Thrombi produced in stagnation point flows have a core-shell structure.

Thrombi produced in stagnation point flows have a core-shell structure.
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DOI:
10.1007/s12195-017-0503-x
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发表时间:
2017-12
影响因子:
2.8
通讯作者:
Diamond SL
Diamond SL
中科院分区:
工程技术4区
文献类型:
--
作者:
Herbig BA;Diamond SL

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在病变动脉内的血流分离/再附着区域,局部血流动力学可导致停滞点血流,这为动脉粥样硬化提供了一个不典型的环境。撞击血流发生在冠状动脉狭窄或病变的颈动脉分叉的远端。通过直接垂直于纤维性胶原蛋白血栓表面灌注全血,微流体装置产生了一个滞止点流动。在这个实验中,血栓形成的侧视图可视化允许在不同的流速和血液生化条件下观察血栓的结构和组成。对于在胶原/组织因子表面上的凝血,在该装置中形成的血小板血栓显示出一种核-壳结构,具有富含纤维蛋白的血小板p -选择素阳性核心和外层血小板p -选择素阴性外壳。在低、高剪切血凝块中均检测到VWF,但在全血中加入n -乙酰半胱氨酸后,在低、高剪切血凝块中血小板和VWF沉积均明显减少。为了进一步研究凝块稳定性的来源,加入1mm GPRP来阻止纤维蛋白的形成,同时允许凝血酶的par1 /4切割活性继续进行。抑制纤维蛋白聚合并没有改变血块的整体结构,表明这些血块在没有纤维蛋白的情况下是稳定的。冲击流微流体产生具有核壳结构的血栓。
In regions of flow separation/reattachment within diseased arteries, the local hemodynamics can result in stagnation point flow that provides an atypical environment in atherosclerosis. Impinging flows occur with recirculation eddies distal of coronary stenosis or diseased carotid bifurcations. By perfusing whole blood directly perpendicular to a fibrillar collagen thrombotic surface, a microfluidic device produced a stagnation point flow. Side view visualization of thrombosis in this assay allowed for observation of clot structure and composition at various flow rates and blood biochemistry conditions. For clotting over collagen/tissue factor surfaces, platelet thrombi formed in this device displayed a core-shell architecture with a fibrin-rich, platelet P-selectin-positive core and an outer platelet P-selectin-negative shell. VWF was detected in clots at low and high shear, but when N-acetylcysteine was added to the whole blood, both platelet and VWF deposition were markedly decreased at either low or high flow. To further examine the source of clot stability, 1 mM GPRP was added to prevent fibrin formation while allowing the PAR1/4-cleaving activity of thrombin to progress. The inhibition of fibrin polymerization did not change the overall structure of the clots, demonstrating the stability of these clots without fibrin. Impinging flow microfluidics generate thrombi with a core-shell structure.
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