Effects of Hyperhomocysteinemia on the Platelet-Driven Contraction of Blood Clots
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...
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2021-06-01
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| Series: | Metabolites |
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| Online Access: | https://www.mdpi.com/2218-1989/11/6/354 |
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| author | Rustem I. Litvinov Alina D. Peshkova Giang Le Minh Nail N. Khaertdinov Natalia G. Evtugina Guzel F. Sitdikova John W. Weisel |
| author_facet | Rustem I. Litvinov Alina D. Peshkova Giang Le Minh Nail N. Khaertdinov Natalia G. Evtugina Guzel F. Sitdikova John W. Weisel |
| author_sort | Rustem I. Litvinov |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T10:48:27Z |
| format | Article |
| id | doaj.art-1449fdd803f443fea97061930334b8a3 |
| institution | Directory Open Access Journal |
| issn | 2218-1989 |
| language | English |
| last_indexed | 2024-03-10T10:48:27Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Metabolites |
| spelling | doaj.art-1449fdd803f443fea97061930334b8a32023-11-21T22:23:10ZengMDPI AGMetabolites2218-19892021-06-0111635410.3390/metabo11060354Effects of Hyperhomocysteinemia on the Platelet-Driven Contraction of Blood ClotsRustem I. Litvinov0Alina D. Peshkova1Giang Le Minh2Nail N. Khaertdinov3Natalia G. Evtugina4Guzel F. Sitdikova5John W. Weisel6Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USAInstitute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, RussiaInstitute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, RussiaInstitute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, RussiaInstitute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, RussiaInstitute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, RussiaDepartment of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USAHyperhomocysteinemia (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.https://www.mdpi.com/2218-1989/11/6/354homocysteinehyperhomocysteinemiaplateletsblood clottingcontraction of blood clotsretraction of blood clots |
| spellingShingle | Rustem I. Litvinov Alina D. Peshkova Giang Le Minh Nail N. Khaertdinov Natalia G. Evtugina Guzel F. Sitdikova John W. Weisel Effects of Hyperhomocysteinemia on the Platelet-Driven Contraction of Blood Clots Metabolites homocysteine hyperhomocysteinemia platelets blood clotting contraction of blood clots retraction of blood clots |
| title | Effects of Hyperhomocysteinemia on the Platelet-Driven Contraction of Blood Clots |
| title_full | Effects of Hyperhomocysteinemia on the Platelet-Driven Contraction of Blood Clots |
| title_fullStr | Effects of Hyperhomocysteinemia on the Platelet-Driven Contraction of Blood Clots |
| title_full_unstemmed | Effects of Hyperhomocysteinemia on the Platelet-Driven Contraction of Blood Clots |
| title_short | Effects of Hyperhomocysteinemia on the Platelet-Driven Contraction of Blood Clots |
| title_sort | effects of hyperhomocysteinemia on the platelet driven contraction of blood clots |
| topic | homocysteine hyperhomocysteinemia platelets blood clotting contraction of blood clots retraction of blood clots |
| url | https://www.mdpi.com/2218-1989/11/6/354 |
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