Relationship between prostaglandin E2 and vascular endothelial growth factor (VEGF) in angiogenesis in human vascular endothelial cells

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. (c) 2006 Elsevier Inc. All rights reserved.