Relationship between prostaglandin E 2 and vascular endothelial growth factor (VEGF) in angiogenesis in human vascular endothelial cells

Abstract

To address the role of prostaglandin E 2 (PGE 2) in tube formation of endothelial cells and the relationships between the action of PGE 2 and vascular endothelial growth factor (VEGF), cultured human umbilical vein endothelial cells (HUVECs) were used to evaluate tube formation on Matrigel and the expression of angiogenesis-related genes. PGE 2 treatment stimulated the tube-like formation of HUVECs. Whereas VEGF-induced tube formation was significantly suppressed by ETYA, an inhibitor of arachidonic acid metabolism, or SU5614, an inhibitor of VEGF-receptor tyrosine kinase, the stimulatory effect of PGE 2 was observed in the presence of ETYA or SU5614. Thus, PGE 2 counteracted both ETYA- and SU5614-induced blockage of angiogenesis in the presence of VEGF. VEGF induced cyclooxygenase (COX) -2 mRNA expression in HUVECs and increased the PGE 2 concentration in the medium. PGE 2 treatment enhanced the expression of VEGF mRNA. These findings suggest that PGE 2 directly stimulates angiogenesis, apart from VEGF signaling, and further induces VEGF expression in HUVECs. In addition, the effect of VEGF on angiogenesis may be mediated, in part, by PGE 2 secretion.