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Reaction and Transport Dynamics in Human Blood

人体血液中的反应和运输动力学

基本信息

批准号：
7591686
负责人：
SCOTT L DIAMOND
金额：
$ 22.54万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
1996
资助国家：
美国
起止时间：
1996-07-15 至 2011-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7591686
关键词：
Actins Active Sites Address Adhesions Adhesives Angioplasty Binding Biochemical Biochemistry Biological Assay Biology Blood Blood Cells Blood Clot Blood Platelets Blood Vessels Blood coagulation Blood flow C3bi Caliber Cardiopulmonary Bypass Cathepsin G Cell Adhesion Cell surface Cells Cellular Membrane Clinical Coagulation Process Collagen Complex Convection Data Deep Vein Thrombosis Deposition Detection Diagnostic Diagnostic Procedure Diamond Diffusion Disease Progression Drug Delivery Systems Elastases Embolism Equation Erythrocytes Event Factor IXa Fibrin Fibrinogen Fluorescence Fluorogenic Substrate Genetic Programming Genotype Guanine Nucleotide Dissociation Inhibitors Hemorrhage Heterogeneity Human Image In Vitro Individual Inflammation Integrins Intercellular adhesion molecule 1 Kinetics L-Selectin Life Ligands Measures Mediating Membrane Modeling Molecular Probes P-Selectin Pathogenesis Pathology Pathway interactions Patients Phenotype Plasma Predisposition Prevention Printing Process Proteins Pseudo von Willebrand disease Pulmonary Embolism Reaction Regression Analysis Regulation Research Research Personnel Resolution Rest Reticulocytes Risk Role Simulate Solutions Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization Speed Stroke Structure Surface Testing Thrombin Thromboplastin Thrombosis Transport Reaction Venous Video Microscopy Whole Blood Work Wound Healing Zea mays trypsin inhibitor base cofactor computerized tools depressed factor IXa-factor VIIIa hemodynamics improved insight millisecond molecular dynamics neutrophil novel polymerization programs receptor research study restenosis simulation von Willebrand Factor

项目摘要

DESCRIPTION (provided by applicant): In the context of a given genotype and phenotype, the dynamics of blood clot assembly ultimately dictate: thrombosis; thrombolytic susceptibility of clots; stroke during cardiopulmonary bypass; restenosis after angioplasty; wound healing/inflammation; and pathogenesis of deep vein thrombosis or pulmonary embolism. During blood coagulation, activated platelets and neutrophils form homotypic and heterotypic aggregates through over ten receptor-mediated pathways while triggering thrombin formation and fibrin polymerization. Yet less is known quantitatively about the strengths and kinetics of platelet-platelet and platelet-neutrophil bonding that leads to aggregation or deposition under coagulating whole blood flow conditions or the biochemical reactivity of these aggregates. Furthermore, temporal resolution of events lasting only a few milliseconds is rarely achieved in most experiments. In vitro high speed imaging experiments will utilize human blood cells and proteins for kinetic studies of these interactions under controlled hemodynamic and coagulation conditions. Kinetic data from these experiments will be used to gain improved mechanistic understanding of human blood phenomena. By defining the molecular dynamics of how blood clots are assembled under flow conditions as well as defining the flow-regulation of various clotting scenarios, the risks of unregulated clotting, bleeding, and embolism will be more quantitatively understood for a given disease progression. Specific aims are: Aim 1 Platelet and neutrophil receptor interactions during thrombosis; Aim 2 Coagulation initiation on activated platelets; Aim 3 Red blood cell adhesion mechanisms in a depressed venous flow model of deep vein thrombosis; and Aim 4 Computational tools for aggregation and coagulation research. Overall, these studies seek to provide fundamental insight into cell-cell interacitions and coagulation biochemistry that occur under flow.

描述（由申请人提供）：在给定基因型和表型的背景下，血凝块组装的动力学最终决定：血栓形成;凝块的血栓溶解易感性;心肺转流术期间的卒中;血管成形术后的再狭窄;伤口愈合/炎症;以及深静脉血栓形成或肺栓塞的发病机制。在凝血过程中，活化的血小板和中性粒细胞通过十多个受体介导的途径形成同型和异型聚集体，同时触发凝血酶形成和纤维蛋白聚合。然而，对血小板-血小板和血小板-中性粒细胞结合的强度和动力学的定量了解较少，这些结合导致在全血流动条件下的聚集或沉积或这些聚集体的生化反应性。此外，在大多数实验中，持续仅几毫秒的事件的时间分辨率很少实现。体外高速成像实验将利用人血细胞和蛋白质在受控的血液动力学和凝血条件下进行这些相互作用的动力学研究。从这些实验中获得的动力学数据将用于获得更好的人体血液现象的机械理解。通过定义血液凝块在流动条件下如何组装的分子动力学以及定义各种凝血情况的流动调节，对于给定的疾病进展，将更定量地了解不受调节的凝血、出血和栓塞的风险。具体目标是：目的1血栓形成过程中血小板和中性粒细胞受体的相互作用;目的2激活血小板的凝血启动;目的3深静脉血栓形成的静脉血流抑制模型中的红细胞粘附机制;目的4聚集和凝血研究的计算工具。总的来说，这些研究试图提供基本的洞察细胞-细胞相互作用和凝血生化下发生的流动。