Vezf1 regulates cardiac structure and contractile function

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http://hdl.handle.net/10138/313484

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Paavola , J , Alakoski , T , Ulvila , J , Kilpiö , T , Sirén , J , Perttunen , S , Narumanchi , S , Wang , H , Lin , R , Porvari , K , Junttila , J , Huikuri , H , Immonen , K , Lakkisto , P , Magga , J , Tikkanen , I & Kerkelä , R 2020 , ' Vezf1 regulates cardiac structure and contractile function ' , EBioMedicine , vol. 51 , 102608 . https://doi.org/10.1016/j.ebiom.2019.102608

Title: Vezf1 regulates cardiac structure and contractile function
Author: Paavola, Jere; Alakoski, Tarja; Ulvila, Johanna; Kilpiö, Teemu; Sirén, Juuso; Perttunen, Sanni; Narumanchi, Suneeta; Wang, Hong; Lin, Ruizhu; Porvari, Katja; Junttila, Juhani; Huikuri, Heikki; Immonen, Katariina; Lakkisto, Päivi; Magga, Johanna; Tikkanen, Ilkka; Kerkelä, Risto
Contributor: University of Helsinki, Minerva Foundation Institute for Medical Research
University of Helsinki, Minerva Foundation Institute for Medical Research
University of Helsinki, Medicum
University of Helsinki, Minerva Foundation Institute for Medical Research
University of Helsinki, HUSLAB
University of Helsinki, Department of Medicine
Date: 2020-01
Language: eng
Number of pages: 12
Belongs to series: EBioMedicine
ISSN: 2352-3964
URI: http://hdl.handle.net/10138/313484
Abstract: Background Vascular endothelial zinc finger 1 (Vezf1) is a transcription factor previously shown to regulate vasculogenesis and angiogenesis. We aimed to investigate the role of Vezf1 in the postnatal heart. Methods The role of Vezf1 in regulating cardiac growth and contractile function was studied in zebrafish and in primary cardiomyocytes. Findings We find that expression of Vezf1 is decreased in diseased human myocardium and mouse hearts. Our experimental data shows that knockdown of zebrafish Vezf1 reduces cardiac growth and results in impaired ventricular contractile response to β-adrenergic stimuli. However, Vezf1 knockdown is not associated with dysregulation of cardiomyocyte Ca2+ transient kinetics. Gene ontology enrichment analysis indicates that Vezf1 regulates cardiac muscle contraction and dilated cardiomyopathy related genes and we identify cardiomyocyte Myh7/β-MHC as key target for Vezf1. We further identify a key role for an MCAT binding site in the Myh7 promoter regulating the response to Vezf1 knockdown and show that TEAD-1 is a binding partner of Vezf1. Interpretation We demonstrate a role for Vezf1 in regulation of compensatory cardiac growth and cardiomyocyte contractile function, which may be relevant in human cardiac disease.
Subject: 3111 Biomedicine
Vezf1
Cardiac hypertrophy
Cardiac contractile function
TEAD-1
ZEBRAFISH
ANGIOGENESIS
PERFORMANCE
HYPERTROPHY
ROLES
ENDOTHELIAL-CELLS
GROWTH
TRANSCRIPTION FACTOR
EXPRESSION
REQUIREMENT
3121 General medicine, internal medicine and other clinical medicine
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