Cardiomyocyte-specific deletion of β-catenin protects mouse hearts from ventricular arrhythmias after myocardial infarction

Abstract Wnt/β-catenin signaling is activated in the heart after myocardial infarction (MI). This study aims to investigate if β-catenin deletion affects post-MI ion channel gene alterations and ventricular tachycardias (VT). MI was induced by permanent ligation of left anterior descending artery in...

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Autores principales:	Jerry Wang, Ying Xia, Aizhu Lu, Hongwei Wang, Darryl R. Davis, Peter Liu, Rob S. Beanlands, Wenbin Liang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5a9f4c209efa4987882e5d18f7648e50
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spelling	oai:doaj.org-article:5a9f4c209efa4987882e5d18f7648e502021-12-02T14:58:47ZCardiomyocyte-specific deletion of β-catenin protects mouse hearts from ventricular arrhythmias after myocardial infarction10.1038/s41598-021-97176-92045-2322https://doaj.org/article/5a9f4c209efa4987882e5d18f7648e502021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-97176-9https://doaj.org/toc/2045-2322Abstract Wnt/β-catenin signaling is activated in the heart after myocardial infarction (MI). This study aims to investigate if β-catenin deletion affects post-MI ion channel gene alterations and ventricular tachycardias (VT). MI was induced by permanent ligation of left anterior descending artery in wild-type (WT) and cardiomyocyte-specific β-catenin knockout (KO) mice. KO mice showed reduced susceptibility to VT (18% vs. 77% in WT) at 8 weeks after MI, associated with reduced scar size and attenuated chamber dilation. qPCR analyses of both myocardial tissues and purified cardiomyocytes demonstrated upregulation of Wnt pathway genes in border and infarct regions after MI, including Wnt ligands (such as Wnt4) and receptors (such as Fzd1 and Fzd2). At 1 week after MI, cardiac sodium channel gene (Scn5a) transcript was reduced in WT but not in KO hearts, consistent with previous studies showing Scn5a inhibition by Wnt/β-catenin signaling. At 8 weeks after MI when Wnt genes have declined, Scn5a returned to near sham levels and K+ channel gene downregulations were not different between WT and KO mice. This study demonstrated that VT susceptibility in the chronic phase after MI is reduced in mice with cardiomyocyte-specific β-catenin deletion primarily through attenuated structural remodeling, but not ion channel gene alterations.Jerry WangYing XiaAizhu LuHongwei WangDarryl R. DavisPeter LiuRob S. BeanlandsWenbin LiangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-18 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jerry Wang Ying Xia Aizhu Lu Hongwei Wang Darryl R. Davis Peter Liu Rob S. Beanlands Wenbin Liang Cardiomyocyte-specific deletion of β-catenin protects mouse hearts from ventricular arrhythmias after myocardial infarction
description	Abstract Wnt/β-catenin signaling is activated in the heart after myocardial infarction (MI). This study aims to investigate if β-catenin deletion affects post-MI ion channel gene alterations and ventricular tachycardias (VT). MI was induced by permanent ligation of left anterior descending artery in wild-type (WT) and cardiomyocyte-specific β-catenin knockout (KO) mice. KO mice showed reduced susceptibility to VT (18% vs. 77% in WT) at 8 weeks after MI, associated with reduced scar size and attenuated chamber dilation. qPCR analyses of both myocardial tissues and purified cardiomyocytes demonstrated upregulation of Wnt pathway genes in border and infarct regions after MI, including Wnt ligands (such as Wnt4) and receptors (such as Fzd1 and Fzd2). At 1 week after MI, cardiac sodium channel gene (Scn5a) transcript was reduced in WT but not in KO hearts, consistent with previous studies showing Scn5a inhibition by Wnt/β-catenin signaling. At 8 weeks after MI when Wnt genes have declined, Scn5a returned to near sham levels and K+ channel gene downregulations were not different between WT and KO mice. This study demonstrated that VT susceptibility in the chronic phase after MI is reduced in mice with cardiomyocyte-specific β-catenin deletion primarily through attenuated structural remodeling, but not ion channel gene alterations.
format	article
author	Jerry Wang Ying Xia Aizhu Lu Hongwei Wang Darryl R. Davis Peter Liu Rob S. Beanlands Wenbin Liang
author_facet	Jerry Wang Ying Xia Aizhu Lu Hongwei Wang Darryl R. Davis Peter Liu Rob S. Beanlands Wenbin Liang
author_sort	Jerry Wang
title	Cardiomyocyte-specific deletion of β-catenin protects mouse hearts from ventricular arrhythmias after myocardial infarction
title_short	Cardiomyocyte-specific deletion of β-catenin protects mouse hearts from ventricular arrhythmias after myocardial infarction
title_full	Cardiomyocyte-specific deletion of β-catenin protects mouse hearts from ventricular arrhythmias after myocardial infarction
title_fullStr	Cardiomyocyte-specific deletion of β-catenin protects mouse hearts from ventricular arrhythmias after myocardial infarction
title_full_unstemmed	Cardiomyocyte-specific deletion of β-catenin protects mouse hearts from ventricular arrhythmias after myocardial infarction
title_sort	cardiomyocyte-specific deletion of β-catenin protects mouse hearts from ventricular arrhythmias after myocardial infarction
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/5a9f4c209efa4987882e5d18f7648e50
work_keys_str_mv	AT jerrywang cardiomyocytespecificdeletionofbcateninprotectsmouseheartsfromventriculararrhythmiasaftermyocardialinfarction AT yingxia cardiomyocytespecificdeletionofbcateninprotectsmouseheartsfromventriculararrhythmiasaftermyocardialinfarction AT aizhulu cardiomyocytespecificdeletionofbcateninprotectsmouseheartsfromventriculararrhythmiasaftermyocardialinfarction AT hongweiwang cardiomyocytespecificdeletionofbcateninprotectsmouseheartsfromventriculararrhythmiasaftermyocardialinfarction AT darrylrdavis cardiomyocytespecificdeletionofbcateninprotectsmouseheartsfromventriculararrhythmiasaftermyocardialinfarction AT peterliu cardiomyocytespecificdeletionofbcateninprotectsmouseheartsfromventriculararrhythmiasaftermyocardialinfarction AT robsbeanlands cardiomyocytespecificdeletionofbcateninprotectsmouseheartsfromventriculararrhythmiasaftermyocardialinfarction AT wenbinliang cardiomyocytespecificdeletionofbcateninprotectsmouseheartsfromventriculararrhythmiasaftermyocardialinfarction
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Cardiomyocyte-specific deletion of β-catenin protects mouse hearts from ventricular arrhythmias after myocardial infarction

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