Murakami Masahiro, Simons Michael
Angiogenesis Research Center and Section of Cardiology, Department of Medicine, Dartmouth Medical School, Lebanon, New Hampshire 03756, USA.
Curr Opin Hematol. 2008 May;15(3):215-20. doi: 10.1097/MOH.0b013e3282f97d98.
Fibroblast growth factors are potent angiogenic inducers; however, their precise roles in angiogenesis have not been well understood. In this review, we will focus on specific roles played by fibroblast growth factors in neovascularization.
Although fibroblast growth factors promote a strong angiogenic response, it has been suggested that FGF-induced angiogenesis requires activation of the vascular endothelial growth factor system. Recent findings have endorsed the view of indirect contribution of fibroblast growth factor signaling to vascular development. A study using embryoid bodies demonstrated a nonimmediate role played by fibrobalst growth factor receptor 1 in vasculogenesis as vascular endothelial growth factor supplementation was sufficient to promote vascular development in Fgfr1-/- embryoid bodies. Moreover, another line of evidence indicated that myocardial fibroblast growth factor signaling is essential for mouse coronary development. The key role of fibroblast growth factor signaling in this process is Hedgehog activation, which induces vascular endothelial growth factor expression and formation of the coronary vasculature. In addition to vascular endothelial growth factor interaction, fibroblast growth factors can control neovascularization by influencing other growth factors and chemokines such as platelet-derived growth factor, hepatocyte growth factor and monocyte chemoattractant protein-1, contributing to development of mature vessels and collateral arteries.
Although fibroblast growth factors are potent angiogenic factors, they may indirectly control neovascularization in concert with other growth factors. Thus, the unique role played by fibroblast growth factors might be organization of various angiogenic pathways and coordination of cell-cell interactions in this process.
成纤维细胞生长因子是强大的血管生成诱导剂;然而,它们在血管生成中的精确作用尚未得到充分理解。在本综述中,我们将聚焦于成纤维细胞生长因子在新生血管形成中所起的特定作用。
尽管成纤维细胞生长因子可促进强烈的血管生成反应,但有研究表明,成纤维细胞生长因子诱导的血管生成需要血管内皮生长因子系统的激活。最新研究结果支持了成纤维细胞生长因子信号传导对血管发育起间接作用的观点。一项使用胚状体的研究表明,成纤维细胞生长因子受体1在血管生成中并非立即发挥作用,因为补充血管内皮生长因子足以促进Fgfr1-/-胚状体中的血管发育。此外,另一系列证据表明,心肌成纤维细胞生长因子信号传导对小鼠冠状动脉发育至关重要。成纤维细胞生长因子信号传导在此过程中的关键作用是激活刺猬信号通路,该通路可诱导血管内皮生长因子表达并形成冠状动脉血管系统。除了与血管内皮生长因子相互作用外,成纤维细胞生长因子还可通过影响其他生长因子和趋化因子(如血小板衍生生长因子、肝细胞生长因子和单核细胞趋化蛋白-1)来控制新生血管形成,从而促进成熟血管和侧支动脉的发育。
尽管成纤维细胞生长因子是强大的血管生成因子,但它们可能与其他生长因子协同间接控制新生血管形成。因此,成纤维细胞生长因子所起的独特作用可能是在此过程中组织各种血管生成途径并协调细胞间相互作用。