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

Effects of Hyperhomocysteinemia on the Platelet-Driven Contraction of Blood Clots.
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高同型半胱氨酸血症对血小板驱动的血栓收缩的影响。

DOI:
10.3390/metabo11060354
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发表时间:
2021-06-01
期刊:
影响因子:
4.1
通讯作者:
Weisel JW
Weisel JW
中科院分区:
生物学3区
文献类型:
--
作者:
Litvinov RI;Peshkova AD;Le Minh G;Khaertdinov NN;Evtugina NG;Sitdikova GF;Weisel JW

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高同型半胱氨酸血症(HHcy)与血栓形成有关,但它们之间的机制联系尚不清楚。我们研究了同型半胱氨酸(Hcy)对体外凝块收缩的影响,并在大鼠模型的HHcy。孵育1分钟的血液与外源性同型半胱氨酸增强凝块收缩,而15分钟的孵育导致剂量依赖性抑制收缩。这些影响可能是由于直接同型半胱氨酸诱导的血小板活化,然后耗尽,所揭示的纤维蛋白原结合能力和P-选择素表达的增加,通过流式细胞术测定。在患有HHcy的大鼠的血液中,在适度升高的Hcy水平(10-50 μM)下,凝块收缩增强,而在较高的Hcy水平(>50 μM)下,凝块收缩的开始被延迟。高同型半胱氨酸与血小板增多、红细胞计数减少和低纤维蛋白原血症有关。这些数据表明,在HHcy中,血小板直接和间接地被激活,导致增强的凝块收缩,这是由凝块中纤维蛋白和红细胞的含量和弹性降低所促进的。过度的血小板活化可导致衰竭和收缩性受损,这使得凝块更大和更阻塞。总之,高同型半胱氨酸调节血凝块收缩,这可能包括一个低估的促或抗血栓形成机制。
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.
DOI: 10.1038/s41598-020-75234-y
发表时间: 2020-10-26
期刊: Scientific reports
影响因子: 4.6
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