CD40 Ligand (CD40L), a member of the TNF family, was initially thought to be solely implicated in thymus-dependent humoral responses. However, work by several groups showed that CD40L plays a more global role in various systems. Recent evidence has outlined an important role for CD40L in the physiopathology of the vascular system. Indeed, by interacting with its principal receptor, CD40, or with the recently identified receptors, namely αIIbβ3, α5β1, and Mac-1 integrins, CD40L displayed many biological functions in different types of vascular cells. In addition, the CD40L system was demonstrated a major player in the pathology of vascular diseases, such as atherosclerosis and restenosis. This review outlines the expression pattern and the functional properties of CD40L and its receptors at different cellular levels in the vascular system. In addition, we thoroughly describe evidence showing the implication of CD40L interactions in atherosclerosis, restenosis, and their associated clinical complications.
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