INCREASED ENDOTHELIAL EXPRESSION OF INTERCELLULAR-ADHESION MOLECULE-1IN SYMPTOMATIC VERSUS ASYMPTOMATIC HUMAN CAROTID ATHEROSCLEROTIC PLAQUE

Background and Purpose-The mechanisms that cause carotid atherosclerot ic plaque to become symptomatic remain unclear. Evidence suggests that mediators of inflammation are not only instrumental in the formation of plaque but may also be involved in the rapid progression of atherom atous lesions leading to plaque fissuring, endothelial injury, and int raluminal thrombosis. Our goal is to determine whether intercellular a dhesion molecule-1 (ICAM-1), a known component of the inflammatory pat hway, is preferentially expressed on symptomatic versus asymptomatic c arotid plaques. Methods-Carotid plaques from symptomatic (n=25) and as ymptomatic (n=17) patients undergoing carotid endarterectomy with lesi ons involving >60% stenosis were snap-frozen at the time of surgery. I mmunofluorescence studies were performed to measure the percentage of luminal endothelial surface that expressed ICAM-1. The relationships o f stroke risk factors, white blood cell count, percent stenosis, and s oluble ICAM-1 (sICAM-1) plasma levels to endothelial ICAM-1 expression were investigated. Results-An increased expression of ICAM-1 was foun d in the high-grade regions of symptomatic (29.5%+/-2.4%, mean+/-SEM) versus asymptomatic (15.7%+/-2.7%, mean+/-SEM) plaques (P=0,002) and i n the high-grade versus the low-grade region of symptomatic plaques (2 9,5+/-2.4, mean+/-SEM, versus 8.9+/-1.6; P<0.001). Plasma sICAM-1 leve ls were not predictive of symptomatic disease, and no significant corr elation between risk factor exposure and endothelial ICAM-1 expression was found. Conclusions-An elevation in ICAM-1 expression in symptomat ic versus asymptomatic plaque suggests that mediators of inflammation are involved in the conversion of carotid plaque to a symptomatic stat e. The data also suggest a differential expression of ICAM-1, with a g reater expression found in the high-grade region than in the low-grade region of the plaque specimen.