Vezf1 regulates cardiac structure and contractile function
| Autor: | Juhani Junttila, Tarja Alakoski, Päivi Lakkisto, Risto Kerkelä, Ruizhu Lin, Johanna Magga, Johanna Ulvila, Sanni Perttunen, Heikki V. Huikuri, Jere Paavola, Ilkka Tikkanen, Hong Wang, Katariina Immonen, Teemu Kilpiö, Suneeta Narumanchi, Katja Porvari, Juuso Siren |
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| Přispěvatelé: | Medicum, HUSLAB, Department of Clinical Chemistry and Hematology, University of Helsinki, Department of Medicine, HUS Abdominal Center, Clinicum, Nefrologian yksikkö |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Research paper Angiogenesis lcsh:Medicine Vascular endothelial zinc finger 1 ANGIOGENESIS Rats Sprague-Dawley 0302 clinical medicine Genes Reporter TEAD-1 Myocytes Cardiac TRANSCRIPTION FACTOR Cardiac contractile function Luciferases Promoter Regions Genetic Zebrafish lcsh:R5-920 Gene knockdown ROLES biology Dilated cardiomyopathy General Medicine Cell biology DNA-Binding Proteins Cardiac hypertrophy Vezf1 030220 oncology & carcinogenesis GROWTH lcsh:Medicine (General) Cardiomyopathies Protein Binding EXPRESSION Neovascularization Physiologic REQUIREMENT General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Adrenergic Agents Vasculogenesis medicine Animals Humans Transcription factor Binding Sites Myosin Heavy Chains ZEBRAFISH Myocardium lcsh:R Zebrafish Proteins PERFORMANCE medicine.disease biology.organism_classification Myocardial Contraction ENDOTHELIAL-CELLS Mice Inbred C57BL HYPERTROPHY 030104 developmental biology Gene Expression Regulation 3121 General medicine internal medicine and other clinical medicine MYH7 3111 Biomedicine Transcription Factors |
| Zdroj: | EBioMedicine EBioMedicine, Vol 51, Iss, Pp-(2020) |
| Popis: | 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. Keywords: Vezf1, Cardiac hypertrophy, Cardiac contractile function, TEAD-1 |
| Databáze: | OpenAIRE |
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