;Chao-qian Xu;Yan-jie Lu;Ming-yu Zhang

Department of Pharmacology(State-Province Key Laboratories of Biomedicine-Pharmaceutics of China,Key Laboratory of Cardiovascular Medicine Research,Ministry of Education),College of Pharmacy,Harbin Medical University,Harbin 150081,China;China Northern Translational Medicine Research and Cooperation Center,Heilongjiang Academy of Medical Sciences,Harbin Medical University,Harbin 150081,China

中国药理学报（英文版）

[1]Lin-feng Zhan;Qi Zhang;Lu Zhao;Xue Dong;Xin-yu Pei;Li-Ii Peng;Xiao-wen Zhang;Bo Meng;Wen-di Shang;Zhen-wei Pan;Chao-qian Xu;Yan-jie Lu;Ming-yu Zhang-.LncRNA-6395 promotes myocardial ischemia-reperfusion injury in mice through increasing p53 pathway)[J].中国药理学报（英文版）,2022(06):1383-1394

KnowTID,6395+

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