SCCOR in Hemostatic and Thrombotic Diseases

血栓形成是一个多因素的过程，直接导致美国近一半的死亡率。现在广泛认识到，胰岛素抵抗和2型糖尿病（DM），通常在肥胖的情况下，经常被认为是动脉血栓形成现象发展的贡献者，并且构成本申请的主要主题。所有项目都包括系统研究糖尿病和/或胰岛素抵抗对血栓形成的影响的目标。这是由最新的数据估计，在美国有1820万人患有DM，另外4000万人可能患有葡萄糖耐量受损或“前驱糖尿病”。该SCCOR的组成项目涉及血栓形成的遗传、细胞和分子机制。在机械学意义上，本申请靶向三个促成血栓形成的突出系统，包括血小板活化、凝血酶生物学和蛋白酶活化受体（PAR）以及纤维蛋白溶解系统。该研究项目汇集了具有不同和互补方法的研究人员，以测试涉及血栓形成机制以及如何预防这一过程的假设。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%）涉及以患者为导向的研究。研究人员在纤维蛋白溶解、G蛋白与受体偶联、类花生酸代谢、血小板胶原受体和糖尿病方面的综合技能已经合并成一个动态的合作研究小组，这将促进我们对这些高危人群动脉血栓形成分子机制的理解。

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.