Takei A, Tashiro Y, Nakashima Y, Sueishi K
First Department of Pathology, Faculty of Medicine, Kyushu University 60, Fukuoka, Japan.
In Vitro Cell Dev Biol Anim. 1995 Jun;31(6):467-72. doi: 10.1007/BF02634260.
The effect of fibrin on angiogenesis in vitro was investigated using an experimental model of tube formation by bovine capillary endothelial cells (BCEs) in type I collagen gel. One milligram per milliliter of fibrin added into type I collagen gel significantly increased the length of the tubular structures formed by BCEs in the gel by about 180% compared with type I collagen only. The facilitating effect of fibrin on tube formation by BCEs was inhibited by either anti-basic fibroblast growth factor (bFGF) IgG (25 micrograms/ml) or anti-urokinase type plasminogen activator (uPA) IgG (10 micrograms/ml) added to the gel and culture medium, but not by anti-tissue type plasminogen activator (uPA) IgG (10 micrograms/ml) added to the gel and culture medium, but not by anti-tissue type plasminogen activator (10 micrograms/ml) or non-immune IgG. The Arg-Gly-Asp (RGD) containing peptides (100 micrograms/ml) added to the culture medium also suppressed tube formation by BCEs in fibrin-containing type I collagen gel, but not in type I collagen gel. These results suggest that the increased release of bFGF and uPA by BCEs therefore plays a role in the angiogenic effect of fibrin in vitro, and the angiogenic effect of fibrin is mediated by the RGD sequence in fibrin, probably via the function of integrin receptor of the BCEs.
利用牛毛细血管内皮细胞（BCEs）在I型胶原凝胶中形成管样结构的实验模型，研究了纤维蛋白对体外血管生成的影响。与仅含I型胶原的凝胶相比，向I型胶原凝胶中添加每毫升1毫克的纤维蛋白可使凝胶中BCEs形成的管状结构长度显著增加约180%。添加到凝胶和培养基中的抗碱性成纤维细胞生长因子（bFGF）IgG（25微克/毫升）或抗尿激酶型纤溶酶原激活剂（uPA）IgG（10微克/毫升）可抑制纤维蛋白对BCEs管样结构形成的促进作用，但添加到凝胶和培养基中的抗组织型纤溶酶原激活剂（10微克/毫升）或非免疫IgG则无此作用。添加到培养基中的含精氨酸 - 甘氨酸 - 天冬氨酸（RGD）的肽（100微克/毫升）也可抑制含纤维蛋白的I型胶原凝胶中BCEs的管样结构形成，但对I型胶原凝胶无此作用。这些结果表明，BCEs增加释放bFGF和uPA因此在纤维蛋白的体外血管生成作用中发挥作用，并且纤维蛋白的血管生成作用由纤维蛋白中的RGD序列介导，可能是通过BCEs的整合素受体功能实现的。
