PILOT STUDY TO DETERMINE THE EFFECT OF ANTIPLATELET THERAPY WITH CLOPIDOGREL

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 本研究的目的是验证通过氯吡格雷抑制II型糖尿病患者血小板二磷酸腺苷P2 Y12受体将导致血小板活化和血管炎症减少以及血管内皮一氧化氮可用性增强的假设。 本项目的具体目的是：在基线和氯吡格雷给药1个月后，测量无动脉粥样硬化临床表现的II型糖尿病患者的以下指标： 第一章 通过血管炎症的血清标志物， （二） 通过测定肱动脉、内皮依赖性血流介导的血管舒张和 第三章 通过测量活化可溶性CD 40配体的血清标志物和测量血小板收缩力、凝块弹性模量和凝血酶生成时间来测量血小板活化。 目前，氯吡格雷长期给药不适用于没有记录的急性缺血事件的患者，但外周动脉疾病患者除外。上述目的将允许确定在目前的糖尿病治疗中加入氯吡格雷是否会提供额外的抗炎活性并改善内皮一氧化氮的可用性。 导致冠状动脉疾病的动脉粥样硬化是西方世界的主要死亡原因。 以前认为是一种主要涉及动脉壁脂质积聚的疾病，现在认为血管炎症是导致内皮功能障碍和脂肪条纹形成的关键组成部分，这是动脉粥样硬化形成的初始事件。 引发炎症的原因正在调查中，但已假定感染，创伤或生理紊乱。 最近，血小板活化和聚集被认为是动脉粥样硬化血管炎症过程的机制。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The aim of this study is to test the hypothesis that inhibiting the platelet adenosine diphosphate P2Y12 receptor in patients with type II diabetes via clopidogrel, will result in a reduction in platelet activation and vascular inflammation, and enhanced vascular endothelial nitric oxide availability. The specific aims of this project are: To measure the following, at baseline and after one month of clopidogrel administration, in patients with type II diabetes without clinical manifestations of atherosclerosis: 1) Vascular inflammation via serum markers of vascular inflammation, 2) Endothelial nitric oxide availability by determining brachial artery, endothelial-dependent flow-mediated vasodilation, and 3) Platelet activation by measuring the serum marker of activation soluble CD40 ligand and measuring platelet contractile force, clot elastic modulus, and thrombin generation time. Currently, chronic clopidogrel administration is not indicated in patients without a documented acute ischemic event except in patients with peripheral arterial disease. The aims above will allow determination if the addition of clopidogrel to current diabetic therapy will provide additional anti-inflammatory activity and improve endothelial nitric oxide availability. Atherosclerosis leading to coronary artery disease is the leading cause of death in the westernized world. Previously thought to be a disease primarily involving lipid accumulation in arterial walls, it is now thought that vascular inflammation is a crucial component leading to endothelial dysfunction and fatty streak formation, the initial events in atherogenesis. The cause or causes for the initiation of inflammation are under investigation, but infection, trauma or disordered physiology have been postulated. Most recently platelet activation and aggregation have been proposed as mechanisms, which may contribute to the vascular inflammatory process in atherosclerosis.