Soluble adhesion molecules and the search for biomarkers for atherosclerosis.

Advances in the understanding of the molecular basis of inflammation, atherogenesis, and plaque instability have led to the identification of a number of molecules that are posited to play a critical role in various aspects of atherosclerotic lesions and/or their lability, which can be measured quantitatively in plasma. Intercellular cell adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) are two important members of the immunoglobulin gene superfamily that play important but different roles in the adhesion of leukocytes to the vascular endothelium. VCAM-1, which is the endothelial ligand for 4 1 (very late antigen 4 [VLA-4]), has been postulated to play the more critical role in monocyte adherence to endothelial cells under flow conditions. ICAM-1 ligands include CD11a/CD18 (LFA-1) and CD11b/ CD18 (Mac-1), which are present on monocytes, lymphocytes, and neutrophils. Increased expression of ICAM-1 and VCAM-1 is observed in atherosclerotic lesions, and mice deficient in either ICAM-1 or VCAM-1 have reduced response to experimental atherosclerotic stimuli (eg, apolipoprotein E deletion). In the mouse, a deficiency of VCAM-1 seems to play a more important role in the initiation of atherosclerosis than does a deficiency of ICAM-1.1 Although membrane-bound forms of either adhesion molecule are difficult to measure in vivo, soluble forms can be detected in the serum or plasma and are increased in many conditions with an inflammatory component.2 The levels of soluble ICAM-1 (sICAM-1) in apolipoprotein E–deficient mice increases over time in parallel with the progression of atherosclerosis, providing evidence in a murine model that sICAM-1 may correlate with the burden of atherosclerosis.3