Soluble CD40 ligand and atherosclerosis: Linking thrombosis and inflammation

CD40 is a 48-kDa phosphorylated transmembrane glycoprotein with important role in adaptive immunity and inflammation. Platelets express CD40L on activation, which induces proinflammatory changes in endothelial cells via endothelial CD40. Platelets are the major source of soluble CD40L in circulation, and the protean effects of CD40L have led some to suggest that platelet CD40L may be a pivotal link between thrombosis, inflammation and atherosclerosis. The role of CD40L in the immune response involves binding to its receptor on B cells, CD40, to induce B-cell proliferation, generate memory B cells, block B-cell apoptosis, and mediate antibody class switching. Patients with unstable angina pectoris have enhanced plasma concentrations of soluble CD40L. CD40 expression on platelets was significantly higher in patients who had an ischemic stroke compared with patients with asymptomatic carotid stenoses. Post-PCI patients who had restenosis had higher pre-procedural sCD40L levels compared with patients with favourable outcomes. The CAPTURE study has demonstrated the clinical importance of sCD40L in predicting cardiovascular death or nonfatal myocardial infarction during 6 months follow-up. The multiple roles for sCD40 ligand implicate it as a mediator of adverse events among patients with cardiovascular disease.