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Recombinant fibroblast growth factor-1 promotes intimal hyperplasia and angiogenesis in arteries in vivo

Nature volume 362, pages 844846 (29 April 1993) | Download Citation

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Abstract

THE prototype members of the heparin-binding fibroblast growth factor (FGF) family1–6, 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 β-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.

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Affiliations

  1. Departments of Internal Medicine and Biological Chemistry, Howard Hughes Medical Institute, University of Michigan Medical Center, Ann Arbor, Michigan 48109-0650, USA

    • Elizabeth G. Nabel
    • , Zhi-yong Yang
    • , Gregory Plautz
    •  & Gary J. Nabel
  2. Department of Molecular Biology, American Red Cross, Rockville, Maryland 20855, USA

    • Reza Forough
    • , Xi Zhan
    •  & Thomas Maciag
  3. Department of Experimental Pathology Holland Laboratory, American Red Cross, Rockville, Maryland 20855, USA

    • Christian C. Haudenschild

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https://doi.org/10.1038/362844a0

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