Vezf1 regulates cardiac structure and contractile function
Jere Paavola, Tarja Alakoski, Johanna Ulvila, Teemu Kilpiö, Juuso Sirén, Sanni Perttunen, Suneeta Narumanchi, Hong Wang, Ruizhu Lin, Katja Porvari, Juhani Junttila, Heikki V. Huikuri, Katariina Immonen, Päivi Lakkisto, Johanna Magga, Ilkka Tikkanen, Risto Kerkelä
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: 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.