Morales D E, McGowan K A, Grant D S, Maheshwari S, Bhartiya D, Cid M C, Kleinman H K, Schnaper H W
Laboratory of Developmental Biology, National Institute of Dental Research, Bethesda, Md.
Circulation. 1995 Feb 1;91(3):755-63. doi: 10.1161/01.cir.91.3.755.
Angiogenesis is a critical event in wound healing, tumor growth, and the inflammatory vasculitides. Since women have a higher incidence of many vasculitic diseases, we examined the effects of female sex steroids, particularly estradiol, on human umbilical vein endothelial cell (HUVEC) behavior in vitro and on angiogenesis in vivo.
HUVECs were grown in estrogen-free medium before each assay. Exogenous 17 beta-estradiol (1 to 5 nmol/L) increased cell attachment 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 proliferation on plastic and on laminin increased threefold to fivefold, respectively, in the presence of estradiol. Estradiol also enhanced the ability of HUVECs to organize into tubular networks when plated on a reconstituted basement membrane, Matrigel. Estradiol effects on both the "wounding" assay and tube formation were blocked by the specific estrogen receptor antagonist ICI 182,780. Ovariectomy markedly decreased in vivo vascularization of Matrigel plugs coinjected with basic fibroblast growth factor in mice. With estrogen replacement, angiogenesis was increased to the levels observed in nonovariectomized mice.
These studies demonstrate that, in vitro and in vivo, estradiol enhances endothelial cell activities important in neovascularization and suggest a promoting influence of estrogens on angiogenesis.
血管生成是伤口愈合、肿瘤生长和炎症性血管炎中的关键事件。由于女性多种血管炎疾病的发病率较高，我们研究了女性性激素，尤其是雌二醇，对体外人脐静脉内皮细胞（HUVEC）行为及体内血管生成的影响。
每次检测前，将HUVEC在无雌激素的培养基中培养。外源性17β - 雌二醇（1至5 nmol/L）增加了细胞与层粘连蛋白、I型和IV型胶原以及纤连蛋白的附着，也增加了与组织培养塑料的附着。当汇合的单层细胞通过刮擦造成“伤口”后，用雌二醇处理（10⁻⁸ mol/L）的细胞迁移到伤口的速度比未处理的细胞快三倍。在有雌二醇存在的情况下，细胞在塑料和层粘连蛋白上的增殖分别增加了三到五倍。当接种在重组基底膜基质胶上时，雌二醇还增强了HUVEC组织形成管状网络的能力。雌二醇对“伤口”检测和管形成的作用均被特异性雌激素受体拮抗剂ICI 182,780阻断。卵巢切除显著降低了与碱性成纤维细胞生长因子共同注射到小鼠体内的基质胶栓的体内血管化程度。给予雌激素替代后，血管生成增加到未卵巢切除小鼠所观察到的水平。
这些研究表明，在体外和体内，雌二醇增强了在新血管形成中重要的内皮细胞活性，并提示雌激素对血管生成有促进作用。
