Hu G F
Center for Biochemical and Biophysical Sciences and Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA.
J Cell Biochem. 1998 Jun 1;69(3):326-35. doi: 10.1002/(sici)1097-4644(19980601)69:3<326::aid-jcb10>3.0.co;2-a.
Copper ions stimulate proliferation of human umbilical artery and vein endothelial cells but not human dermal fibroblasts or arterial smooth muscle cells. Incubation of human umbilical vein endothelial cells for 48 h with 500 microM CuSO4 in a serum-free medium in the absence of exogenous growth factors results in a twofold increase in cell number, similar to the cell number increase induced by 20 ng/ml of basic fibroblast growth factor under the same conditions. Copper-induced proliferation of endothelial cells is not inhibited by 10% fetal bovine serum or by the presence of antibodies against a variety of angiogenic, growth, and chemotactic factors including angiogenin, fibroblast growth factors, epidermal growth factor, platelet-derived growth factor, tumor necrosis factor-alpha, transforming growth factor-beta, macrophage/monocyte chemotactic and activating factor, and macrophage inflammatory protein-1alpha. Moreover, despite the previous observations that copper increased total specific binding of 125I-angiogenin to endothelial cells, binding to the 170 kDa receptor is not changed; hence, the mitogenic activity of angiogenin is not altered by copper. Copper-induced proliferation, along with early reports that copper induces migration of endothelial cells, may suggest a possible mechanism for the involvement of copper in the process of angiogenesis.
铜离子可刺激人脐动脉和静脉内皮细胞的增殖，但对人真皮成纤维细胞或动脉平滑肌细胞无此作用。在无外源性生长因子的无血清培养基中，将人脐静脉内皮细胞与500微摩尔硫酸铜孵育48小时，细胞数量会增加两倍，这与在相同条件下20纳克/毫升碱性成纤维细胞生长因子诱导的细胞数量增加相似。铜诱导的内皮细胞增殖不受10%胎牛血清的抑制，也不受针对多种血管生成、生长和趋化因子（包括血管生成素、成纤维细胞生长因子、表皮生长因子、血小板衍生生长因子、肿瘤坏死因子-α、转化生长因子-β、巨噬细胞/单核细胞趋化和激活因子以及巨噬细胞炎性蛋白-1α）的抗体存在的影响。此外，尽管先前观察到铜增加了125I-血管生成素与内皮细胞的总特异性结合，但与170 kDa受体的结合并未改变；因此，血管生成素的促有丝分裂活性不会因铜而改变。铜诱导的增殖以及早期关于铜诱导内皮细胞迁移的报道，可能提示了铜参与血管生成过程的一种可能机制。
