Enhanced angiogenic capacity and urokinase-type plasminogen activator expression by endothelial cells isolated from human endometrium

The endometrium is a tissue unique for its cyclic destruction and rapid reg eneration of blood vessels. Angiogenesis, indispensable for the regeneratio n process, provides a richly vascularized, receptive endometrium fundamenta l for implantation, placentation, and embryogenesis. Human endometrial micr ovascular endothelial cells (hEMVEC) were isolated to better understand the properties and angiogenic behavior of these cells. Unlike human foreskin m icrovascular endothelial cells (hFMVEC), which proliferated better upon sti mulation by basic fibroblast growth factor, hEMVEC were much more sensitive to vascular endothelial growth factor A (VEGF-A) stimulation, probably due to enhanced VEGF receptor 2 expression. In addition, hEMVEC displayed an e nhanced expression of the urokinase-type plasminogen activator (u-PA) compa red with hFMVEC. No differences were found in tissue-type PA, PA inhibitor- 1, and u-PA receptor expression. The high expression of u-PA by hEMVEC was also found in tissue sections. hEMVEC formed capillary-like structures when cultured in 20% human serum on top of three-dimensional fibrin matrices, a nd VEGF-A or basic fibroblast growth factor increased this tube formation. This is in contrast with hFMVEC, which formed tubes only after simultaneous stimulation by a growth factor and tumor necrosis factor-alpha. The high b asal level of u-PA contributes to and may explain the higher angiogenic pro perties of hEMVEC (in vitro).