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Myosin: a noncovalent stabilizer of fibrin in the process of clot dissolution


Kolev, K and Tenekedjiev, KI and Ajtai, K and Kovalsky, I and Gombas, J and Varadi, B and Machovich, R, Myosin: a noncovalent stabilizer of fibrin in the process of clot dissolution, Blood, 101, (11) pp. 4380-4386. ISSN 0006-4971 (2003) [Refereed Article]

Copyright Statement

Copyright 2003 The American Society of Hematology

DOI: doi:10.1182/blood-2002-10-3227


Myosin modulates the fibrinolytic process as a cofactor of the tissue plasminogen activator and as a substrate of plasmin. We report now that myosin is present in arterial thrombi and it forms reversible noncovalent complexes with fibrinogen and fibrin with equilibrium dissociation constants in the micromolar range (1.70 and 0.94 microM, respectively). Competition studies using a peptide inhibitor of fibrin polymerization (glycl-prolyl-arginyl-proline [GPRP]) indicate that myosin interacts with domains common in fibrinogen and fibrin and this interaction is independent of the GPRP-binding polymerization site in the fibrinogen molecule. An association rate constant of 1.81 x 10(2) M(-1) x s(-1) and a dissociation rate constant of 3.07 x 10(-4) s(-1) are determined for the fibrinogen-myosin interaction. Surface plasmon resonance studies indicate that fibrin serves as a matrix core for myosin aggregation. The fibrin clots equilibrated with myosin are stabilized against dissolution initiated by plasminogen and tissue-type plasminogen activator (tPA) or urokinase (at fibrin monomer-myosin molar ratio as high as 30) and by plasmin under static and flow conditions (at fibrin monomer-myosin molar ratio lower than 15). Myosin exerts similar effects on the tPA-induced dissolution of blood plasma clots. Covalent modification involving factor XIIIa does not contribute to this stabilizing effect; myosin is not covalently attached to the clot by the time of complete cross-linking of fibrin. Thus, our in vitro data suggest that myosin detected in arterial thrombi binds to the polymerized fibrin, in the bound form its tPA-cofactor properties are masked, and the myosin fibrin clot is relatively resistant to plasmin.

Item Details

Item Type:Refereed Article
Keywords:myosin kinetic modelling
Research Division:Information and Computing Sciences
Research Group:Artificial intelligence
Research Field:Modelling and simulation
Objective Division:Expanding Knowledge
Objective Group:Expanding knowledge
Objective Field:Expanding knowledge in the health sciences
UTAS Author:Tenekedjiev, KI (Professor Kiril Tenekedjiev)
ID Code:127972
Year Published:2003
Web of Science® Times Cited:14
Deposited By:Governance Office
Deposited On:2018-08-26
Last Modified:2018-10-09

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