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

K. Kolev, Kiril Tenekedjiev, Katalin Ajtai, I. Kovalszky, Judit Gombás, Balázs Váradi, R. Machovich

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

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 μM, 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 × 102 M-1. s-1 and a dissociation rate constant of 3.07 × 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.

Original languageEnglish
Pages (from-to)4380-4386
Number of pages7
JournalBlood
Volume101
Issue number11
DOIs
Publication statusPublished - Jun 1 2003

Fingerprint

Nonmuscle Myosin Type IIA
Myosins
Fibrin
Dissolution
arginyl-prolyl-proline
Fibrinogen
Fibrinolysin
Thrombosis
Plasminogen Activators
Tissue Plasminogen Activator
Polymerization
Rate constants
Factor XIIIa
Surface Plasmon Resonance
Plasminogen
Urokinase-Type Plasminogen Activator
Surface plasmon resonance

ASJC Scopus subject areas

  • Hematology

Cite this

Myosin : A noncovalent stabilizer of fibrin in the process of clot dissolution. / Kolev, K.; Tenekedjiev, Kiril; Ajtai, Katalin; Kovalszky, I.; Gombás, Judit; Váradi, Balázs; Machovich, R.

In: Blood, Vol. 101, No. 11, 01.06.2003, p. 4380-4386.

Research output: Contribution to journalArticle

Kolev, K. ; Tenekedjiev, Kiril ; Ajtai, Katalin ; Kovalszky, I. ; Gombás, Judit ; Váradi, Balázs ; Machovich, R. / Myosin : A noncovalent stabilizer of fibrin in the process of clot dissolution. In: Blood. 2003 ; Vol. 101, No. 11. pp. 4380-4386.
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