Insight into the profibrinolytic activity of dermatan sulfate: effects on the activation of plasminogen mediated by tissue and urinary plasminogen activators

Thromb Res. 2007;120(5):745-52. doi: 10.1016/j.thromres.2006.12.014. Epub 2007 Jan 31.


Introduction: Dermatan sulfate (DS) is well-known for its anticoagulant activity through binding to heparin cofactor II to enhance antithrombin action. It has also been suggested that DS has a profibrinolytic effect, although the exact molecular mechanism is as yet unknown.

Materials and methods: An in vitro amidolytic method was used to study the effect of high and low molecular weight-DS on the activation of Glu and Lys-plasminogen by tissue and urinary plasminogen activators (t-PA and u-PA).

Results: Both high and low molecular weight-DS exhibited a stimulating effect on the activation of plasminogen by PAs. Interestingly, high molecular weight-DS stimulated Glu and Lys-plasminogen activation by t-PA and u-PA in a way and to an extent similar to that in which fibrin(ogen) degradation products (PDF) increased the t-PA assay. Meanwhile low molecular weight-DS had a lower effect. No DS had any effect on plasmin or u-PA amidolytic activity. The facilitation of the conversion of Glu-plasminogen to plasmin in the presence of DS was confirmed by SDS-PAGE; high molecular weight-DS effect was greater than low molecular weight-DS in accordance with the chromogenic assays. Moreover, the combination of PDF and high and low molecular weight-DS, respectively, did not further stimulate t-PA activation of either Glu or Lys-plasminogen suggesting that both substances may compete for the same binding sites.

Conclusions: Through in vitro assays we demonstrated that high and low molecular weight-DS enhance plasminogen activation by u-PA and t-PA, suggesting that the profibrinolytic activity of DS might be via potentiation of plasminogen conversion to plasmin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticoagulants / metabolism
  • Antithrombins / metabolism
  • Dermatan Sulfate / chemistry
  • Dermatan Sulfate / pharmacology*
  • Fibrinolysin / metabolism
  • Fibrinolysis / drug effects*
  • Glutamic Acid / chemistry
  • Humans
  • Hydrolysis
  • Models, Chemical
  • Molecular Weight
  • Peptide Fragments / chemistry
  • Plasminogen / chemistry
  • Plasminogen Activators / metabolism
  • Time Factors
  • Tissue Plasminogen Activator / metabolism
  • Urokinase-Type Plasminogen Activator / metabolism


  • Anticoagulants
  • Antithrombins
  • Peptide Fragments
  • lysyl-plasminogen
  • Dermatan Sulfate
  • Glutamic Acid
  • Plasminogen
  • Plasminogen Activators
  • Tissue Plasminogen Activator
  • Fibrinolysin
  • Urokinase-Type Plasminogen Activator