Ex Vivo and In Vivo Models of Hemostasis and Thrombosis Core

止血和血栓核心的体外和体内模型

• 批准号: 7029350
• 负责人: Zaverio M Ruggeri
• 金额: $ 44.09万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7029350
• 关键词: biological models; biomedical facility; blood coagulation; clinical research; hemodynamics; hemostasis; human tissue; laboratory mouse; model design /development; thrombosis

The purpose of core A is to provide investigators in the Program Project with access to standardized procedures for the study and quantitative description of processes relevant to thrombus formation under the influence of defined flow forces, in ex vivo models or within the circulatory system of a whole animal. Moreover, the core will help investigators with the isolation and/or culture of relevant vascular cells under static and flow conditions. Project 1 (Ruggeri) will utilize ex vivo perfusion chambers to study the volume of thrombi deposited on selected thrombogenic substrates, including different types of purified collagens and different extracellular matrices (ECMs) under conditions mimicking different hemodynamic environments. Project 1 will utilize intravital microscopy techniques to study thrombus formation in different mice with targeted alterations of platelet and matrix proteins. Project 1 will use 40% of core A resources. Project 2 (Ginsberg) will utilize the core service to isolate endothelial cells from mice with targeted mutations of proteins relevant to fibronectin matrix assembly and will study the effect of shear forces on the structure and thrombogenicity of deposited ECM. Project 2 will also study the effects of inhibitors of specific signaling pathways on the alignment of stress fibers in endothelial cells exposed to shear stress, and the possible related changes in matrix thrombogenicity. Project 2 will use 15% of core A resources. Project 3 (Ruf) will study several aspects of tissue factor (TF) functional modulation using endothelial cells and fibroblasts prepared in core A. Specifically, project 3 will examine the mechanisms through which TF becomes associated with ECM, and whether cryptic TF in matrices becomes active through oxidation. Project 3 will use 15% of core A resources. Project 4 (Griffin) will use intravital videomicroscopy to study the antithrombotic properties of wild type and mutant activated protein C. Project 4 will use 30% of core A resources.

核心A的目的是为计划项目中的研究者提供标准化的 血栓形成相关过程的研究和定量描述程序 在离体模型中或在整个动物的循环系统中，确定的流动力的影响。 此外，该核心将帮助研究人员分离和/或培养相关的血管细胞， 静态和流动条件。项目1（Ruggeri）将利用离体灌注室研究 沉积在选定的血栓形成基质上的血栓，包括不同类型的纯化胶原， 不同的细胞外基质（ECM）在模拟不同的血液动力学环境的条件下。 项目1将利用活体显微镜技术研究不同小鼠的血栓形成， 靶向改变血小板和基质蛋白。项目1将使用核心A资源的40%。计划2 （金斯伯格）将利用核心服务，从具有靶向突变的小鼠中分离内皮细胞， 与纤连蛋白基质组装相关的蛋白质，并将研究剪切力对结构的影响， 沉积ECM的血栓形成性。项目2还将研究特定信号传导抑制剂的作用 在内皮细胞中暴露于剪切应力的应力纤维排列的途径，以及可能的 基质促凝性的相关变化。项目2将使用核心A资源的15%。项目3（Ruf）将 利用内皮细胞和成纤维细胞研究组织因子（TF）功能调节的几个方面 在核心A中制备。具体而言，项目3将审查信托基金成为 与ECM相关，以及基质中隐藏的TF是否通过氧化变得活跃。项目3将 使用15%的核心A资源。项目4（格里芬）将使用活体视频显微镜研究 野生型和突变型活化蛋白C的抗血栓形成特性。项目4将使用核心A的30% 资源