CD154 and its receptors in inflammatory vascular pathologies.

CD154, a member of the tumor necrosis factor-alpha family, has recently been implicated in the pathophysiology of vascular diseases. Indeed, blockade of CD154 by neutralizing antibodies or genetic disruption in mice prevents atherosclerosis and atherothrombosis. CD154 is believed to interact mainly via the CD40 receptor, however, it has also been found to bind with alphaIIbbeta3 integrin and so induces platelet activation. Moreover, we (and others) have recently identified the integrins alpha5beta1 and Mac-1 as novel CD154 receptors expressed on many cell types. Here, we illustrate the various functional features of these molecules, while describing the increasingly important role of CD40 in CD154-associated vascular pathologies such as atherosclerosis and atherothrombosis.