ROLE OF BLOOD/VESSEL WALL COMPONENTS IN THROMBOSIS

本提案的总体目标是确定 与血管相互作用的血液基本成分的血液流动 血栓形成过程中的表面。 血小板的沉积， 剥脱内皮的血管节段上的蛋白质物质 内衬将在一个环形灌注系统下进行研究， 血管内遇到的剪切条件范围。 全血将 通过各种技术制备：（1）在柠檬酸盐抗凝剂中，（2）天然的， 无抗凝剂，（3）用各种细胞和 血液的蛋白质部分，和（4）再钙化以允许活化 凝血系统。 这些血液将暴露于各种类型的 血管段：（1）储存在缓冲液中的兔、人和猪血管，（2） 新鲜制备的血管，（3）用选择的抗体处理的血管， 内皮下成分，和（4）缺乏成分的血管， 血管性血友病因子（VWF）。 血管表面与 纤维蛋白和血小板将使用形态测定方法定量， 评价 纤维蛋白原活化与血小板释放 血液中流过血管段的颗粒状物质 将通过放射免疫分析测量并与形态计量学相关 结果 特别强调将放在调查冯维勒布兰德的作用 与血小板相互作用有关的VWF因子 血管内皮下与血小板血栓的生长和稳定性 利用一组独特的患者， VWD的亚型。 血流对血浆VWF功能的影响 通过血液扩散，在内皮下表面结合， 血管壁VWF将与其影响能力有关 血小板-内皮下相互作用。 血小板的潜在重要性 VWF介导血小板-血小板聚集的发展 将通过使用具有不同水平的 血小板VWF和研究严重VWD患者输血后， VWF。 血管壁VWF多聚体的大小分布，它们的表达能力， 多聚化及其在血小板与内皮细胞结合中的作用 还将研究内皮下。

The overall objective of this proposal is to determine the influence of blood flow on the basic components of blood which interact with vascular surfaces in the process of thrombosis. The deposition of platelets and proteinaceous material on vessel segments denuded of their endothelial lining will be investigated in an annular perfusion system under the full range of shear conditions encountered intravascularly. Whole blood will be prepared by various techniques: (1) in citrate anticoagulant, (2) native, without anticoagulant, (3) reconstituted with various cellular and proteinaceous fractions of blood, and (4) re-calcified to permit activation of the coagulation system. This blood will be exposed to various types of vascular segments: (1) rabbit, human and pig vessels stored in buffer, (2) freshly prepared vessels, (3) vessels treated with antibodies to selected elements of subendothelium, and (4) vessels deficient in components such as von Willebrand's factor (VWF). The interaction of the vessel surface with fibrin and platelets will be quantified using a morphometric means of evaluation. The activation of fibrinogen and the release of platelet granular material in the blood which has passed over the vascular segments will be measured by radio-immuno assay and correlated with the morphometric results. Special emphasis will be placed on investigating the role of von Willebrand factor (VWF) with respect to the interaction of platelets with subendothelium and the growth and stability of platelet thrombi on vessel walls utilizing a unique group of patients with various well-defined subtypes of VWD. The influence of blood flow on the ability of plasma VWF to diffuse through blood, bind at the subendothelial surface and associate with vessel wall VWF will be related to its ability to influence platelet-subendothelial interaction. The potential importance of platelet VWF in mediating the development of platelet-platelet aggregation on subendothelium will be assessed by using patients with varying levels of platelet VWF and by studying patients with severe VWD after transfusion of VWF. The size distribution of vessel wall VWF multimers, their ability to multimerize on subendothelium and their role in platelet binding to subendothelium will also be investigated.