ESTROGEN PROMOTES ANGIOGENIC ACTIVITY IN HUMAN UMBILICAL VEIN ENDOTHELIAL-CELLS IN-VITRO AND IN A MURINE MODEL
ESTROGEN PROMOTES ANGIOGENIC ACTIVITY IN HUMAN UMBILICAL VEIN ENDOTHELIAL-CELLS IN-VITRO AND IN A MURINE MODEL
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DOI：
10.1161/01.cir.91.3.755
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发表时间：
1995-02-01
期刊：
影响因子：
37.8
通讯作者：
SCHNAPER, HW
中科院分区：
文献类型：
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作者：
MORALES, DE;MCGOWAN, KA;SCHNAPER, HW
背景血管生成是伤口愈合、肿瘤生长和炎性血管炎中的关键事件。由于女性许多血管炎疾病的发病率较高，因此我们研究了女性性类固醇（尤其是雌二醇）对人脐静脉内皮细胞 (HUVEC) 体外行为和体内血管生成的影响。 方法和结果 每次测定前，HUVEC 均在不含雌激素的培养基中生长。外源 17 β-雌二醇（1 至 5 nmol/L）可增加细胞与层粘连蛋白、I 型和 IV 型胶原、纤连蛋白以及组织培养塑料的附着。当汇合的单层细胞被刮擦“损伤”后，经过雌二醇处理（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。在雌二醇存在下，塑料和层粘连蛋白上的细胞增殖分别增加三至五倍。当铺在重构的基底膜基质胶上时，雌二醇还增强了 HUVEC 组织成管状网络的能力。雌二醇对“伤口”测定和管形成的影响均被特异性雌激素受体拮抗剂 ICI 182,780 阻断。卵巢切除术显着减少了小鼠体内与碱性成纤维细胞生长因子共注射的基质胶塞的血管化。通过补充雌激素，血管生成增加至在未切除卵巢的小鼠中观察到的水平。结论这些研究表明，在体外和体内，雌二醇可增强在新血管形成中重要的内皮细胞活性，并表明雌激素对血管生成具有促进作用。
Background 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.Methods and Results 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.Conclusions 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.