Endothelial cell mineralocorticoid receptors oppose VEGF-induced gene expression and angiogenesis.

Aldosterone is a key factor in adverse cardiovascular remodeling by acting on the mineralocorticoid receptor (MR) in different cell types. Endothelial MR activation mediates hypertrophy, inflammation and fibrosis. Cardiovascular remodeling is often accompanied by impaired angiogenesis, which is a risk factor for the development of heart failure.

Extracellular bone morphogenetic protein modulator BMPER and twisted gastrulation homolog 1 preserve arterial-venous specification in zebrafish blood vessel development and regulate Notch signaling in endothelial cells.

The bone morphogenetic protein (BMP) signaling pathway plays a central role during vasculature development. Mutations or dysregulation of the BMP pathway members have been linked to arteriovenous malformations. In the present study, we investigated the effect of the BMP modulators bone morphogenetic protein endothelial precursor-derived regulator (BMPER) and twisted gastrulation protein homolog 1 (TWSG1) on arteriovenous specification during zebrafish development and analyzed downstream Notch signaling pathway in human endothelial cells.

The neuronal transcription factor NPAS4 is a strong inducer of sprouting angiogenesis and tip cell formation.

Rationale: Regarding branching morphogenesis, neurogenesis and angiogenesis share common principle mechanisms and make use of the same molecules. Therefore, the investigation of neuronal molecules involved in vascular morphogenesis provides new possibilities for pro-angiogenic approaches in cardiovascular diseases.

Objective: In this study, we investigated the role of the neuronal transcription factor NPAS4 in angiogenesis.