SCCOR in Hemostatic and Thrombotic Diseases

SCCOR 在止血和血栓性疾病中的应用

• 批准号: 7808876
• 负责人: JOHN Alexander OATES
• 金额: $ 339.22万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-20 至 2012-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7808876
• 关键词: SCCOR; Hemostatic; Thrombotic; Diseases

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.

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。

项目成果

Protein kinase C regulation of 12-lipoxygenase-mediated human platelet activation.

蛋白激酶 C 对 12-脂氧合酶介导的人血小板活化的调节。

• DOI: 10.1124/mol.111.075630
• 发表时间: 2012
• 期刊: Molecular pharmacology
• 影响因子: 3.6
• 作者: Yeung,Jennifer;Apopa,PatrickL;Vesci,Joanne;Kenyon,Victor;Rai,Ganesha;Jadhav,Ajit;Simeonov,Anton;Holman,TheodoreR;Maloney,DavidJ;Boutaud,Olivier;Holinstat,Michael
• 通讯作者: Holinstat,Michael

12-lipoxygenase activity plays an important role in PAR4 and GPVI-mediated platelet reactivity.

12-脂氧合酶活性在 PAR4 和 GPVI 介导的血小板反应性中发挥重要作用。

• DOI: 10.1160/th13-01-0014
• 发表时间: 2013
• 期刊: Thrombosis and haemostasis
• 影响因子: 6.7
• 作者: Yeung,J;Apopa,PL;Vesci,J;Stolla,M;Rai,G;Simeonov,A;Jadhav,A;Fernandez-Perez,P;Maloney,DJ;Boutaud,O;Holman,TR;Holinstat,M
• 通讯作者: Holinstat,M

Racial Differences Affecting Night Time Blood Pressure Dipping Groups in Hypertensive Patients

影响高血压患者夜间血压下降的种族差异

• DOI: 10.4172/2167-1095.1000214
• 发表时间: 2016
• 期刊: Journal of hypertension : open access
• 作者: Lin Ho Wong;Huang Elaine;R. T. Kong
• 通讯作者: R. T. Kong

Racial differences in resistance to P2Y12 receptor antagonists in type 2 diabetic subjects.

2 型糖尿病受试者对 P2Y12 受体拮抗剂耐药性的种族差异。

• DOI: 10.1124/jpet.114.215616
• 发表时间: 2014
• 期刊: The Journal of pharmacology and experimental therapeutics
• 作者: Cleator,JohnH;Duvernay,MatthewT;Holinstat,Michael;Colowick,NancyE;Hudson,WillieJ;Song,Yanna;Harrell,FrankE;Hamm,HeidiE
• 通讯作者: Hamm,HeidiE

Dichotomous effects of exposure to bivalirudin in patients undergoing percutaneous coronary intervention on protease-activated receptor-mediated platelet activation.

接受经皮冠状动脉介入治疗的患者暴露于比伐卢定对蛋白酶激活受体介导的血小板活化的二分效应。

• DOI: 10.1007/s11239-012-0812-9
• 发表时间: 2013
• 期刊: Journal of thrombosis and thrombolysis
• 影响因子: 4
• 作者: Holinstat,Michael;Colowick,NancyE;Hudson,WillieJ;Blakemore,Dana;Chen,Qingxia;Hamm,HeidiE;Cleator,JohnH
• 通讯作者: Cleator,JohnH