Molecular mechanism of physiological fibrinolysis (original) (raw)

Nature volume 272, pages 549–550 (1978)Cite this article

Abstract

THE proteolytic enzyme system in blood that is predominantly responsible for removal of fibrin deposits, is called the fibrinolytic system. This system consists of three main components: the proenzyme plasminogen, which can be activated by limited proteolysis to the proteolytic enzyme plasmin; plasminogen activators, the most important of which probably originates in the endothelial cells; and inhibitors, which can rapidly neutralise plasmin or interfere with the activation of plasminogen. The proteolytic enzyme plasmin has a broad specificity, which is not very different from that of trypsin. However, in vivo the main target of plasmin is fibrin. Three hypotheses have been put forward to explain this specificity. Alkjaersig _et al._1 have suggested that plasminogen is adsorbed to polymerising fibrin and converted to active enzyme by activators which diffuse into the thrombus. Plasmin would then exert its action in an environment relatively free of inhibitors. Ambrus and Markus2 have proposed that plasmin–inhibitor complexes formed in the circulation dissociate in the presence of fibrin, because plasmin has a greater affinity for fibrin than for its inhibitors. Chesterman _et al._3 suggested that the activators bind selectively to fibrin and transform plasminogen, which diffuses into the thrombus, to plasmin. During the past few years specific interactions at the molecular level have been demonstrated between the different components of the fibrinolytic system. These findings now enable us to formulate a molecular model for the regulation of fibrinolysis in vivo.

This is a preview of subscription content, access via your institution

Access options

Subscribe to this journal

Receive 51 print issues and online access

$199.00 per year

only $3.90 per issue

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Additional access options:

Similar content being viewed by others

References

  1. Alkjaersig, N., Fletcher, A. P. & Sherry, S. J. clin. Invest. 38, 1086–1095 (1959).
    Article CAS Google Scholar
  2. Ambrus, C. M. & Markus, G. Am. J. Physiol. 199, 491–494 (1960).
    CAS PubMed Google Scholar
  3. Chesterman, C. N., Allington, M. J. & Sharp, A. A. Nature new Biol. 238, 15–17 (1972).
    Article CAS Google Scholar
  4. Thorsen, S. Biochim. biophys. Acta 393, 55–65 (1975).
    Article CAS Google Scholar
  5. Wiman, B. & Wallén, P. Thromb. Res. 10, 213–222 (1977).
    Article CAS Google Scholar
  6. Rákóczi, I., Wiman, B. & Collen, D. Biochim. biophys. Acta 540, 295–300 (1978).
    Article Google Scholar
  7. Iwamoto, M. Thromb. Diath. Haemorrh. 33, 573–585 (1975).
    Article CAS Google Scholar
  8. Sottrup-Jensen, L., Claeys, H., Zajdel, M., Petersen, T. E. & Magnusson, S. in Progress in Chemical Fibrinolysis and Thrombolysis (eds Davidson, J. F., Rowan, R. M., Samama, M. M. & Desnoyers, P. C.) (Raven, New York, in the press).
  9. Wiman, B. & Wallén, P. Eur. J. Biochem. 50, 489–494 (1975).
    Article CAS Google Scholar
  10. Thorsen, S., Glas-Greenwalt, P. & Astrup, T. Thromb. Diath. Haemorrh. 28, 65–74 (1972).
    Article CAS Google Scholar
  11. Wallén, P. in Thrombosis and Urokinase (eds Paoletti, R. & Sherry, S.) 91–102 (Academic, London, 1977).
    Google Scholar
  12. Pepper, D. S. & Allen, R. Presented at the 3rd Woudschoten Conference on Screening Methods for Detection of a Tendency to Thrombosis, Utrecht The Netherlands, 26–29 October (1977).
  13. Collen, D. Eur. J. Biochem. 69, 209–216 (1976).
    Article CAS Google Scholar
  14. Moroi, M. & Aoki, N. J. biol. Chem. 251, 5956–5965 (1976).
    CAS PubMed Google Scholar
  15. Müllertz, S. & Clemmensen, I. Biochem. J. 159, 545–553 (1976).
    Article Google Scholar
  16. Wiman, B. & Collen, D. Eur. J. Biochem. 78, 19–26 (1977).
    Article CAS Google Scholar
  17. Moroi, M. & Aoki, N. Thromb Res. 10, 851–856 (1977).
    Article CAS Google Scholar
  18. Christensen, U. & Clemmensen, I. Biochem. J. 163, 389–391 (1977).
    Article CAS Google Scholar
  19. Wiman, B. & Collen, D. Eur. J. Biochem 84, 573–578 (1978).
    Article CAS Google Scholar

Download references

Author information

Authors and Affiliations

  1. Department of Medical Chemistry, Umeå University, Sweden
    BJÖRN WIMAN & DÉSIRÉ COLLEN
  2. Center for Thrombosis and Vascular Research, University of Leuven, Belgium
    BJÖRN WIMAN & DÉSIRÉ COLLEN

Authors

  1. BJÖRN WIMAN
    You can also search for this author inPubMed Google Scholar
  2. DÉSIRÉ COLLEN
    You can also search for this author inPubMed Google Scholar

Rights and permissions

About this article

Cite this article

WIMAN, B., COLLEN, D. Molecular mechanism of physiological fibrinolysis.Nature 272, 549–550 (1978). https://doi.org/10.1038/272549a0

Download citation

This article is cited by