Skip to main content
SpringerLink
Log in

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

  • Letter
  • Published:

From Nature

View current issue Submit your manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Burgess, W. H. & Maciag, T. A. Rev, Biochem. 58, 575–606 (1989).

    Article  CAS  Google Scholar 

  2. Ausprunk, D. H. & Folkman, J. Microvasc. Res. 14, 53–65 (1977).

    Article  CAS  Google Scholar 

  3. Abraham, J. A. et al. Science 233, 545–548 (1986).

    Article  ADS  CAS  Google Scholar 

  4. Gospodarowicz, D., Chen, J., Lui, G. M., Baird, A. & Bohlent, P. Proc. natn. Acad. Sci. U.S.A. 81, 6963–6967 (1984).

    Article  ADS  CAS  Google Scholar 

  5. Thomas, K. A. et al. Proc. natn. Acad. Sci. U.S.A. 82, 6409–6413 (1985).

    Article  ADS  CAS  Google Scholar 

  6. Yanagisawa-Miwa, A. et al. Science 257, 1401–1403 (1992).

    Article  ADS  CAS  Google Scholar 

  7. Nabel, E. G., Plautz, G., Boyce, F. M., Stanley, J. C. & Nabel, G. J. Science 244, 1342–1344 (1989).

    Article  ADS  CAS  Google Scholar 

  8. Nabel, E. G., Plautz, G. & Nabel, G. J. Science 249, 1285–1288 (1990).

    Article  ADS  CAS  Google Scholar 

  9. Plautz, G., Nabel, E. G. & Nabel, G. J. Circulation 83, 578–583 (1991).

    Article  CAS  Google Scholar 

  10. Lim, C. S. et al. Circulation 83, 2007–2011 (1991).

    Article  CAS  Google Scholar 

  11. Chapman, G. D. et al. Circ. Res. 71, 27–33 (1992).

    Article  CAS  Google Scholar 

  12. Leclerc, G., Gal, D., Takeshita, S., Nikol, S., Weir, L. & Isner, J. M. J. clin. Invest. 90, 936–944 (1992).

    Article  CAS  Google Scholar 

  13. Forough, R. et al. J. biol. Chem. 268, 2960–2968 (1993).

    CAS  PubMed  Google Scholar 

  14. Martin-Zanca, D., Oskam, R., Mitra, G., Copeland, T. & Barbacid, M. Molec. cell. Biol. 9, 24–33 (1989).

    Article  CAS  Google Scholar 

  15. Nabel, E. G., Plautz, G. & Nabel, G. J. Proc. natn. Acad. Sci U.S.A. 89, 5157–5161 (1992).

    Article  ADS  CAS  Google Scholar 

  16. Nabel, E. G. et al. J. clin. Invest 91, 1822–1829 (1993).

    Article  CAS  Google Scholar 

  17. Gajdusek, C. M. & Carbon, S. J. Cell Physiol. 139, 570–579 (1989).

    Article  CAS  Google Scholar 

  18. McNeil, P. L., Muthukrishnan, L., Warder, E. & D'Amore, P. A. J. Cell Biol. 109, 811–822 (1989).

    Article  CAS  Google Scholar 

  19. Viodavsky, I., Folkman, J., Sullivan, R., Friedman, R. & Ishai-Michaeli, R. Proc. natn. Acad. Sci. U.S.A. 84, 2292–2296 (1987).

    Article  ADS  Google Scholar 

  20. Jackson, A. et al. Proc. natn. Acad. Sci. U.S.A. 99, 10691–10695 (1992).

    Article  Google Scholar 

  21. Lindner, V., Lappi, D. A., Baird, A., Majack, R. A. & Reidy, M. A. Circ. Res. 68, 106–113 (1991).

    Article  CAS  Google Scholar 

  22. Jawien, A., Bowen-Pope, D. F., Lindner, V., Schwartz, S. M. & Clowes, A. J. clin. Invest. 89, 507–511 (1992).

    Article  CAS  Google Scholar 

  23. Barger, A. C., Beeuwkes, R. III, Lainey, L. L. & Silverman, K. J. N. Engl. J. Med. 310, 175–177 (1984).

    Article  CAS  Google Scholar 

  24. Mosmann, T. J. immun. Meth. 65, 55–63 (1983).

    Article  CAS  Google Scholar 

  25. Ellis, S. A., Taylor, C. & McMichael, A. Hum. Immun. 5, 49–59 (1982).

    Article  CAS  Google Scholar 

  26. Clowes, A. W., Clowes, M. M. & Reidy, M. A. Lab Invest. 54, 295–303 (1986).

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and 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

Authors
  1. Elizabeth G. Nabel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zhi-yong Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gregory Plautz
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Reza Forough
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xi Zhan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Christian C. Haudenschild
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Thomas Maciag
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Gary J. Nabel
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nabel, E., Yang, Zy., Plautz, G. et al. Recombinant fibroblast growth factor-1 promotes intimal hyperplasia and angiogenesis in arteries in vivo. Nature 362, 844–846 (1993). https://doi.org/10.1038/362844a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

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

  • Springer Nature Limited

This article is cited by

Search

Navigation