Yu Wang1, Jian Li2, Liying Xuan1, Yongfeng Liu1, Liqun Shao3, Hongyan Ge4, Junyi Gu3, Chengxi Wei5, Ming Zhao6. 1. Medicinal Chemistry and Pharmacology Institute, Inner Mongolia University for Nationalities, Tongliao, Inner Mongolia, PR China; Inner Mongolia Key Laboratory of Mongolian Medicine Pharmacology for Cardio-Cerebral Vascular System, Tongliao, Inner Mongolia, PR China. 2. Intensive Care Unit, No.2 Affiliated Hospital of Jilin University, ChangChun, Jilin Province, PR China - the emergency and critical care department of the second hospital of Jilin University, Chuangchun, Jilin province, China. 3. Medicinal Chemistry and Pharmacology Institute, Inner Mongolia University for Nationalities, Tongliao, Inner Mongolia, PR China; First Clinical Medical of Inner Mongolia University for Nationalities, Tongliao, Inner Mongolia, PR China. 4. First Clinical Medical of Inner Mongolia University for Nationalities, Tongliao, Inner Mongolia, PR China. 5. Medicinal Chemistry and Pharmacology Institute, Inner Mongolia University for Nationalities, Tongliao, Inner Mongolia, PR China; Inner Mongolia Key Laboratory of Mongolian Medicine Pharmacology for Cardio-Cerebral Vascular System, Tongliao, Inner Mongolia, PR China. Electronic address: weichengxi1224@163.com. 6. Medicinal Chemistry and Pharmacology Institute, Inner Mongolia University for Nationalities, Tongliao, Inner Mongolia, PR China; First Clinical Medical of Inner Mongolia University for Nationalities, Tongliao, Inner Mongolia, PR China; Inner Mongolia Key Laboratory of Mongolian Medicine Pharmacology for Cardio-Cerebral Vascular System, Tongliao, Inner Mongolia, PR China; Affiliated Hospital of Inner Mongolia University for Nationalities, Tongliao, Inner Mongolia, PR China. Electronic address: langzhe73@163.com.
Abstract
BACKGROUND: Viral myocarditis is defined as viral infection of myocardial tissue leading to impaired heart function and heart failure. Accumulating evidences have shown that arrhythmia is one of important complicating diseases of viral myocarditis causing increased mortality and morbidity. There are no effective treatment for the viral infection and complicating arrhythmia. PURPOSE: This study investigated the effect and mechanism of Astragalus Root dry extract (ARDE) on arrhythmia induced by CVB3 in mice. METHODS: The mice and HL-1 cells were treated with CVB3 and ARDE. Reciprocal regulation of Cx43 and miR-1 were observed in the CVB3 infected mouse myocardium and culture HL-1 cells. RESULTS: CVB3 IP injection increased immune cell infiltration in mouse left ventricle and caused irregular arrhythmia. ARDE treatment prevented the increase of immune cell infiltration and arrhythmia. Overexpression of miR-1 significantly inhibited both endogenous Cx43 expression and Cx43 3'UTR luciferase activity in HL-1 cells. Mutation of census binding site of +1586-1593 bp not +465-472 bp in Cx43 3'UTR luciferase resulted in abolishment of miR-1 inhibitory effects in HL-1 cells. Loss-of- function of miR-1 restored CVB3-induced Cx43 expression reduction in cultured HL-1 cells. The presence of ARDE attenuated the augmented miR-1 induced by CVB3 infection in vivo and in vitro. CONCLUSION: This study identified that CVB3 infection reduced Cx43 expression by elevating miR-1 level in mouse viral myocarditis. For the first time, ARDE was shown to prevent arrhythmia, and rescue CVB3-induced endogenous Cx43 expression by regulating miR-1 level.
BACKGROUND:Viral myocarditis is defined as viral infection of myocardial tissue leading to impaired heart function and heart failure. Accumulating evidences have shown that arrhythmia is one of important complicating diseases of viral myocarditis causing increased mortality and morbidity. There are no effective treatment for the viral infection and complicating arrhythmia. PURPOSE: This study investigated the effect and mechanism of Astragalus Root dry extract (ARDE) on arrhythmia induced by CVB3 in mice. METHODS: The mice and HL-1 cells were treated with CVB3 and ARDE. Reciprocal regulation of Cx43 and miR-1 were observed in the CVB3 infected mouse myocardium and culture HL-1 cells. RESULTS: CVB3 IP injection increased immune cell infiltration in mouse left ventricle and caused irregular arrhythmia. ARDE treatment prevented the increase of immune cell infiltration and arrhythmia. Overexpression of miR-1 significantly inhibited both endogenous Cx43 expression and Cx43 3'UTR luciferase activity in HL-1 cells. Mutation of census binding site of +1586-1593 bp not +465-472 bp in Cx43 3'UTR luciferase resulted in abolishment of miR-1 inhibitory effects in HL-1 cells. Loss-of- function of miR-1 restored CVB3-induced Cx43 expression reduction in cultured HL-1 cells. The presence of ARDE attenuated the augmented miR-1 induced by CVB3 infection in vivo and in vitro. CONCLUSION: This study identified that CVB3 infection reduced Cx43 expression by elevating miR-1 level in mouseviral myocarditis. For the first time, ARDE was shown to prevent arrhythmia, and rescue CVB3-induced endogenous Cx43 expression by regulating miR-1 level.
Authors: Stefan Peischard; Huyen Tran Ho; Ilaria Piccini; Nathalie Strutz-Seebohm; Albrecht Röpke; Ivan Liashkovich; Hiteshika Gosain; Bettina Rieger; Karin Klingel; Britta Eggers; Katrin Marcus; Wolfgang A Linke; Frank Ulrich Müller; Stephan Ludwig; Boris Greber; Karin Busch; Guiscard Seebohm Journal: Sci Rep Date: 2020-10-08 Impact factor: 4.379
Authors: Moritz Mirna; Vera Paar; Richard Rezar; Albert Topf; Miriam Eber; Uta C Hoppe; Michael Lichtenauer; Christian Jung Journal: Cells Date: 2019-10-30 Impact factor: 6.600