Genetic and Cellular Determinants of Arterial Thrombosis

动脉血栓形成作为心肌梗死、中风和肢体坏疽的近因， 是美国最重要的死亡和发病原因。血小板在启动 动脉血栓该SCCOR的总体目标是发现改变的遗传和细胞决定因素。 血小板在全身炎症状态中的功能，如动脉粥样硬化和糖尿病。我们已经组建 一个由临床、基础和转化科学家组成的多学科团队，并建立了一个拥有6名科学家的中心。 项目和6个核心。项目1将使用体外分析、体内小鼠遗传模型和人类遗传模型。 一项研究旨在检验血小板糖蛋白CD 36介导血小板高反应性的新假设 与动脉粥样硬化、糖尿病和炎症有关。项目2将探索一个至关重要的 临床问题，血小板对药物干预的耐药性，并将利用靶向人类遗传 方法结合复杂的体外血小板功能评估。项目3将探索 血小板活化因子（PAF）在介导炎症和炎症反应之间的界面中的机制作用 血栓形成项目4将研究接受血管内颈动脉支架植入术的临床患者人群， 易损斑块模型，专注于开发新的成像工具和生物标志物。项目5将 研究白细胞-血小板相互作用，重点是Mac-1整合素在调节血栓形成中的作用。 项目6将研究抗磷脂综合征患者，这是一种自身免疫性疾病， 血栓形成的原因，特别是在年轻女性，以表征血栓形成风险的决定因素。核心A将 提供行政支持、核心B生物统计支持和核心C基础设施，以支持 所有6个项目的临床研究部分。核心D将提供高通量人类基因分型 核心E流式细胞仪和质谱服务。核心F将提供一个课程， 为SCCOR实验室临床血栓形成研究培训医生提供职业发展支持。

Arterial thrombosis as the proximate cause of myocardial infarction, stroke, and limb gangrene remains the most important cause of mortality and morbidity in the USA. Blood platelets play a critical role in initiating arterial thrombi. The overall goal of this SCCOR is to discover genetic and cellular determinants of altered platelet function in systemic inflammatory states, such as atherosclerosis and diabetes. We have assembled a multidisciplinary team of clinical, basic and translational scientists and developed a Center with 6 scientific projects and 6 cores. Project 1 will use in vitro assays, in vivo mouse genetic models, and human genetic studies to examine the novel hypothesis that platelet glycoprotein CD36 mediates platelet hyper-reactivity associated with atherosclerosis, diabetes, and inflammation. Project 2 will explore a critically important clinical problem, platelet resistance to pharmacologic interventions, and will utilize a targeted human genetic approach coupled to sophisticated in vitro assessment of platelet function. Project 3 will explore the mechanistic role of platelet activating factor (PAF) in mediating the interface between inflammation and thrombosis. Project 4 will study a clinical population of patients undergoing endovascular carotid stenting as a model of the vulnerable plaque, focusing on developing novel imaging tools and biomarkers. Project 5 will study leukocyte-platelet interactions, focusing on the role of the Mac-1 integrin in regulating thrombosis. Project 6 will study patients with anti-phospholipid syndrome, an autoimmune disease that is an important cause of thrombosis, especially in young women, to characterize determinants of thrombotic risk. Core A will provide administrative support, Core B biostatistics support and Core C an infrastructure to support the clinical research components of all 6 projects. Core D will provide high throughput human genotyping services and Core E flow cytometry and mass spectrometry services. Core F will provide a curriculum and career development support for physicians training in clinical thrombosis research in SCCOR laboratories.