Bloedplaatjes CD40 co-stimulatie: een sterke leukocyt en endotheel activator in vasculaire inflammatie.

Platelets are critically involved in cardiovascular disease. As a result of atherosclerotic plaque rupture, the exposure of debris instigates arterial thrombosis causing myocardial infarction or stroke. Beyond the hemostatic employment of platelets, recent studies revealed immunological properties of platelets affecting atherosclerosis. We showed that platelet CD40L, an important co-stimulatory molecule, plays a pivotal role in platelet induced inflammation and atherosclerosis progression by stimulating leukocyte activation and recruitment towards the vessel wall. However, the mechanism of platelet interaction with various types of leukocytes and endothelial cells is poorly understood, as is the precise way how this crosstalk accelerates atherosclerosis and atherothrombosis. In a pilot study, we discovered that the competence of platelet CD40, the receptor of CD40L, actually is of higher importance then CD40L itself in promoting atherosclerosis. This proposal therefore aims to unravel the functions and mechanisms of platelet-specific CD40 signaling in vascular inflammation. We plan to study platelet CD40 communication with endothelial cells and different leukocyte subsets in relation to disease. Our ambition is to provide a remarkable novel therapeutic target in cardiovascular medicine acting at the critical interface between inflammation, thrombosis and atherosclerosis.