TISSUE FACTOR, THROMBOSIS AND THE ARTERIAL WALL

组织因子、血栓形成和动脉壁

• 批准号: 6216332
• 负责人: Yale R Nemerson
• 金额: $ 187.94万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-03-01 至 2006-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6216332
• 关键词: thromboplastin; thrombosis

This is a competitive renewal of a SCOR in Hemostatic and Thrombotic Diseases by a highly-interactive group of investigators at the Mount Sinai School of Medicine. The program is comparised of 5 projects and 3 cores. Findings by the SCOR investigators and other laboratories have established the presence of circulating tissue factor (TF). Our program, in particular has demonstrated that this TF is active and can initiate thrombus formation. The project of Dr. Fuster will measure circulating TF in patients with risk factors for atherosclerosis and thrombosis and will examine the effect of risk factor reduction on TF levels and thrombogenicity. Dr. Fuster has found collaborations with investigators that will provide samples from several important clinical studies. Dr. Nemerson's project will explore the novel finding that leukocytes can transfer TF to the surface of platelets and will attempt to identify the platelet "TF receptor." Based on the finding that large thrombi stain diffusely the TF, Dr. Nemerson will develop mathematical models to examine the diffusion of molecules within the thrombus. Dr. Taubman's project will study the role of smooth muscle cells (SMC) and cardiomyocytes in releasing TF into the microcirculation after angioplasty and myocardial infarction. He will employ pig models of coronary artery injury and infarction and novel transgenic mice in which TF is conditionally knocked out in SMC and cardiomyocytes to examine the role of TF in mediating infarct size and intimal hyperplasia. These closely- linked projects promise to establish new paradigms for TF generation and biology. A second major focus of the SCOR is on platelet-leukocyte interactions. The project of Dr. Harpel will examine the role of I-309, a CC-chemokine, in regulating leukocyte accumulation in arterial injury. His findings that platelets possess I-309 has led to the novel hypothesis that the release of I-309 by platelets accumulating at the site of injury is critical to the early recruitment of leukocytes. He will also examine the role of I-309 in mediating endothelial cell migration and vasculogenesis. Dr. Coller's project will undertake a detailed examination of the interaction between leukocytes and platelets in regulating arterial thrombosis and leukocyte transmigration. His project involves several recently-developed models of thrombosis and novel transgenic animals. In support of this project will be a Pathology Core, a Thrombosis Core.

这是西奈山医学院一个高度互动的研究小组对止血和血栓性疾病的SCOR进行的竞争性更新。 该方案是比较5个项目和3个核心。SCOR研究人员和其他实验室的发现已经确定了循环组织因子（TF）的存在。 我们的项目，特别是已经证明，这种TF是活跃的，可以启动血栓形成。Fuster博士的项目将测量具有动脉粥样硬化和血栓形成风险因素的患者的循环TF，并将检查风险因素减少对TF水平和血栓形成的影响。 Fuster博士已经找到了与研究人员的合作，这些研究人员将提供来自几项重要临床研究的样本。 Nemerson博士的项目将探索新的发现，即白细胞可以将TF转移到血小板表面，并试图识别血小板的TF受体。“基于大血栓对TF扩散染色的发现，Nemerson博士将开发数学模型来检查血栓内分子的扩散。 Taubman博士的项目将研究血管成形术和心肌梗死后平滑肌细胞（SMC）和心肌细胞在释放TF进入微循环中的作用。 他将采用猪冠状动脉损伤和梗死模型和新型转基因小鼠，其中TF在SMC和心肌细胞中被条件性敲除，以研究TF在介导梗死面积和内膜增生中的作用。 这些紧密相连的项目有望为TF的产生和生物学建立新的范例。 SCOR的第二个主要焦点是血小板-白细胞相互作用。 Harpel博士的项目将研究I-309（一种CC趋化因子）在调节动脉损伤中白细胞积聚中的作用。 他发现血小板具有I-309，这一发现导致了新的假设，即在损伤部位聚集的血小板释放I-309对白细胞的早期募集至关重要。 他还将研究I-309在介导内皮细胞迁移和血管生成中的作用。 Coller博士的项目将详细研究白细胞和血小板在调节动脉血栓形成和白细胞迁移中的相互作用。 他的项目涉及几个最近开发的血栓形成模型和新型转基因动物。 支持该项目的将是病理学核心，血栓形成核心。