Contributions of extravascular and intravascular cells to fibrin network formation, structure, and stability
Contributions of extravascular and intravascular cells to fibrin network formation, structure, and stability
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DOI：
10.1182/blood-2009-06-228940
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发表时间：
2009-11-26
期刊：
影响因子：
20.3
通讯作者：
Wolberg, Alisa S.
中科院分区：
文献类型：
--
作者：
Campbell, Robert A.;Overmyer, Katherine A.;Wolberg, Alisa S.
纤维蛋白对于止血至关重要；然而，据推测，异常的纤维蛋白形成会增加血栓形成的风险。我们之前表明，细胞表面的原位凝血酶生成可调节纤维蛋白网络的三维结构和稳定性。目前，我们比较了血管外和血管内细胞支持纤维蛋白形成、结构和稳定性的能力。血管外细胞（成纤维细胞、平滑肌）支持形成抗纤维蛋白溶解的致密纤维蛋白网络，而未受刺激的血管内（内皮）细胞产生易于纤维蛋白溶解的粗糙网络。所有 3 种细胞类型均产生纤维蛋白结构梯度，与细胞表面远端相比，靠近细胞表面的网络更密集。尽管纤维蛋白结构取决于细胞促凝血活性，但它并不反映整合素和纤维蛋白之间的相互作用。这些发现与血小板的研究结果形成鲜明对比，血小板通过β3整合素和纤维蛋白之间的相互作用影响纤维蛋白结构。在内皮细胞上诱导血栓前活性的炎症细胞因子导致异常致密的纤维蛋白网络的产生，从而抵抗纤维蛋白溶解。阻断组织因子活性显着降低细胞因子刺激的内皮细胞产生的纤维蛋白网络的密度和稳定性。总之，这些发现表明纤维蛋白结构和稳定性反映了内源性细胞的促凝血表型，并表明异常的纤维蛋白结构是炎症和血栓形成之间的新联系。 （血。2009；114：4886-4896）
Fibrin is essential for hemostasis; however, abnormal fibrin formation is hypothesized to increase thrombotic risk. We previously showed that in situ thrombin generation on a cell's surface modulates the 3-dimensional structure and stability of the fibrin network. Currently, we compared the abilities of extravascular and intravascular cells to support fibrin formation, structure, and stability. Extravascular cells (fibroblasts, smooth muscle) supported formation of dense fibrin networks that resisted fibrinolysis, whereas unstimulated intravascular (endothelial) cells produced coarse networks that were susceptible to fibrinolysis. All 3 cell types produced a fibrin structural gradient, with a denser network near, versus distal to, the cell surface. Although fibrin structure depended on cellular procoagulant activity, it did not reflect interactions between integrins and fibrin. These findings contrasted with those on platelets, which influenced fibrin structure via interactions between beta 3 integrins and fibrin. Inflammatory cytokines that induced prothrombotic activity on endothelial cells caused the production of abnormally dense fibrin networks that resisted fibrinolysis. Blocking tissue factor activity significantly reduced the density and stability of fibrin networks produced by cytokine-stimulated endothelial cells. Together, these findings indicate fibrin structure and stability reflect the procoagulant phenotype of the endogenous cells, and suggest abnormal fibrin structure is a novel link between inflammation and thrombosis. (Blood. 2009; 114:4886-4896)