Molecular mechanism of physiological fibrinolysis (original) (raw)
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- Published: 06 April 1978
Nature volume 272, pages 549–550 (1978)Cite this article
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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.
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Authors and Affiliations
- Department of Medical Chemistry, Umeå University, Sweden
BJÖRN WIMAN & DÉSIRÉ COLLEN - Center for Thrombosis and Vascular Research, University of Leuven, Belgium
BJÖRN WIMAN & DÉSIRÉ COLLEN
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- BJÖRN WIMAN
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WIMAN, B., COLLEN, D. Molecular mechanism of physiological fibrinolysis.Nature 272, 549–550 (1978). https://doi.org/10.1038/272549a0
- Received: 29 December 1977
- Accepted: 10 February 1978
- Issue Date: 06 April 1978
- DOI: https://doi.org/10.1038/272549a0