Adhesion molecules and atherosclerosis

One early phase of atherosclerosis involves the recruitment of inflammatory cells from the circulation and their transendothelial migration. This process is predominantly mediated by cellular adhesion molecules, which are expressed on the vascular endothelium and on circulating leukocytes in response to several inflammatory stimuli. Selectins (P, E and L) and their ligands (mainly P-selectin ligand) are involved in the rolling and tethering of leukocytes on the vascular wall. Intercellular adhesion molecules (ICAMs) and vascular cell adhesion molecules (VCAM-1), as well as some of the integrins, induce firm adhesion of inflammatory cells at the vascular surface, whereas platelet endothelial cellular adhesion molecules (PECAM-1) are involved in extravasation of cells from the blood compartment into the vessel and underlying tissue. For most of the cellular adhesion molecules, except integrins, soluble forms have been identified in the circulation although their origins are not fully understood. Several lines of evidence support a crucial role of adhesion molecules in the development of atherosclerosis and plaque instability. Expression of VCAM- 1, ICAM- I and L-selectin has been consistently observed in atherosclerotic plaques. There is accumulating evidence from prospective studies for a predictive role of elevated circulating levels of sICAM- I in initially healthy people, and of sVCAM- I in patients at high risk or with overt CAD. A large number of common polymorphisms has been identified in the genes encoding the different adhesion molecules, but studies investigating their relationship either with soluble forms or with CAD are still sparse and often based on small samples. Further research is needed to firmly establish the potential clinical and therapeutic utilities of (soluble) adhesion molecules, but results in both fields hold the promise that in future, adhesion molecules might add information for clinical risk prediction and serve as therapeutic targets. (C) 2003 Elsevier Ireland Ltd. All rights reserved.