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Molecular mechanism of physiological fibrinolysis

Naturevolume 272pages549550 (1978) | Download Citation



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.

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  1. 1

    Alkjaersig, N., Fletcher, A. P. & Sherry, S. J. clin. Invest. 38, 1086–1095 (1959).

  2. 2

    Ambrus, C. M. & Markus, G. Am. J. Physiol. 199, 491–494 (1960).

  3. 3

    Chesterman, C. N., Allington, M. J. & Sharp, A. A. Nature new Biol. 238, 15–17 (1972).

  4. 4

    Thorsen, S. Biochim. biophys. Acta 393, 55–65 (1975).

  5. 5

    Wiman, B. & Wallén, P. Thromb. Res. 10, 213–222 (1977).

  6. 6

    Rákóczi, I., Wiman, B. & Collen, D. Biochim. biophys. Acta 540, 295–300 (1978).

  7. 7

    Iwamoto, M. Thromb. Diath. Haemorrh. 33, 573–585 (1975).

  8. 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. 9

    Wiman, B. & Wallén, P. Eur. J. Biochem. 50, 489–494 (1975).

  10. 10

    Thorsen, S., Glas-Greenwalt, P. & Astrup, T. Thromb. Diath. Haemorrh. 28, 65–74 (1972).

  11. 11

    Wallén, P. in Thrombosis and Urokinase (eds Paoletti, R. & Sherry, S.) 91–102 (Academic, London, 1977).

  12. 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. 13

    Collen, D. Eur. J. Biochem. 69, 209–216 (1976).

  14. 14

    Moroi, M. & Aoki, N. J. biol. Chem. 251, 5956–5965 (1976).

  15. 15

    Müllertz, S. & Clemmensen, I. Biochem. J. 159, 545–553 (1976).

  16. 16

    Wiman, B. & Collen, D. Eur. J. Biochem. 78, 19–26 (1977).

  17. 17

    Moroi, M. & Aoki, N. Thromb Res. 10, 851–856 (1977).

  18. 18

    Christensen, U. & Clemmensen, I. Biochem. J. 163, 389–391 (1977).

  19. 19

    Wiman, B. & Collen, D. Eur. J. Biochem 84, 573–578 (1978).

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  1. Department of Medical Chemistry, Umeå University, Sweden

  2. Center for Thrombosis and Vascular Research, University of Leuven, Belgium



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