Abstract

Endostatin is a potent angiogenic inhibitor that is derived from collagen XVIII by proteolytic cleavage. Localization of collagen XVIII has been reported in the basement membrane of blood vessels. To examine the involvement of collagen XVIII/endostatin during pregnancy, the distribution of collagen XVIII/endostatin protein in human umbilical vein was evaluated by immunohistochemistry. The expression of collagen XVIII/endostatin in cultured human umbilical vein endothelial cells (HUVEC) was also examined by immunocytochemistry and Northern blot analysis. To examine the release of endostatin in vivo and in vitro, concentrations of endostatin in umbilical venous blood and in HUVEC culture medium were determined using an enzyme-linked immunosorbent assay. Collagen XVIII/endostatin protein was localized to endothelial cells and their basement membrane in the umbilical vein. The expression of collagen XVIII mRNA and protein was detected in HUVEC. However, endostatin was not detected in umbilical venous blood or in HUVEC culture medium. The absence of endostatin release and the presence of its parental protein, collagen XVIII, suggest that the cleavage mechanisms of endostatin might be strongly inhibited under the physiological conditions present during pregnancy. It is therefore considered that vasculature in the feto-placental unit is highly angiogenic, even at the time of parturition.