The myeloperoxidase product, hypochlorous acid, reduces thrombus formation under flow and attenuates clot retraction and fibrinolysis in human blood
| Autor: | Ewa Chabielska, M. M. Tomasiak-Lozowska, Agata Golaszewska, Tomasz Rusak, Marta Iwanicka, Agnieszka Leszczynska, Natalia Marcinczyk, Tomasz Misztal |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Blood Platelets
0301 basic medicine Hypochlorous acid Plasmin medicine.medical_treatment Clot Retraction Clot retraction Fibrinogen Biochemistry Fibrin 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Physiology (medical) Fibrinolysis medicine Humans Thrombus Blood Coagulation Peroxidase Inflammation Hemostasis Factor XIII biology Chemistry Thrombin Thrombosis medicine.disease Hypochlorous Acid 030104 developmental biology Coagulation biology.protein Biophysics 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Free Radical Biology and Medicine. 141:426-437 |
| ISSN: | 0891-5849 |
| DOI: | 10.1016/j.freeradbiomed.2019.07.003 |
| Popis: | Hypochlorite (HOCl), a strong oxidant and antimicrobial agent, has been proposed to be associated with hemostatic abnormalities during inflammatory response. However, its complex impact on hemostasis is not completely understood. In this report we studied the effect of clinically relevant (micromolar) HOCl concentrations on thrombus formation under flow, kinetics of platelet-fibrin clot formation, its architecture, retraction, and lysis. We found that HOCl (up to 500 µM) did not affect kinetics of coagulation measured in whole blood. HOCl (500-1000 µM) markedly diminished thrombus formation under flow. Clot retraction rate was reduced by HOCl dose-dependently (50-500 µM). HOCl (125-500 µM) inhibited fibrinolysis in whole blood and in platelet-depleted plasma, dose-dependently. Activity of plasmin was reduced by HOCl at concentrations started from 500 µM. HOCl (up to 500 µM) did not reduce plasminogen binding to fibrin under flow. HOCl (125-500 µM) modulated architecture of fibrin- and platelet-fibrin clots towards structures made of thin and densely packed fibers. Exposure of pure fibrinogen to HOCl (10-1000 µM) resulted in formation of dityrosine and was associated with altered fibrin structure derived from such modified fibrinogen. HOCl-altered fibrin net structure was not related with modulation of platelet procoagulant response, thrombin generation, and factor XIII activity. We conclude that, in human blood, clinically relevant HOCl concentrations may inhibit thrombus formation under flow, clot retraction and fibrinolysis. Fibrinolysis and clot retraction seem to be the most sensitive to HOCl-evoked inhibition. HOCl-modified fibrinogen and altered clot structure associated with it are likely to be primary sources of attenuated fibrinolysis. |
| Databáze: | OpenAIRE |
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