Inflammation plays a critical role in the initiation, progression, and clinical complications of atherosclerosis.1 Experimental evidence indicates that lesion formation is dependent on heterotypic interactions among immune cells, endothelial cells, and platelets. An emerging paradigm is the linkage between inflammation and thrombosis—namely, inflammation can beget thrombosis, and thrombosis can amplify inflammation. Inflammation itself promotes oxidative stress and endothelial dysfunction, resulting in deficiencies of endogenous antithrombotic factors such as nitric oxide, prostacyclin, and thrombomodulin. Proinflammatory and prothrombotic cellular responses can also be triggered by soluble and cell adhesion signaling molecules. In particular, signaling by the CD40/CD40 ligand (CD40L) system may serve as a pivotal link between inflammation and thrombosis.2 CD40L and CD40 are expressed on endothelial and smooth muscle cells as well as monocytes and have been implicated in various inflammatory responses to vascular injury.3 Binding of CD40L to CD40 on endothelial cells upregulates the expression of inflammatory adhesion molecules (eg, vascular cell adhesion molecule-1 and intercellular adhesion molecule-1), tissue factor, and matrix metalloproteinases,4–6 and it is required for atherosclerotic lesion formation.5 Interestingly, platelets are the most abundant peripheral blood source of CD40L, which binds to glycoprotein IIb/IIIa and promotes thrombosis.7 Indeed, platelets are now considered to be essential for atherosclerotic lesion initiation and lesion growth because of the delivery of platelet-derived proinflammatory factors (eg, RANTES [regulated upon activation, normal T cell expressed, and secreted] and platelet factor-4) to monocytes and the vessel wall.8,9 Article …