TISSUE FACTOR ACTIVATION OF FACTOR X MEDIATED BY FLOW

血流介导的组织因子 X 因子激活

• 批准号: 2667416
• 负责人: VINCENT T. TURITTO
• 金额: $ 9.79万
• 依托单位: UNIVERSITY OF MEMPHIS
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-30 至 2001-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2667416
• 关键词: blood coagulation; coagulation factor X; fluid flow; gene expression; messenger RNA; thromboplastin; tissue /cell culture; vascular endothelium

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.

描述（改编自研究者摘要）：长期目标

项目成果

Active tissue factor shed from human arterial smooth muscle cells adheres to artificial surfaces.

从人动脉平滑肌细胞脱落的活性组织因子粘附在人造表面上。

• DOI: 10.1163/156856200744282
• 发表时间: 2000
• 期刊: Journal of biomaterials science. Polymer edition
• 作者: Hathcock,JJ;Hall,CL;Turitto,VT
• 通讯作者: Turitto,VT