Cellular procoagulant activity dictates clot structure and stability as a function of distance from the cell surface.
Cellular procoagulant activity dictates clot structure and stability as a function of distance from the cell surface.
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DOI：
10.1161/atvbaha.108.176008
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发表时间：
2008-12
期刊：
影响因子：
--
通讯作者：
Wolberg AS
中科院分区：
文献类型：
--
作者：
Campbell RA;Overmyer KA;Bagnell CR;Wolberg AS
凝血酶浓度调节纤维蛋白结构，纤维蛋白结构调节凝块稳定性；然而，先前尚未评估局部细胞表面驱动的原位凝血酶生成对纤维蛋白结构和稳定性的影响。将人成纤维细胞与因子 Xa、Va、凝血酶原和纤维蛋白原或血浆一起孵育。使用激光扫描共聚焦显微镜和透射电子显微镜检查纤维蛋白的形成、结构和裂解。细胞表面的原位凝血酶生成产生的凝块在细胞表面近端 10 μm 区域与远端（40 – 50 μm）区域具有明显更密集的纤维网络。这种形态不会因添加整合素阻断RGDS肽而改变，并且在添加外源凝血酶形成的凝块中并不明显，这表明空间形态主要由成纤维细胞表面上局部凝血酶的生成决定。与细胞表面近端相比，远端的纤维蛋白网络溶解得更快，这表明凝块的结构异质性影响了其纤溶稳定性。细胞表面的原位凝血酶生成调节凝块的三维结构和稳定性。体内血栓形成可能反映了局部细胞群支持凝血酶生成的能力，从而反映了纤维蛋白网络的三维结构和稳定性。
Thrombin concentration modulates fibrin structure and fibrin structure modulates clot stability; however, the impact of localized, cell surface-driven in situ thrombin generation on fibrin structure and stability has not previously been evaluated. Human fibroblasts were incubated with factors Xa, Va, prothrombin and fibrinogen, or plasma. Fibrin formation, structure, and lysis were examined using laser scanning confocal microscopy and transmission electron microscopy. in situ thrombin generation on the cell surface produced clots with a significantly denser fiber network in a 10-μm region proximal versus distal to (40 – 50 μm) the cell surface. This morphology was not altered by addition of integrin-blocking RGDS peptide and was not apparent in clots made by exogenous thrombin addition, suggesting that spatial morphology was dictated predominantly by localized thrombin generation on the fibroblast surface. The fibrin network lysed more rapidly distal versus proximal to the cell surface, suggesting that the clot’s structural heterogeneity affected its fibrinolytic stability. in situ thrombin generation on the cell surface modulates the three-dimensional structure and stability of the clot. Thrombus formation in vivo may reflect the ability of the local cell population to support thrombin generation and therefore, the three-dimensional structure and stability of the fibrin network.