PUBLICATION
Vezf1 regulates cardiac structure and contractile function
- Authors
- 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.
- ID
- ZDB-PUB-200109-4
- Date
- 2020
- Source
- EBioMedicine 51: 102608 (Journal)
- Registered Authors
- Keywords
- Cardiac contractile function, Cardiac hypertrophy, TEAD-1, Vezf1
- MeSH Terms
-
- Adrenergic Agents/pharmacology
- Animals
- Binding Sites
- Cardiomyopathies/genetics
- DNA-Binding Proteins/metabolism*
- Gene Expression Regulation/drug effects
- Genes, Reporter
- Humans
- Luciferases/metabolism
- Mice, Inbred C57BL
- Myocardial Contraction*
- Myocardium/metabolism*
- Myocardium/pathology*
- Myocytes, Cardiac/drug effects
- Myocytes, Cardiac/metabolism
- Myosin Heavy Chains/genetics
- Myosin Heavy Chains/metabolism
- Neovascularization, Physiologic/drug effects
- Promoter Regions, Genetic/genetics
- Protein Binding/drug effects
- Rats, Sprague-Dawley
- Transcription Factors/metabolism*
- Zebrafish
- Zebrafish Proteins/metabolism*
- PubMed
- 31911272 Full text @ EBioMedicine
Citation
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. 51:102608.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping