Vezf1 regulates cardiac structure and contractile function.

Autor:	Paavola J; Unit of Cardiovascular Research, Minerva Foundation Institute for Medical Research, Helsinki, Finland., Alakoski T; Research Unit of Biomedicine, Department of Pharmacology and Toxicology, University of Oulu, Finland., Ulvila J; Research Unit of Biomedicine, Department of Pharmacology and Toxicology, University of Oulu, Finland., Kilpiö T; Research Unit of Biomedicine, Department of Pharmacology and Toxicology, University of Oulu, Finland; Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland., Sirén J; Unit of Cardiovascular Research, Minerva Foundation Institute for Medical Research, Helsinki, Finland., Perttunen S; Unit of Cardiovascular Research, Minerva Foundation Institute for Medical Research, Helsinki, Finland., Narumanchi S; Unit of Cardiovascular Research, Minerva Foundation Institute for Medical Research, Helsinki, Finland., Wang H; Unit of Cardiovascular Research, Minerva Foundation Institute for Medical Research, Helsinki, Finland., Lin R; Research Unit of Biomedicine, Department of Pharmacology and Toxicology, University of Oulu, Finland; Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland., Porvari K; Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland; Department of Forensic Medicine, Research Unit of Internal Medicine, University of Oulu, Oulu, Finland., Junttila J; Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland; Division of Cardiology, Research Unit of Internal Medicine, University of Oulu and Oulu University Hospital, Oulu, Finland., Huikuri H; Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland; Division of Cardiology, Research Unit of Internal Medicine, University of Oulu and Oulu University Hospital, Oulu, Finland., Immonen K; Unit of Cardiovascular Research, Minerva Foundation Institute for Medical Research, Helsinki, Finland., Lakkisto P; Unit of Cardiovascular Research, Minerva Foundation Institute for Medical Research, Helsinki, Finland; Clinical Chemistry and Hematology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland., Magga J; Research Unit of Biomedicine, Department of Pharmacology and Toxicology, University of Oulu, Finland., Tikkanen I; Unit of Cardiovascular Research, Minerva Foundation Institute for Medical Research, Helsinki, Finland; Abdominal Center, Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland., Kerkelä R; Research Unit of Biomedicine, Department of Pharmacology and Toxicology, University of Oulu, Finland; Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland. Electronic address: Risto.Kerkela@oulu.fi.
Jazyk:	angličtina
Zdroj:	EBioMedicine [EBioMedicine] 2020 Jan; Vol. 51, pp. 102608. Date of Electronic Publication: 2020 Jan 03.
DOI:	10.1016/j.ebiom.2019.102608
Abstrakt:	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 Ca 2+ 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. Competing Interests: Declaration of Competing Interest The authors have nothing to disclose. (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze:	MEDLINE
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