ESTROGEN PROMOTES ANGIOGENIC ACTIVITY IN HUMAN UMBILICAL VEIN ENDOTHELIAL-CELLS IN-VITRO AND IN A MURINE MODEL

Background Angiogenesis is a critical event in wound healing, tumor gr owth, and the inflammatory vasculitides. Since women have a higher inc idence of many vasculitic diseases, we examined the effects of female sex steroids, particularly estradiol, on human umbilical vein endothel ial cell (HUVEC) behavior in vitro and on angiogenesis in vivo. Method s and Results HUVECs were grown in estrogen-free medium before each as say. Exogenous 17 beta-estradiol (1 to 5 nmol/L) increased cell attach ment to laminin, types I and IV collagen, and fibronectin, as well as to tissue culture plastic. After a confluent monolayer of cells was '' wounded'' by scraping, estradiol-treated (10(-8) mol/L) cells migrated into the wound three times faster than untreated cells. Cell prolifer ation on plastic and on laminin increased threefold to fivefold, respe ctively, in the presence of estradiol. Estradiol also enhanced the abi lity of HUVECs to organize into tubular networks when plated on a reco nstituted basement membrane, Matrigel. Estradiol effects on both the ' 'wounding'' assay and tube formation were blocked by the specific estr ogen receptor antagonist ICI 182,780. Ovariectomy markedly decreased i n vivo vascularization of Matrigel plugs coinjected with basic fibrobl ast growth factor in mice. With estrogen replacement, angiogenesis was increased to the levels observed in nonovariectomized mice. Conclusio ns These studies demonstrate that, in vitro and in vivo, estradiol enh ances endothelial cell activities important in neovascularization and suggest a promoting influence of estrogens on angiogenesis.