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.

中文翻译：

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Vezf1调节心脏结构和收缩功能。

背景技术血管内皮锌指1（Vezf1）是先前显示出调节血管生成和血管生成的转录因子。我们旨在调查Vezf1在产后心脏中的作用。方法在斑马鱼和原代心肌细胞中研究了Vezf1在调节心脏生长和收缩功能中的作用。结果我们发现在患病的人心肌和小鼠心脏中Vezf1的表达降低。我们的实验数据表明，斑马鱼Vezf1的敲低会降低心脏的生长，并导致对β-肾上腺素刺激的心室收缩反应受损。但是，Vezf1基因敲低与心肌细胞Ca2 +瞬态动力学失调有关。基因本体富集分析表明，Vezf1调节心肌收缩和扩张的心肌病相关基因，我们确定心肌细胞Myh7 /β-MHC为Vezf1的关键靶标。我们进一步确定在调节对Vezf1敲低的响应的Myh7启动子中MCAT结合位点的关键作用，并显示TEAD-1是Vezf1的结合伴侣。解释我们证明了Vezf1在调节代偿性心脏生长和心肌收缩功能中的作用，这可能与人类心脏疾病有关。