Increased Endothelial Expression of Intercellular Adhesion Molecule-1 in Symptomatic Versus Asymptomatic Human Carotid Atherosclerotic Plaque

Abstract

Background and Purpose-The mechanisms that cause carotid atherosclerotic 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 atheromatous lesions leading to plaque fissuring, endothelial injury, and intraluminal thrombosis. Our goal is to determine whether intercellular adhesion molecule-1 (ICAM-1), a known component of the inflammatory pathway, is preferentially expressed on symptomatic versus asymptomatic carotid plaques. Methods-Carotid plaques from symptomatic (nϭ25) and asymptomatic (nϭ17) patients undergoing carotid endarterectomy with lesions involving Ͼ60% stenosis were snap-frozen at the time of surgery. Immunofluorescence studies were performed to measure the percentage of luminal endothelial surface that expressed ICAM-1. The relationships of stroke risk factors, white blood cell count, percent stenosis, and soluble ICAM-1 (sICAM-1) plasma levels to endothelial ICAM-1 expression were investigated. Results-An increased expression of ICAM-1 was found in the high-grade regions of symptomatic (29.5%Ϯ2.4%, meanϮSEM) versus asymptomatic (15.7%Ϯ2.7%, meanϮSEM) plaques (Pϭ0.002) and in the high-grade versus the low-grade region of symptomatic plaques (29.5Ϯ2.4, meanϮSEM, versus 8.9Ϯ1.6; PϽ0.001). Plasma sICAM-1 levels were not predictive of symptomatic disease, and no significant correlation between risk factor exposure and endothelial ICAM-1 expression was found. Conclusions-An elevation in ICAM-1 expression in symptomatic versus asymptomatic plaque suggests that mediators of inflammation are involved in the conversion of carotid plaque to a symptomatic state. The data also suggest a differential expression of ICAM-1, with a greater expression found in the high-grade region than in the low-grade region of the plaque specimen.

Functional Mineralocorticoid Receptors in Human Vascular Endothelial Cells Regulate Intercellular Adhesion Molecule-1 Expression and Promote Leukocyte Adhesion

“…45,46 In human endarterectomy specimens, EC ICAM1 expression is greater in plaques from symptomatic versus asymptomatic patients, suggesting a role for EC ICAM1 expression in plaque instability. 47 Serum levels of soluble ICAM1 (sICAM1) are elevated in patients at high risk for cardiovascular events and predict cardiovascular outcomes in apparently healthy subjects. 41 In patients with chronic, stable, congestive heart failure, serum aldosterone levels correlate with sICAM1 levels.…”

Stroke Prevention Therapy Beyond Antithrombotics: Unifying Mechanisms in Ischemic Stroke Pathogenesis and Implications for Therapy

“…28 Carotid endarterectomy specimens have shown an elevation of ICAM-1 expression in symptomatic versus asymptomatic plaques and a greater expression of this marker in high-grade versus low-grade regions of the plaque specimens. 29 Activation of matrix-degrading metalloproteinases by activated mast cells (protease secretors) may be an important mechanism in carotid artery and other atherosclerotic plaque destabilization. 30 …”

Primary Prevention of Ischemic Stroke

“…[252][253][254] Monocytes and T cells bind to the expressed adhesion molecules, become activated, and secrete products such as cytokines and proteolytic enzymes that contribute to vessel damage. Markers of inflammation, such as leukocyte adhesion receptors 255 and cytokines, 256 as well as activated T cells and macrophages, 257 are present in carotid endarterectomy specimens of recently symptomatic patients, which suggests that acute inflammatory responses may predispose to plaque destabilization and symptoms. Elevated levels of soluble leukocyte adhesion receptors have been associated with carotid artery atherosclerosis.…”