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http://purl.uniprot.org/citations/31125668http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/31125668http://www.w3.org/2000/01/rdf-schema#comment"

Background

β-Catenin/T-cell factor 4 (TCF4) signaling is enhanced in ischemic heart disease in which ventricular tachycardia (VT)/ventricular fibrillation occurs frequently. How this signaling links to arrhythmogenesis remains unclear.

Objective

The purpose of this study was to investigate the role of β-catenin gain of function in the development of arrhythmia.

Methods

A mouse model with a conditional deletion of CTNNB1 exon 3 resulting in cardiac exon 3-deleted and stabilized β-catenin (β-catΔE3) was used to determine the role of β-catenin gain of function in the regulation of cardiac rhythm.

Results

Western blotting showed β-catΔE3 expression and significantly decreased NaV1.5 protein in CTNNB1 E3-/- and CTNNB1 E3+/- mouse hearts. Real-time qRT-PCR revealed significantly decreased NaV1.5 messenger RNA with no changes in Na+ channel β1 to β4 expression in these hearts. Immunofluorescence revealed accumulation of β-catΔE3 in the nuclei of CTNNB1 E3-/- cardiomyocytes. Immunohistochemistry demonstrated nuclear localization of β-catenin in cardiomyocytes, which was associated with significantly decreased NaV1.5 messenger RNA in human ischemic hearts. Immunoprecipitation revealed that β-catΔE3 interacted with TCF4 in CTNNB1 E3-/- cardiomyocytes. Whole-cell recordings showed that Na+ currents and depolarization and amplitude of action potentials were significantly decreased in CTNNB1 E3-/- ventricular myocytes. Electrocardiographic recordings demonstrated that in mice with cardiac CTNNB1 E3-/-, the QRS complex was prolonged and VT was induced by the Na+ channel blocker flecainide. However, cardiac function, as determined by echocardiography and heart/body weight ratios, remained unchanged.

Conclusion

Enhancement of β-catenin/TCF4 signaling led to the prolongation of the QRS complex and increase in susceptibility to VT by suppression of NaV1.5 expression and Na+ channel activity in mice."xsd:string
http://purl.uniprot.org/citations/31125668http://purl.org/dc/terms/identifier"doi:10.1016/j.hrthm.2019.05.015"xsd:string
http://purl.uniprot.org/citations/31125668http://purl.uniprot.org/core/author"Li F."xsd:string
http://purl.uniprot.org/citations/31125668http://purl.uniprot.org/core/author"Lu Y."xsd:string
http://purl.uniprot.org/citations/31125668http://purl.uniprot.org/core/author"Sun L."xsd:string
http://purl.uniprot.org/citations/31125668http://purl.uniprot.org/core/author"Xu H."xsd:string
http://purl.uniprot.org/citations/31125668http://purl.uniprot.org/core/author"Zhao L."xsd:string
http://purl.uniprot.org/citations/31125668http://purl.uniprot.org/core/author"Ye B."xsd:string
http://purl.uniprot.org/citations/31125668http://purl.uniprot.org/core/author"Wang N."xsd:string
http://purl.uniprot.org/citations/31125668http://purl.uniprot.org/core/author"Hu C."xsd:string
http://purl.uniprot.org/citations/31125668http://purl.uniprot.org/core/author"Huo R."xsd:string
http://purl.uniprot.org/citations/31125668http://purl.uniprot.org/core/author"Deb A."xsd:string
http://purl.uniprot.org/citations/31125668http://purl.uniprot.org/core/date"2019"xsd:gYear
http://purl.uniprot.org/citations/31125668http://purl.uniprot.org/core/name"Heart Rhythm"xsd:string
http://purl.uniprot.org/citations/31125668http://purl.uniprot.org/core/pages"1720-1728"xsd:string
http://purl.uniprot.org/citations/31125668http://purl.uniprot.org/core/title"Enhancement of beta-catenin/T-cell factor 4 signaling causes susceptibility to cardiac arrhythmia by suppressing Napisub>Vpi/sub>1.5 expression in mice."xsd:string
http://purl.uniprot.org/citations/31125668http://purl.uniprot.org/core/volume"16"xsd:string
http://purl.uniprot.org/citations/31125668http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/31125668
http://purl.uniprot.org/citations/31125668http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/31125668
http://purl.uniprot.org/uniprot/#_D3Z7S6-mappedCitation-31125668http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/31125668
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