Cell Adhesion Molecules in Cardiovascular Disease and Its Risk Factors—What Can Soluble Levels Tell Us?

There are at least three reasons why considerable research energy is currently being directed toward the study of cell adhesion molecules. The blockade of the interaction between leukocytes and the endothelium by agents that mimic or inhibit these adhesion molecules may become a new class of therapeutic agents (1‐3), study of the expression of the molecules on the surface of various cells or of the soluble form in the plasma may provide insights into their role(s) in pathophysiology (4, 5), and levels of soluble cell adhesion molecules in the plasma may be useful tools in stratifying disease severity or prognosis (6, 7). However, these aspects may be inter-related because soluble forms of these adhesion molecules themselves may potentially interfere with leukocyte/endothelial cell interactions, at least in vitro (8, 9). Despite this, soluble adhesion molecules may still be useful in dissecting the pathophysiological events in cardiovascular disease, as it may be presumed that changes in levels may relate to activation or damage to various cells, such as the platelet and endothelium. The selectin family of adhesion molecules has three members. Soluble P-selectin is believed to be the product of activated platelets, although the endothelium displays a membrane-bound form (10, 11). Increased levels are found in a number of conditions, including thrombotic disorders, diabetes, and ischaemic heart disease, and in the latter, raised levels predicted adverse events (12‐14). Although increased levels of soluble E-selectin are the result of cytokine activation of endothelial cells in vitro (15), and raised levels in the plasma have been reported in variant (but not stable) angina (16) and in ischaemic heart disease (17), such raised levels do not seem to predict adverse events cardiovascular events (18) but do predict progression of peripheral atherosclerosis (19). It is still unclear whether or not levels of soluble L-selectin, derived from leukocytes, are altered in cardiovascular diseases although we have been unable to find differences between patients with peripheral atherosclerosis and healthy controls (20). However, Siminiak et al. (21) recently reported raised levels withi n1ht o 3days following admission for acute myocardial infarction, and Haught et al. (22) found low levels in stable and unstable angina, and in acute myocardial infarction.