Inhibition of plasmin activity by sulfated polyvinylalcohol-acrylate copolymers

Gábor Vörös, Krasimir Kolev, Katalin Csomor, Raymund Machovich

Research output: Contribution to journalArticle

9 Citations (Scopus)


The effect of four sulfated polyvinylalcohol-acrylate copolymers and heparin on plasminogen activation and on plasmin activity is studied. The molecules differing in charge (proportion of negatively charged units 40.5%-73.5% of the total) and in size (5600 Da-8800 Da) accelerate plasminogen activation by 2- up to 4-fold at a 7-fold molar excess of the polyvinylacrylates over plasminogen. They, however, exert a concentration and charge-dependent effect on plasmin: both the amidolytic (half-maximal effect at a 1.33-3.66 molar excess of the polyvinylacrylates) and fibrinolytic (half-maximal effect at 1.23-1.72 molar excess of the polyvinylacrylates) activities of plasmin are inhibited. In contrast, heparin (a similarly carboxylated and sulfated polymer) and polyvinylacrylates with a low number of sulfate groups (30% sulfated monomers) at concentrations up to 2.2 μM do not affect plasminogen activation and plasmin activity in a milieu of physiological ionic strength. Experiments with plasmin derivatives lacking N-terminal peptides of different length (des-kringle1-4 and des-kringle1-5 plasmin) show identical changes in the protease activities, precluding involvement of the kringle-domain in the interaction with the polyvinylacrylates. Fluorescence studies evidence the charge-dependent binding of the polyvinylacrylates to plasmin, but not to plasminogen. Thus, through non-covalent interaction with the protease-domain of plasmin the polyvinylacrylates inhibit fibrinolysis. Since these sulfated copolymers inhibit both thrombin [4] and plasmin activity, they may be a useful therapeutic tool in situations when both the blood coagulation and the fibrinolytic system are activated (such as intravascular coagulation and fibrinolysis, ICF). Copyright (C) 2000 Elsevier Science Ltd.

Original languageEnglish
Pages (from-to)353-361
Number of pages9
JournalThrombosis research
Issue number4
Publication statusPublished - Nov 15 2000


  • Fibrinolysis
  • Heparin
  • Plasmin
  • Plasminogen activation
  • Sulfated copolymers

ASJC Scopus subject areas

  • Hematology

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