TISSUE FACTOR ACTIVATION OF FACTOR X MEDIATED BY FLOW

描述（改编自研究者摘要）：长期目的 这项研究建议的目的是更好地了解 血管细胞调节促凝血活性的流体流动 暴露在流动的血液中 具体而言，这些研究将审查 流体流动产生的机械力的能力， 调节组织因子（TF）介导的血液循环途径的活性 凝血 使用精确设计的平行板流动室， 流体剪切速率对培养的人平滑肌组织TF表达的影响 将研究肌肉细胞。 使用管状流的类似研究 反应器，其内部已经用含TF的磷脂涂覆 将进行双层。 TF活性水平将从 测量因子X的产生。此外， TF活性的调节将通过测量TF mRNA来检查， 培养细胞 为了将实验结果与 理论上的考虑，计算程序将被用来解决 适当的流体动力学和质量传输方程，并生成 流动室内的速度和剪切速率分布。 各种系统的实验结果将与 理论预测，以准确定义的性质， 运输促凝蛋白的表面，以及变化 的动力学参数，Km和Vmax，在不同的流动条件下。 这些参数对流动的依赖性和流动的直接激活 在血管细胞上表达的组织因子的表达是特别感兴趣的， 这次调查 这些实验技术的结合， 计算分析将提供有关 流体流动影响促凝血活性的机制 血管细胞，因此，将有助于了解 TF介导的血液凝固在生理和病理生理条件下 流动条件

DESCRIPTION (Adapted from Investigator's Abstract): The long-term objective of this research proposal is to develop a better understanding of the role of fluid flow in the regulation of procoagulant activity by vascular cells exposed to flowing blood. Specifically, these studies will examine the ability of mechanical forces generated as a consequence of fluid flow to modulate the activity of the tissue factor (TF)-mediated pathway of blood coagulation. Using precisely designed parallel-plate flow chambers, the effects of fluid shear rate on the expression of TF by cultured human smooth muscle cells will be investigated. Similar studies using a tubular flow reactor whose interior has been coated with a TF-containing phospholipid bilayer will be performed. The levels of TF activity will be assessed from measurements of the production of Factor X. Additionally, the nature of the regulation of TF activity will be examined from measurements of TF mRNA in cultured cells. In order to correlate experimental findings with theoretical considerations, computational routines will be employed to solve the appropriate fluid dynamic and mass transport equations and generate the velocity and shear rate profiles within the flow chambers. The experimental results for the various systems will be compared with theoretical predictions in order to precisely define the nature of the transport of procoagulant proteins to the surface, as well as the variation of the kinetic parameters, Km and Vmax, under differing flow conditions. The dependence of these parameters on flow and the direct activation by flow of tissue factor expressed on vascular cells are of particular interest in this investigation. The combination of these experimental techniques and computational analyses will provide extensive information regarding the mechanism(s) by which fluid flow influences the procoagulant activity of vascular cells and will therefore, contribute to the understanding of TF-mediated blood coagulation under both physiologic and pathophysiologic flow conditions.