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.
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