Vezf1 regulates cardiac structure and contractile function

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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 .

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 organization: Medicum
Department of Clinical Chemistry and Hematology
University of Helsinki
Department of Medicine
HUS Abdominal Center
Nefrologian yksikkö
Date: 2020-01
Language: eng
Number of pages: 12
Belongs to series: EBioMedicine
ISSN: 2352-3964
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
Cardiac hypertrophy
Cardiac contractile function
3121 General medicine, internal medicine and other clinical medicine
Peer reviewed: Yes
Rights: cc_by_nc_nd
Usage restriction: openAccess
Self-archived version: publishedVersion

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