A novel regulatory function of proteolytically cleaved VEGF-2 for vascular endothelial and smooth muscle cells

By high throughput sequencing, we have identified a cDNA encoding a polypeptide related to vascular endothelial growth factor (VEGF) and placenta growth factor (PlGF) in the VEGF/PDGF gene family. It is designated vascular endothelial growth factor 2 (VEGF-2). Similar to VEGF, expression of VEGF-2 mRNA is abundant in vascular smooth muscle cells and several highly vascularized tissues. VEGF-2 protein is expressed as a secreted 52 kDa precursor as well as the 30 kDa amino-terminal and 27 kDa carboxy-terminal cleavage products. The latter two cleavage products are linked via a disulfide bridge (or bridges) and can be copurified. Using copurified 30 and 27 kDa proteins, the effect of VEGF-2 on growth of several cell types, including vascular endothelial and smooth muscle cells, was determined. Our results demonstrate that VEGF-2 protein stimulates the growth of human vascular endothelial cells but inhibits growth of human aortic smooth muscle cells induced by platelet-derived growth factor. These studies establish VEGF-2 as a novel regulator for growth of vascular endothelial and smooth muscle cells.