Peroxynitrite may affect fibrinolysis via the reduction of platelet-related fibrinolysis resistance and alteration of clot structure
| Autor: | Tomasz Rusak, Marian Tomasiak, Justyna Brańska-Januszewska, Tomasz Misztal, Halina Ostrowska |
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| Rok vydání: | 2015 |
| Předmět: |
inorganic chemicals
Adult Blood Platelets Male Adolescent medicine.medical_treatment Clot retraction Biochemistry chemistry.chemical_compound Young Adult Thrombin Physiology (medical) Peroxynitrous Acid Fibrinolysis medicine Humans Platelet Blood Coagulation Microscopy Confocal Phosphatidylserine Peroxynitrous acid chemistry Clotting time cardiovascular system Biophysics Female Peroxynitrite circulatory and respiratory physiology medicine.drug |
| Zdroj: | Free radical biologymedicine. 89 |
| ISSN: | 1873-4596 |
| Popis: | We tested the hypothesis that in vitro peroxynitrite (ONOO(-), a product of activated inflammatory cells) may affect fibrinolysis in human blood through the reduction of platelet-related fibrinolysis resistance. It was found that ONOO(-) (25-300 µM) accelerated lysis of platelet-fibrin clots (in PRP) dose-dependently, whereas fibrinolysis of platelet-free clots was slightly inhibited by ≥ 1000 µM stressor. Concentrations of ONOO(-) affecting the lysis of platelet-rich clots, inhibited clot retraction (CR) in a dose-dependent manner. Thromboelastometry (ROTEM) measurements performed in PRP showed that treatment with ONOO(-) (threshold conc. 100 µM) prolongs clotting time, and reduces alpha angle, and clot formation velocity parameters indicating for reduced thrombin formation rate. In PRP, ONOO(-) (threshold conc. 100 µM) reduced the collagen-evoked exposure of phosphatidylserine (PS) on platelets' plasma membrane, the shedding of platelet-derived microparticles (PMP), and inhibited platelet-dependent thrombin generation (measured in artificial system), dose-dependently. As judged by confocal microscopy, similar ONOO(-) concentrations altered the architecture of clots formed in collagen-treated PRP. Clots formed in the presence of ONOO(-) were less dense and were composed of thicker fibers, which make them more susceptible to lysis. In platelet-depleted plasma, ONOO(-) (up to milimolar concentration) did not alter clot structure. Blockage of PS exposed on platelets resulted in an alteration of clot architecture toward more prone to lysis. ONOO(-), at lysis-affecting concentrations, inhibited the collagen-evoked secretion of fibrinolytic inhibitors from platelets. We conclude that physiologically relevant ONOO(-) concentrations may accelerate the lysis of platelet-fibrin clots predominantly via downregulation of platelet-related mechanisms including: platelet secretion, clot retraction, platelet procoagulant response, and the alteration in clot architecture associated with it. |
| Databáze: | OpenAIRE |
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