Increasing evidence shows that the cells associated with atherogenesis (platelets, endothelial
and smooth muscle cells, fibroblasts, monocytes, macrophages and T lymphocytes) express proinflammatory
pathways of CD40 signalling. Activation of platelets CD40/CD40L system and
its counterpart CD40 receptors on vascular cell surface induces the expression of various
adhesion molecules, cytokines, chemokines, growth factors, matrix metalloproteinases and
reactive oxygen species, the substances which are responsible for plaque formation,
destabilisation and rupture. Disturbed laminar blood flow (low wall shear stress) can mediate
CD40/CD40L system signalling by increasing the residence time of the interaction between
platelets and endothelium.
Experimental studies provide considerable data indicating that interruption of CD40 signalling
significantly inhibits the progression of established atheroma and altered plaque composition
for a lipid-poor collagen-rich stable plaque phenotype. Recent data suggest different aspects
of CD40/CD40L system activation in the context of risk factors (hypercholesterolaemia, diabetes
mellitus, obesity and cigarette smoking) link them into the pro-inflammatory and prothrombotic
milieu, aggravating the atherosclerotic process. Activation of the CD40/CD40L
system plays a pivotal role in acute coronary syndromes as well as acute cerebral ischaemia.
After percutaneous coronary intervention the risk of restenosis increases with high levels of
plasma-soluble CD40L (sCD40L). In apparently healthy women sCD40L concentration has
been recognised as an independent risk factor of the first acute coronary event. Clopidogrel,
aspirin, statins and some oral hypoglycaemic agents share common anti-inflammatory properties
including inhibition of CD40/CD40L intercellular signalling. To prevent plaque progression,
destabilisation and thrombotic complications, anti-platelet treatment strategy should be
focused on inhibition of platelet activation instead of on response to platelet aggregation