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Article

Effects of Hyperhomocysteinemia on the Platelet-Driven Contraction of Blood Clots

1
Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
2
Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia
*
Author to whom correspondence should be addressed.
Academic Editors: Amedeo Lonardo and Martin Maly
Metabolites 2021, 11(6), 354; https://doi.org/10.3390/metabo11060354
Received: 7 April 2021 / Revised: 21 May 2021 / Accepted: 30 May 2021 / Published: 1 June 2021
(This article belongs to the Special Issue Thrombosis and Metabolism)
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. View Full-Text
Keywords: homocysteine; hyperhomocysteinemia; platelets; blood clotting; contraction of blood clots; retraction of blood clots homocysteine; hyperhomocysteinemia; platelets; blood clotting; contraction of blood clots; retraction of blood clots
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MDPI and ACS Style

Litvinov, R.I.; Peshkova, A.D.; Le Minh, G.; Khaertdinov, N.N.; Evtugina, N.G.; Sitdikova, G.F.; Weisel, J.W. Effects of Hyperhomocysteinemia on the Platelet-Driven Contraction of Blood Clots. Metabolites 2021, 11, 354. https://doi.org/10.3390/metabo11060354

AMA Style

Litvinov RI, Peshkova AD, Le Minh G, Khaertdinov NN, Evtugina NG, Sitdikova GF, Weisel JW. Effects of Hyperhomocysteinemia on the Platelet-Driven Contraction of Blood Clots. Metabolites. 2021; 11(6):354. https://doi.org/10.3390/metabo11060354

Chicago/Turabian Style

Litvinov, Rustem I., Alina D. Peshkova, Giang Le Minh, Nail N. Khaertdinov, Natalia G. Evtugina, Guzel F. Sitdikova, and John W. Weisel. 2021. "Effects of Hyperhomocysteinemia on the Platelet-Driven Contraction of Blood Clots" Metabolites 11, no. 6: 354. https://doi.org/10.3390/metabo11060354

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