The induction of cellular interactions in atherogenesis and their modulation.

Interactions between vascular cells and blood cells are central to the development of the atherosclerotic process. Under normal circumstances, blood cells do not associate with the blood vessel; however, in response to atherogenic stimuli, platelets, lymphocytes and mononuclear leukocytes interact with the vessel wall and induce changes in the vascular micro-environment that support atheroma formation. These changes include the enhancement of endothelial permeability, the conversion of the normal endothelium from an anti-thrombotic to a pro-thrombotic phenotype, the induction of endothelial and vascular-smooth-muscle migration, the stimulation of vascular-smooth-muscle-cell replication, and the elaboration of extracellular matrix by the vascular-smooth-muscle cell [ 13. The principal effectors that mediate this dramatic modification of vascular properties are soluble intercellular-signalling molecules that are known as cytokines.