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利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 这项研究的目的是验证这样一种假设，即通过氯吡格雷抑制II型糖尿病患者的血小板二磷酸腺苷P2Y12受体，将导致血小板活化和血管炎症减少，并增加血管内皮细胞一氧化氮的可获得性。 该项目的具体目标是：在基线和服用氯吡格雷一个月后，对没有动脉粥样硬化临床表现的II型糖尿病患者进行以下测量： 1)通过血管炎症的血清标记物进行血管炎症， 2)通过测定肱动脉、内皮依赖性血流介导的血管扩张来获得内皮一氧化氮，以及 3)通过检测活化的可溶性CD40配体的血清标志物，以及测定血小板的收缩力、凝块弹性系数和凝血酶生成时间来激活血小板。 目前，除了有外周动脉疾病的患者外，没有记录的急性缺血事件的患者不建议使用氯吡格雷。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获得性。 动脉粥样硬化导致冠状动脉疾病是西方人死亡的主要原因。以前被认为是一种主要涉及动脉壁脂积聚的疾病，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。引发炎症的一个或多个原因正在调查中，但感染、创伤或生理紊乱已被推测。最近，血小板活化和聚集被认为是动脉粥样硬化中血管炎症过程的可能机制。

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.