Yoshida A, Anand-Apte B, Zetter B R
Department of Surgery Children's Hospital Boston, Massachusetts 02115, USA.
Growth Factors. 1996;13(1-2):57-64. doi: 10.3109/08977199609034566.
Neovascularization is a feature of a variety of pathological processes. We compared the characteristics of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) on migration and proliferation of human umbilical vein endothelium (HUVEC). Both VEGF and bFGF induced endothelial cell migration at similar concentrations (1/2 max. VEGF = approximately 1.0 ng/ml, bFGF = approximately 5.0 ng/ml). However, VEGF-stimulated migration was two-fold greater than bFGF at 1 and 10 ng/ml (p < 0.05). In contrast, bFGF induced proliferation four-fold more effectively than VEGF (1/2 max. 1 ng/ml and 1.4 ng/ml respectively). Checkerboard migration assays for bFGF showed a predominantly chemokinetic pattern, whereas VEGF was predominantly chemotactic. VEGF and bFGF were not synergistic in monolayer proliferation and migration assays. Three angiogenesis inhibitors, alpha-interferon, TNP-470, and platelet factor-4, inhibited VEGF and bFGF induced cell migration. These results indicate that VEGF and bFGF are chemoattractants that stimulate endothelial migration by different mechanisms and that both can be inhibited by known angiogenesis inhibitors.
新生血管形成是多种病理过程的一个特征。我们比较了血管内皮生长因子(VEGF)和碱性成纤维细胞生长因子(bFGF)对人脐静脉内皮细胞(HUVEC)迁移和增殖的影响。VEGF和bFGF在相似浓度下均可诱导内皮细胞迁移(VEGF的半数最大效应浓度约为1.0 ng/ml,bFGF约为5.0 ng/ml)。然而,在1 ng/ml和10 ng/ml时,VEGF刺激的迁移比bFGF高两倍(p < 0.05)。相反,bFGF诱导增殖的效果比VEGF高四倍(半数最大效应浓度分别为1 ng/ml和1.4 ng/ml)。bFGF的棋盘式迁移试验显示主要为化学动力学模式,而VEGF主要为趋化性。在单层增殖和迁移试验中,VEGF和bFGF没有协同作用。三种血管生成抑制剂,α-干扰素、TNP-470和血小板因子-4,可抑制VEGF和bFGF诱导的细胞迁移。这些结果表明,VEGF和bFGF是趋化因子,通过不同机制刺激内皮细胞迁移,并且两者均可被已知的血管生成抑制剂抑制。