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Enhanced Angiogenic Capacity and Urokinase-Type Plasminogen Activator Expression by Endothelial Cells Isolated from Human Endometrium

Gaubius Laboratory TNO-PG (P.K., K.K., B.M., E.v.S., B.v.d.V., V.W.M.v.H.), 2333 CK Leiden, The Netherlands; Department of Obstetrics, Gynecology, and Reproductive Medicine, Leiden University Medical Center (K.K., B.M., E.v.S., F.M.H.), 2300 CK Leiden, The Netherlands; and Department of Physiology, Institute for Cardiovascular Research, Vrije Universiteit (V.W.M.v.H.), 1081 BT Amsterdam, The Netherlands

Address all correspondence and requests for reprints to: Dr. P. Koolwijk, Gaubius Laboratory TNO-PG, Zernikedreef 9, 2333 CK Leiden, The Netherlands. E-mail: p.koolwijk{at}pg.tno.nl

Abstract

The endometrium is a tissue unique for its cyclic destruction and rapid regeneration of blood vessels. Angiogenesis, indispensable for the regeneration process, provides a richly vascularized, receptive endometrium fundamental for implantation, placentation, and embryogenesis. Human endometrial microvascular endothelial cells (hEMVEC) were isolated to better understand the properties and angiogenic behavior of these cells. Unlike human foreskin microvascular endothelial cells (hFMVEC), which proliferated better upon stimulation 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 enhanced expression of the urokinase-type plasminogen activator (u-PA) compared 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, and 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-. The high basal level of u-PA contributes to and may explain the higher angiogenic properties of hEMVEC (in vitro).

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