SCCOR in Hemostatic and Thrombotic Diseases

描述(由申请人提供)： 血栓形成是一个多因素的过程，直接导致了美国近一半的死亡率。现在人们普遍认识到，胰岛素抵抗和2型糖尿病(DM)，通常在肥胖的背景下，经常被认为是动脉血栓形成现象的促成因素，并构成该应用的一个主要主题。所有这些项目都包括系统地研究糖尿病和/或胰岛素抵抗对血栓形成的影响。这是因为最新数据估计，美国有1820万人患有糖尿病，另有4000万人可能患有糖耐量减退或“糖尿病前期”。该SCCOR的组件项目涉及血栓形成的遗传、细胞和分子机制。从机制上讲，这一应用针对的是导致血栓形成的三个主要系统，包括血小板激活、凝血酶生物学和蛋白酶激活受体(PARs)以及纤溶系统。这项研究计划将研究人员聚集在一起，用不同的和互补的方法来测试涉及血栓形成机制和如何防止这一过程的假设。所有项目都包括直接涉及人类受试者的目标。事实上，在五个不同的项目中提出的18个独特的具体目标中，有12.5个(69.4%)涉及以患者为中心的研究。研究人员在纤溶、G蛋白与受体的偶联、二十烷类代谢、血小板胶原受体和糖尿病方面的综合技能已被合并为一个动态合作研究小组，该小组将促进我们对这些高危人群中动脉血栓形成的分子机制的理解。

DESCRIPTION (provided by applicant): Thrombosis is a multifactorial process that directly contributes to nearly half of the mortality in the United States. It is now widely appreciated that insulin resistance and Type 2 Diabetes Mellitus (DM), often in the setting of obesity, are frequently identified as contributors to the development of arterial thrombotic phenomena, and comprise a major theme of this application. All of the Projects include Aims that systematically investigate the impact of diabetes and/or insulin resistance on thrombosis. This is motivated by the most recent data estimate that 18.2 million individuals in the United States have DM and a further 40 million may have impaired glucose tolerance or "pre-diabetes". The component projects of this SCCOR address genetic, cellular and molecular mechanisms of thrombosis. In a mechanistic sense, this application targets three of the pre-eminent systems that contribute to the development of thrombosis, including platelet activation, thrombin biology and protease activated receptors (PARs), and the fibrinolytic system. This research program brings together investigators with diverse and complementary approaches to test hypotheses involving the mechanisms of thrombosis and how this process can be prevented. All of the Projects include Aims that directly involve human subjects. In fact, 12.5 of the 18 (69.4%) unique Specific Aims proposed in the five distinct Projects involve patient-oriented research. The combined skills of the investigators in fibrinolysis, the coupling of G-proteins to receptors, eicosanoid metabolism, platelet collagen receptors, and diabetes have been merged into a dynamic collaborative research group that will advance our understanding of the molecular mechanisms of arterial thrombosis in these high risk populations.