Platelet Acetyl Coenzyme A Carboxylase Phosphorylation in Coronary Artery Disease

In human purified platelets, only thrombin, and not the other platelet agonists, leads to a transient activation of the protein kinase activated by AMP (AMPK) and to phosphorylation of its "bona fide" substrate, ACC on its Ser79. ACC phosphorylation (P-ACC) can be an interesting marker of thrombin action on platelets. Indeed platelet and coagulation interplay, though undoubtedly present in atherosclerosis and atherothrombosis, remains difficult to assess. Our group showed that atherosclerotic mice (SRBI/Apolipoprotein E knock-out) had higher platelet P-ACC compared to corresponding control mice (C57BL6). In agreement with these data, preliminary results showed increased platelet P-ACC in a small cohort of patients admitted for coronary angiogram, with demonstrated coronary artery disease (CAD). In the light of our preliminary results, we sought to analyze platelet P-ACC in a large prospective clinical trial (ACCTHEROMA) in patients admitted for coronary angiogram. The aim of the study is to compare platelet P-ACC in platelets of patients with CAD and more particularly in unstable CAD patients to non-CAD patients. This study could potentially identify patients at high risk of future ischemic cardiovascular events, because of a higher level of thrombin generation.