Clot Contraction Drives the Translocation of Procoagulant Platelets to Thrombus Surface
Clot Contraction Drives the Translocation of Procoagulant Platelets to Thrombus Surface
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DOI：
10.1161/atvbaha.118.311390
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发表时间：
2019-01-01
影响因子：
8.7
通讯作者：
Panteleev, Mikhail A.
中科院分区：
文献类型：
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作者：
Nechipurenko, Dmitry Y.;Receveur, Nicolas;Panteleev, Mikhail A.
血小板-在血管损伤部位活化后，血小板分化成2个亚群，表现出促聚集或促凝血表型。尽管促血小板聚集的功能作用已经得到了很好的证实，但促凝血血小板的生理意义、其形成的动力学以及在血栓中的空间分布仍然是难以捉摸的。方法和结果利用透射电子显微镜和荧光显微镜观察了氯化铁诱导的小鼠颈动脉损伤或腹主动脉机械损伤后体内形成的动脉血栓，我们证明了促凝血血小板位于形成的血栓的外围。体外血栓形成过程中的实时细胞跟踪显示，促凝血血小板来源于血栓内的不同位置，随后向其外周移位。这种促凝血小板的重新分布之后是血栓表面纤维蛋白的产生。使用计算机模拟模型，我们表明，促凝血血小板的向外易位可以由形成血栓的收缩驱动，该收缩机械地将这些非聚集性细胞驱逐到血栓外周。与所提出的机制一致，促凝血血小板未能移位，并保留在来自非肌肉肌球蛋白（MYH 9）缺陷小鼠的血液中离体形成的血栓内。环状分布的促凝血血小板和纤维蛋白周围的血栓观察与血液的人和野生型小鼠是不存在于血栓的MYH 9基因敲除小鼠，确认血栓收缩在这一现象的主要作用。结论-收缩动脉血栓是负责的机械挤压促凝血血小板到其外周，导致血栓外部的异质结构。
Objective-After activation at the site of vascular injury, platelets differentiate into 2 subpopulations, exhibiting either proaggregatory or procoagulant phenotype. Although the functional role of proaggregatory platelets is well established, the physiological significance of procoagulant platelets, the dynamics of their formation, and spatial distribution in thrombus remain elusive.Approach and Results-Using transmission electron microscopy and fluorescence microscopy of arterial thrombi formed in vivo after ferric chloride-induced injury of carotid artery or mechanical injury of abdominal aorta in mice, we demonstrate that procoagulant platelets are located at the periphery of the formed thrombi. Real-time cell tracking during thrombus formation ex vivo revealed that procoagulant platelets originate from different locations within the thrombus and subsequently translocate towards its periphery. Such redistribution of procoagulant platelets was followed by generation of fibrin at thrombus surface. Using in silico model, we show that the outward translocation of procoagulant platelets can be driven by the contraction of the forming thrombi, which mechanically expels these nonaggregating cells to thrombus periphery. In line with the suggested mechanism, procoagulant platelets failed to translocate and remained inside the thrombi formed ex vivo in blood derived from nonmuscle myosin (MYH9)-deficient mice. Ring-like distribution of procoagulant platelets and fibrin around the thrombus observed with blood of humans and wild-type mice was not present in thrombi of MYH9-knockout mice, confirming a major role of thrombus contraction in this phenomenon.Conclusions-Contraction of arterial thrombus is responsible for the mechanical extrusion of procoagulant platelets to its periphery, leading to heterogeneous structure of thrombus exterior.