Endothelial cells organize fibrin clots into structures that are more resistant to lysis
Endothelial cells organize fibrin clots into structures that are more resistant to lysis
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DOI：
10.1017/s143192760505052x
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发表时间：
2005-06-01
影响因子：
2.8
通讯作者：
Hantgan, RR
中科院分区：
文献类型：
--
作者：
Jerome, WG;Handt, S;Hantgan, RR
急性心肌梗死是美国死亡和残疾的主要原因。将血栓溶解剂引入凝块中以溶解闭塞性冠状动脉血栓是一种治疗方法。然而，尽管我们对血栓形成和溶栓的认识有了进步，溶栓治疗后的生存率并没有实质性的提高。这一失败突出了需要进一步研究的因素介导的凝块稳定。使用激光扫描共聚焦显微镜从荧光素标记的纤维蛋白原形成的凝块，我们研究了什么样的影响纤维蛋白结合到内皮细胞表面上的凝块结构和耐溶解。在人脐静脉内皮细胞（HUVEC）上产生荧光纤维蛋白凝块，并分析凝块结构。在HUVEC的存在下，内皮表面附近的纤维蛋白更有组织，发生在更紧密的束相比，纤维蛋白仅50 μ m以上。HUVEC对纤维蛋白结构的影响被α（V）或163整联蛋白亚基的抑制浓度的抗体阻断。与内皮细胞相关的凝块区域比内皮远端更均匀的区域更耐溶解。因此，我们的数据表明，纤维蛋白与内皮表面上的整合素结合产生对溶解更有抵抗力的凝块。
Acute myocardial infarction is a major cause of death and disability in the United States. Introducing thrombolytic agents into the clot to dissolve occlusive coronary artery thrombi is one method of treatment. However, despite advances in our knowledge of thrombosis and thrombolysis, survival rates following thrombolytic therapy have not improved substantially. This failure highlights the need for further study of the factors mediating clot stabilization. Using laser scanning confocal microscopy of clots formed from fluorescein-labeled fibrinogen, we investigated what effect binding of fibrin to the endothelial surface has on clot structure and resistance to lysis. Fluorescent fibrin clots were produced over human umbilical vein endothelial cells (HUVEC) and the clot structure analyzed. In the presence of HUVEC, fibrin near the endothelial surface was more organized and occurred in tighter bundles compared to fibrin just 50 mu m above. The HUVEC influence on fibrin architecture was blocked by inhibitory concentrations of antibodies to alpha(V) or 163 integrin subunits. The regions of the clots associated with endothelial cells were more resistant to lysis than the more homogenous regions distal to endothelium. Thus, our data show that binding of fibrin to integrins on endothelial surfaces produces clots that are more resistant to lysis.