Skip to main content

Advertisement

SpringerLink
Log in

Platelet-dependent stimulation of prostacyclin synthesis by platelet-derived growth factor

  • Letter
  • Published:

From Nature

View current issue Submit your manuscript

Abstract

Prostacyclin (PGI2), an unstable metabolite of arachidonic acid synthesized by vascular endothelial and smooth muscle cells, is a potent vasodilator and endogenous inhibitor of platelet aggregation1–10. Regulation of PGI2 synthesis by the vessel wall is not well understood11–16. We have investigated the possibility that a product released from platelet granules during degranulation might modify vessel wall PGI2 biosynthesis. We report here that a non-dialysable, platelet-dependent factor in serum dramatically stimulates PGI2 synthesis by cultured bovine aortic endothelium, aortic smooth muscle, and adrenal capillary endothelium. Platelet-derived growth factor (PDGF), a releasable peptide contained within platelet alpha granules17–20, stimulates PGI2 synthesis by the above cell types as much as 100-fold. The concentrations of PDGF required to produce these effects are below the level reported in normal human serum18. We postulate that in vivo released PDGF may increase vessel wall PGI2 production as part of a negative feedback mechanism controlling platelet aggregation.

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. Moncada, S., Gryglewski, R., Bunting, S. & Vane, J. R. Nature 263, 663–665 (1976).

    Article  ADS  CAS  Google Scholar 

  2. Bunting, S., Gryglewski, R., Moncada, S. & Vane, J. R. Prostaglandins 12, 897–913 (1976).

    Article  CAS  Google Scholar 

  3. Gryglewski, R., Bunting, S., Moncada, S., Flower, R. & Vane, J. R. Prostaglandins 12, 685–713 (1976).

    Article  CAS  Google Scholar 

  4. Johnson, R. A. et al. Prostaglandins 12, 915–928 (1976).

    Article  CAS  Google Scholar 

  5. Baenziger, N. C., Dillender, M. J. & Majerus, P. W. Biochem. biophys. Res. Commun. 78, 294–301 (1977).

    Article  CAS  Google Scholar 

  6. Weksler, B. B., Marcus, A. J. & Jaffe, E. A. Proc. natn. Acad. Sci. U.S.A. 74, 3922–3926 (1977).

    Article  ADS  CAS  Google Scholar 

  7. Marcus, A. J., Weksler, B. B. & Jaffe, E. A. J. biol. Chem. 253, 7138–7141 (1978).

    CAS  PubMed  Google Scholar 

  8. Ryan, J. W., Ryan, U. S., Habliston, D. & Martin, L. Trans. Ass. Am. Physns 91, 343–350 (1978).

    CAS  Google Scholar 

  9. MacIntyre, D. E., Pearson, J. D. & Gordon, J. L. Nature 271, 549–551 (1978).

    Article  ADS  CAS  Google Scholar 

  10. Moncada, S. & Vane, J. R. Fedn Proc. 38, 66–71 (1979).

    CAS  Google Scholar 

  11. Moncada, S. & Vane, J. R. Br. med. Bull. 34, 129–135 (1978).

    Article  CAS  Google Scholar 

  12. Marcus, A. J., Weksler, B. B. & Jaffe, E. A. J. biol. Chem. 253, 7138–7141 (1978).

    CAS  PubMed  Google Scholar 

  13. Marcus, A. J. Prog. Hemat. 11, 147–173 (1979).

    CAS  PubMed  Google Scholar 

  14. Needleman, P. et al. J. clin. Invest. 61, 839–849 (1978).

    Article  CAS  Google Scholar 

  15. Baenziger, N. L., Becherer, P. R. & Majerus, P. W. Cell 16, 967–974 (1979).

    Article  CAS  Google Scholar 

  16. Smith, J. B. et al. Circulation 58, 126 (1978).

    Article  Google Scholar 

  17. Antoniades, H. N., Scher, C. D. & Stiles, C. O. Proc. natn. Acad. Sci. U.S.A. 76, 1809–1813 (1979).

    Article  ADS  CAS  Google Scholar 

  18. Antoniades, H. N. & Scher, C. D. Proc. natn. Acad. Sci. U.S.A. 74, 1973–1977 (1977).

    Article  ADS  CAS  Google Scholar 

  19. Kaplan, D. R., Chao, F. C., Stiles, C. D., Antoniades, H. N. & Scher, C. D. Blood 53, 1043–1052 (1979).

    CAS  PubMed  Google Scholar 

  20. Ross, R., Glomset, J., Kariya, B. & Harker, L. Proc. natn. Acad. Sci. U.S.A. 71, 1207 (1974).

    Article  ADS  CAS  Google Scholar 

  21. Gimbrone, M. A. Prog. Hemostasis & Thromb. 3, 1–28 (1976).

    Google Scholar 

  22. Jaffe, E. A., Hayer, L. W. & Wachman, R. L. J. clin. Invest. 52, 2757–2764 (1973).

    Article  CAS  Google Scholar 

  23. Booyse, F. M., Sedlak, B. J. & Rafelson, M. E. Jr Thromb. Diath. haemorrh. 34, 825–839 (1975).

    Article  CAS  Google Scholar 

  24. Jaffe, E. A., Nachman, R. C., Becker, C. G. & Minsk, C. R. J. clin. Invest. 52, 2745–2756 (1973).

    Article  CAS  Google Scholar 

  25. Gimbrone, M. A., Cotran, R. S. & Folkman, J. J. Cell Biol. 60, 673–684 (1974).

    Article  CAS  Google Scholar 

  26. Schwartz, S. M. In Vitro 14, 966–980 (1978).

    Article  CAS  Google Scholar 

  27. Ross, R. J. Cell Biol. 50, 172–186 (1971).

    Article  CAS  Google Scholar 

  28. Folkman, J., Haudenschild, C. & Zetter, B. Proc. natn. Acad. Sci. U.S.A. 76, 5217–5221 (1979).

    Article  ADS  CAS  Google Scholar 

  29. Maurer, P., Moskowitz, M., Levine, L. & Melamed, E. Prostaglandins Med. 4, 153–161 (1980).

    Article  CAS  Google Scholar 

  30. Hong, S. & Levine, L. J. biol. Chem. 251, 5814–5816 (1976).

    CAS  PubMed  Google Scholar 

  31. Weksler, B. B., Ley, C. & Jaffe, E. J. clin. Invest. 62, 923–930 (1978).

    Article  CAS  Google Scholar 

  32. Gryglewski, R., Korbut, R. & Splawinski, J. Haemostasis 8, 294–299 (1979).

    CAS  PubMed  Google Scholar 

  33. Lowry, O. H., Roseborough, N. J., Farr, A. L. & Randall, R. J. J. biol. Chem. 193, 265–275 (1951).

    CAS  Google Scholar 

  34. Shier, W. T. Proc. natn. Acad. Sci. U.S.A. 77, 137–141 (1980).

    Article  ADS  CAS  Google Scholar 

  35. Levine, L. & Moskowitz, M. A. Proc. natn. Acad. Sci. U.S.A. 76, 6632–6636 (1979).

    Article  ADS  CAS  Google Scholar 

  36. Levine, L. & Alam, I. Prostaglandins Med. 3, 295–304 (1979).

    Article  CAS  Google Scholar 

  37. Alam, I., Ohuchi, K. & Levine, L. Analyt. Biochem. 93, 339–345 (1979).

    Article  CAS  Google Scholar 

  38. Reinhard, J. F., Moskowitz, M. A., Sved, A. F. & Fernstrom, J. D. Life Sci. (in the press).

  39. Tukey, J. W. Biometrics 5, 99–114 (1949).

    Article  MathSciNet  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratory of Neural and Endocrine Regulation, Department of Nutrition and Food Science, Massachusetts Institute of Technology, Cambridge, Massachusetts, 02139

    Shaun R. Coughlin & Michael A. Moskowitz

  2. Section of Neurology, Department of Medicine, Peter Bent Brigham Hospital, Harvard Medical School, Boston, Massachusetts, 02115

    Michael A. Moskowitz

  3. Department of Surgery, Children's Hospital Medical Center, Harvard Medical School, Boston, Massachusetts, 02115

    Bruce R. Zetter

  4. Center for Blood Research, Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, 02115

    Harry N. Antoniades

  5. Department of Biochemistry, Brandeis University, Waltham, Massachusetts, 02154

    Lawrence Levine

Authors
  1. Shaun R. Coughlin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michael A. Moskowitz
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bruce R. Zetter
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Harry N. Antoniades
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Lawrence Levine
    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

Coughlin, S., Moskowitz, M., Zetter, B. et al. Platelet-dependent stimulation of prostacyclin synthesis by platelet-derived growth factor. Nature 288, 600–602 (1980). https://doi.org/10.1038/288600a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/288600a0

  • Springer Nature Limited

This article is cited by

Search

Navigation