Thrombus Formation In Vivo

体内血栓形成

• 批准号: 7347100
• 负责人: Bruce Furie
• 金额: $ 179.99万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2013-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7347100
• 关键词: Thrombus; Formation; Vivo

DESCRIPTION (provided by applicant): This Program Project Grant, entitled "THROMBUS FORMATION IN VIVO" brings four principal investigators to focus on the process of thrombogenesis. This group has pioneered the development of high speed intravital confocal and widefield microscopy to study thrombus formation in a living mouse using the laser induced thrombosis model. Using this technology, they will address a series of critical questions related to the three phases of thrombus formation: initiation, development and propagation. In Project #1 entitled TISSUE FACTOR AND THE INITIATION OF THROMBUS FORMATION, Dr. Bruce Furie will study the physiologic role of tissue factor and the molecular basis of tissue factor activation. He will examine the kinetics of expression of tissue factor forms in cultured endothelial cells and during thrombus formation in a living mouse. The cellular source of tissue factor required during thrombus formation will be evaluated using chimeric mice, MAFIA mice, and genetically altered mice that are deficient in tissue factor in endothelial cells, platelets, myeloid cells or smooth muscle cells. In Project #2 entitled PLATELET PROTEIN PALMITOYLATION AND THROMBUS FORMATION, Dr. Robert Flaumenhaft will evaluate the role of protein palmitoylation in platelet activation and thrombus formation using the mouse thrombosis model, and determine which proteins undergo posttranslational palmitoylation. In Project #3 entitled CD39 AND ITS ROLE IN THROMBOGENESIS, Dr. Simon Robson will test the hypothesis that modulated CD39/NTPDase-1 expression regulates nucleotide-mediated signaling in the vasculature and platelet activation, thus regulating thrombus propagation during thrombus formation in living mice. In Project #4 entitled INITIAL PLATELET ADHESION AND THROMBUS PROPAGATION, Dr. Barbara Furie will study the combined roles of GPVI/PAR4 and PAR4/von Willebrand factor in platelet activation during thrombus formation, the contribution of cellular sources of von Willebrand factor to thrombus development and the role of Factor XII and Factor IX in tissue factor-mediated thrombus propagation. Administrative, Intravital Microscopy and Mass Spectrometry cores support the activities of the four projects. The ability to study the biochemistry and cell biology of thrombus formation in living animals offers opportunities to understand thrombosis and develop strategies for preventing thrombosis, the major cause of morbidity and mortality in Western society.

描述（由申请人提供）： 该计划项目赠款的标题为“体内的血栓形成”，使四名主要研究人员专注于血栓形成过程。该小组率先开发了使用激光诱导的血栓形成模型在活小鼠中研究活小鼠中的血栓形成的高速浸润性聚焦和广场显微镜的发展。使用这项技术，他们将解决与血栓形成的三个阶段有关的一系列关键问题：启动，开发和传播。在项目＃1的标题为“组织因子”和“血栓形成的开始”中，布鲁斯·弗里（Bruce Furie）博士将研究组织因子的生理作用和组织因子激活的分子基础。他将检查培养的内皮细胞中组织因子表达的动力学以及活小鼠的血栓形成过程。将使用嵌合小鼠，黑手党小鼠以及在内皮细胞，血小板，髓样细胞或平滑肌细胞中缺乏组织因子的遗传因子的小鼠，将评估血栓形成过程中所需的组织因子的细胞来源。在标题为“血小板蛋白质棕榈酰化和血栓形成”的项目2中，Robert Flaumenhaft博士将使用小鼠血栓形成模型评估蛋白质棕榈酰化在血小板激活和血栓形成中的作用，并确定哪些蛋白质经历了变质后棕榈酰化。在标题为CD39及其在血栓形成中的作用的项目＃3中，Simon Robson博士将测试以下假设：调节CD39/NTPDase-1表达调节血管和血小板激活中核苷酸介导的信号传导，从而调节活鼠的血栓形成过程中的血栓传播。 In Project #4 entitled INITIAL PLATELET ADHESION AND THROMBUS PROPAGATION, Dr. Barbara Furie will study the combined roles of GPVI/PAR4 and PAR4/von Willebrand factor in platelet activation during thrombus formation, the contribution of cellular sources of von Willebrand factor to thrombus development and the role of Factor XII and Factor IX in tissue factor-mediated thrombus propagation.行政，内部显微镜和质谱核心支持这四个项目的活动。研究活体动物中血栓形成的生物化学和细胞生物学的能力提供了理解血栓形成并制定预防血栓形成的策略，这是西方社会发病和死亡率的主要原因。