Effects of Hyperhomocysteinemia on the Platelet-Driven Contraction of Blood Clots
| Autor: | Natalia G Evtugina, Giang Le Minh, Rustem I. Litvinov, John W. Weisel, N. N. Khaertdinov, Alina D. Peshkova, Guzel F. Sitdikova |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Hyperhomocysteinemia medicine.medical_specialty Contraction (grammar) Endocrinology Diabetes and Metabolism 030204 cardiovascular system & hematology contraction of blood clots Biochemistry Microbiology blood clotting Fibrin Article Contractility 03 medical and health sciences 0302 clinical medicine Internal medicine Antithrombotic medicine Platelet Platelet activation hyperhomocysteinemia Molecular Biology biology Chemistry homocysteine medicine.disease Thrombosis QR1-502 030104 developmental biology Endocrinology platelets biology.protein retraction of blood clots |
| Zdroj: | Metabolites Volume 11 Issue 6 Metabolites, Vol 11, Iss 354, p 354 (2021) |
| ISSN: | 2218-1989 |
| Popis: | Hyperhomocysteinemia (HHcy) is associated with thrombosis, but the mechanistic links between them are not understood. We studied effects of homocysteine (Hcy) on clot contraction in vitro and in a rat model of HHcy. Incubation of blood with exogenous Hcy for 1 min enhanced clot contraction, while 15-min incubation led to a dose-dependent suppression of contraction. These effects were likely due to direct Hcy-induced platelet activation followed by exhaustion, as revealed by an increase in fibrinogen-binding capacity and P-selectin expression determined by flow cytometry. In the blood of rats with HHcy, clot contraction was enhanced at moderately elevated Hcy levels (10–50 μM), while at higher Hcy levels (> 50 μM), the onset of clot contraction was delayed. HHcy was associated with thrombocytosis combined with a reduced erythrocyte count and hypofibrinogenemia. These data suggest that in HHcy, platelets get activated directly and indirectly, leading to enhanced clot contraction that is facilitated by the reduced content and resilience of fibrin and erythrocytes in the clot. The excessive platelet activation can lead to exhaustion and impaired contractility, which makes clots larger and more obstructive. In conclusion, HHcy modulates blood clot contraction, which may comprise an underappreciated pro- or antithrombotic mechanism. |
| Databáze: | OpenAIRE |
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