ere Paavola, Tarja Alakoski, Johanna Ulvila, Teemu Kilpiö, Juuso Sirén, Sanni Perttunen, Suneeta Narumanchi, Hong Wang, Ruizhu Lin, Katja Porvari, Juhani Junttila, Heikki Huikuri, Katariina Immonen, Päivi Lakkisto, Johanna Magga, Ilkka Tikkanen, Risto Kerkelä, Vezf1 regulates cardiac structure and contractile function, EBioMedicine, Volume 51, 2020, 102608, ISSN 2352-3964, https://doi.org/10.1016/j.ebiom.2019.102608
Vezf1 regulates cardiac structure and contractile function
|Author:||Paavola, Jere1; Alakoski, Tarja2; Ulvila, Johanna2;|
1Unit of Cardiovascular Research, Minerva Foundation Institute for Medical Research, Helsinki, Finland
2Research Unit of Biomedicine, Department of Pharmacology and Toxicology, University of Oulu, Finland
3Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
4Department of Forensic Medicine, Research Unit of Internal Medicine, University of Oulu, Oulu, Finland
5Division of Cardiology, Research Unit of Internal Medicine, University of Oulu and Oulu University Hospital, Oulu, Finland
6Clinical Chemistry and Hematology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
7Abdominal Center, Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
|Online Access:||PDF Full Text (PDF, 1.9 MB)|
|Persistent link:|| http://urn.fi/urn:nbn:fi-fe2020042822803
|Publish Date:|| 2020-04-28
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.
|Type of Publication:||
A1 Journal article – refereed
|Field of Science:||
This work was supported by research funding of the Helsinki-Uusimaa Hospital District (state funding for university-level health research) (to I.T.) and by grants from the Academy of Finland (grant N:o to 256908 J.U., grant N:o 268505 to J.M. and grant N:o 297094 to R.K.), Jane and Aatos Erkko Foundation (to R.K and H.H.), Aarne Koskelo Foundation (to J.P., S.N. and I.T.), the Finnish Foundation for Cardiovascular Research (to J.P., J.U., T.A., I.T. and R.K.), the Finnish Cultural Foundation (to T.A., S.N. and H.W.), the Finnish Foundation for Laboratory Medicine (to P.L.), the Finska Läkaresällskapet (to I.T.) and the Liv och Hälsa Foundation (to I.T.).
|Academy of Finland Grant Number:||
268505 (Academy of Finland Funding decision)
297094 (Academy of Finland Funding decision)
256908 (Academy of Finland Funding decision)
© 2019 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license. (http://creativecommons.org/licenses/by-nc-nd/4.0/).