Inflammation, cell adhesion molecules, and stroke: tools in pathophysiology and epidemiology?

Since their development approximately a decade ago, cell adhesion molecules have been attracting interest for a number of reasons. For example, the blockade of the interaction between leukocytes and the endothelium by agents that mimic or inhibit these adhesion molecules may provide the basis for a new class of therapeutic agents, although promising studies in animals1–3 have yet to be translated into products proven to be effective in humans. 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 in cardiovascular, connective tissue and neoplastic diseases,4,5 and differences in 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 related, as soluble forms themselves may interfere with leukocyte/endothelial cell interactions, at least in vitro.8,9 Despite this, soluble adhesion molecules may 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 two principal 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 ischemic heart disease,12,13 and raised levels predict adverse events,14 even in apparently healthy individuals.15 Although increased levels of soluble E-selectin are the result of cytokine activation of endothelial cells in vitro,16 and raised levels in the plasma have been reported in variant (but not stable) angina17 and in ischemic heart disease,18 such raised levels seem unable to predict adverse cardiovascular events19 but do predict restenosis following percutaneous angioplasty in the peripheral arteries.20 See article on page 2182