Nabel E G, Yang Z Y, Plautz G, Forough R, Zhan X, Haudenschild C C, Maciag T, Nabel G J
Department of Internal Medicine, Howard Hughes Medical Institute, University of Michigan Medical Center, Ann Arbor 48109-0650.
Nature. 1993 Apr 29;362(6423):844-6. doi: 10.1038/362844a0.
The prototype members of the heparin-binding fibroblast growth factor (FGF) family, acidic FGF (FGF-1) and basic FGF (FGF-2), are among the growth factors that act directly on vascular cells to induce endothelial cell growth and angiogenesis. In vivo, the role of the FGF prototypes in vascular pathology has been difficult to determine. We report here the introduction, by direct gene transfer into porcine arteries, of a eukaryotic expression vector encoding a secreted form of FGF-1. This somatic transgenic model defines gene function in the arterial wall in vivo. FGF-1 expression induced intimal thickening in porcine arteries 21 days after gene transfer, in contrast to control arteries transduced with an Escherichia coli beta-galactosidase gene. Where there was substantial intimal hyperplasia, neocapillary formation was detected in the expanded intima. These findings suggest that FGF-1 induces intimal hyperplasia in the arterial wall in vivo and, through its ability to stimulate angiogenesis in the neointima, FGF-1 could stimulate neovascularization of atherosclerotic plaques. Potentially, gene transfer of FGF-1 could also be used as a genetic intervention to improve blood flow to ischaemic tissues in selected clinical settings.
肝素结合成纤维细胞生长因子（FGF）家族的原型成员，即酸性FGF（FGF-1）和碱性FGF（FGF-2），是直接作用于血管细胞以诱导内皮细胞生长和血管生成的生长因子之一。在体内，FGF原型在血管病理学中的作用一直难以确定。我们在此报告通过将编码分泌形式FGF-1的真核表达载体直接基因转移到猪动脉中。这种体细胞转基因模型在体内定义了动脉壁中的基因功能。与用大肠杆菌β-半乳糖苷酶基因转导的对照动脉相比，FGF-1表达在基因转移后21天诱导猪动脉内膜增厚。在有大量内膜增生的地方，在扩张的内膜中检测到新毛细血管形成。这些发现表明，FGF-1在体内诱导动脉壁内膜增生，并且通过其刺激新生内膜血管生成的能力，FGF-1可以刺激动脉粥样硬化斑块的新生血管形成。潜在地，FGF-1的基因转移也可以用作一种基因干预手段，以改善特定临床环境中缺血组织的血流。
