POTENT SYNERGISM BETWEEN VASCULAR ENDOTHELIAL GROWTH-FACTOR AND BASIC FIBROBLAST GROWTH-FACTOR IN THE INDUCTION OF ANGIOGENESIS INVITRO
POTENT SYNERGISM BETWEEN VASCULAR ENDOTHELIAL GROWTH-FACTOR AND BASIC FIBROBLAST GROWTH-FACTOR IN THE INDUCTION OF ANGIOGENESIS INVITRO
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DOI：
10.1016/0006-291x(92)92277-5
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发表时间：
1992-12-15
影响因子：
3.1
通讯作者：
MONTESANO, R
中科院分区：
文献类型：
--
作者：
PEPPER, MS;FERRARA, N;MONTESANO, R
血管内皮生长因子（Vascular endothelial growth factor， VEGF），又称血管通透性因子或促血管因子，是最近发现的一种内皮特异性有丝分裂原，在体内具有血管生成作用。我们在体外证明了VEGF的血管生成作用：将VEGF添加到生长在三维胶原凝胶表面的微血管内皮细胞中，诱导细胞侵入底层基质，形成毛细血管样小管，在约2.2nM （100ng/ml）时效果最佳。与等摩尔浓度（0.5nM）的碱性成纤维细胞生长因子（bFGF）相比，VEGF的效力约为前者的一半。最显著的效果是与bFGF联合使用：当同时添加VEGF和bFGF时，bFGF诱导的体外血管生成反应远远大于添加，并且比单独使用任何一种细胞因子的反应都要快。这些结果表明，与bFGF一样，VEGF通过对内皮细胞的直接作用诱导血管生成反应，并且通过协同作用，这两种细胞因子在体外诱导血管生成方面具有强大的协同作用。我们认为VEGF和bFGF之间的协同作用在体内血管生成的控制中起重要作用。
Vascular endothelial growth factor (VEGF), also known as vascular permeability factor or vasculotropin, is a recently characterized endothelial-specific mitogen which is angiogenic in vivo. Here we demonstrate that VEGF is angiogenic in vitro: when added to microvascular endothelial cells grown on the surface of three-dimensional collagen gels, VEGF induces the cells to invade the underlying matrix and to form capillary-like tubules, with an optimal effect at approximately 2.2nM (100ng/ml). When compared to basic fibroblast growth factor (bFGF) at equimolar (0.5nM) concentrations, VEGF was about half as potent. The most striking effect was seen in combination with bFGF: when added simultaneously, VEGF and bFGF indubFGF induced an in vitro angiogenic response which was far greater than additive, and which occurred with greater rapidity than the response to either cytokine alone. These results demonstrate that like bFGF, VEGF induces an angiogenic response via a direct effect on endothelial cells, and that by acting in concert, these two cytokines have a potent synergistic effect on the induction of angiogenesis in vitro. We suggest that the synergism between VEGF and bFGF plays an important role in the control of angiogenesis in vivo.