Adhesion molecule expression in symptomatic and asymptomatic carotid stenosis (original) (raw)
Related papers
Stroke, 1998
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. (Stroke. 1998;29:1405-1410.)
Circulating adhesion molecules are correlated with ultrasonic assessment of carotid plaques
Clinical Science, 2003
The relationship between levels of circulating intercellular cell-adhesion molecule-1 (cICAM-1) or P-selectin (cP-selectin) and the severity of carotid atherosclerosis was examined in 301 outpatients undergoing duplex ultrasonographic examination. Carotid plaque was defined as an intima-media thickness greater than 1.0 mm, and a plaque score (PS) was calculated from the plaque thickness in both carotid arteries. Multivariate analysis demonstrated significant positive associations between cICAM-1 and the number of plaques [beta = 0.11; confidence interval (CI), 0.007-0.213], maximum intima-media thickness (beta = 0.11; CI, 0.01-0.219), and PS (beta = 0.10; CI, 0.001-0.205). In contrast, no significant association was found for cP-selectin. cP-selectin did not increase until atherosclerosis was advanced (PS > 10), showing a marked increase in patients with >/= 50% stenosis. The circulating levels of both proteins are related to real measurements of plaque formation in the carotid arteries independently of classical risk factors. Marked elevation of cP-selectin occurs in advanced carotid atherosclerosis after gradual elevation of cICAM-1.
Journal of Vascular Surgery, 2018
Background-Molecular imaging of carotid plaque vulnerability to atheroembolic events is likely to lead to improvements in patient selection for carotid endarterectomy (CEA). The aims of this study were to assess the relative value of endothelial inflammatory markers for this application and develop molecular ultrasound contrast agents for their imaging. Methods-Human CEA specimens were obtained prospectively from asymptomatic (30) and symptomatic (30) patients. Plaques were assessed by semi-quantitative immunohistochemistry (IHC) for vascular cell adhesion molecule-1 (VCAM-1), lectin-like oxidized LDL receptor-1 (LOX-1), P-selectin and von Willebrand Factor (vWF). Established small peptide ligands to each of these targets were then synthesized and covalently conjugated to the surface of lipid-shelled microbubble ultrasound contrast agents, which were then evaluated in a flow chamber for binding kinetics to activated human aortic endothelial cells (HAECs) under variable shear conditions.
The distribution of adhesion molecules in human atherosclerosis
Histopathology, 1993
Chronic inflammatory cells are a recognized component of atherosclerotic plaques at all stages of development. As adhesion molecules play a fundamental role in inflammatory processes, we have carried out an immunohistochemical investigation of the distribution of endothelial leucocyte adhesion molecule-1 (ELAM-1)*, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in human atherosclerotic lesions. Autopsy specimens from abdominal aorta and coronary arteries were obtained from 21 cases within 24 h of death. ELAM-1 and ICAM-1 were consistently expressed by the entire intimal endothelium of normal coronary arteries and also by the intimal endothelium overlying aortic fatty streaks. Both coronary artery and aortic lesions showed strong staining for ICAM-1 on and around macrophages. VCAM-1 was not detected on intimal endothelial cells, but strong staining of adventitial lymphoid aggregates for this molecule was seen. This work suggests a role for ELAM-1 and ICAM-1 in mononuclear cell recruitment during atherogenesis.
Inflammatory Mediators and Cell Adhesion Molecules as Indicators of Severity of Atherosclerosis
Arteriosclerosis, Thrombosis, and Vascular Biology, 2002
Inflammatory mediators and soluble cell adhesion molecules predict cardiovascular events. It is not clear whether they reflect the severity of underlying atherosclerotic disease. Within the Rotterdam Study, we investigated the associations of C-reactive protein (CRP), interleukin-6 (IL-6), soluble intercellular adhesion molecule-1, and soluble vascular cell adhesion molecule-1 with noninvasive measures of atherosclerosis. Levels of CRP were assessed in a random sample of 1317 participants, and levels of IL-6 and soluble cell adhesion molecules were assessed in a subsample of 714 participants. In multivariate analyses, logarithmically transformed CRP (regression coefficient []ϭϪ0.023, 95% CI Ϫ0.033 to Ϫ0.012) and IL-6 (ϭϪ0.025, 95% CI Ϫ0.049 to Ϫ0.001) were inversely associated with the ankle-arm index. Only CRP was associated with carotid intima-media thickness (ϭ0.018, 95% CI 0.010 to 0.027). Compared with the lowest tertile, the odds ratio for moderate to severe carotid plaques associated with levels of CRP in the highest tertile was 2.0 (95% CI 1.3 to 3.0). Soluble intercellular adhesion molecule-1 levels were strongly associated with carotid plaques (odds ratio 2.5, 95% CI 1.5 to 4.4 [highest versus lowest tertile]). Soluble vascular cell adhesion molecule-1 was not significantly associated with any of the measures of atherosclerosis. This study indicates that CRP is associated with the severity of atherosclerosis measured at various sites. Associations of the other markers with atherosclerosis were less consistent.
Atherosclerosis, 2002
Since inflammatory mechanisms seem to be involved in different stages of atherosclerosis, we analysed a random populationbased sample of 972 subjects to assess the relationships between soluble intercellular adhesion molecule-1 (sICAM-1), subclinical peripheral atherosclerosis and intima-media thickness (IMT). B-mode ultrasonography was used to assess the presence of carotid (common and internal) and femoral atherosclerotic plaques and to measure common carotid IMT (avoiding plaque sites). Mean sICAM-1 level was 287.4 (standard deviation: 102.8) and 255.2 (83.5) ng/ml, respectively, in subjects with and without carotid plaques (P B/0.0001). It equalled 286.7 (101.1) and 249.7 (79.7) ng/ml, respectively, in subjects with and without femoral plaques (P B/0.0001). Subjects beyond the 90th percentile of common carotid IMT had higher sICAM-1 levels than those below, but this was not significant (P0/0.08). Multiple logistic regression analyses adjusted for age, gender and other cardiovascular risk factors showed that sICAM-1 was independently associated with the risk of having at least one carotid plaque (adjusted odds ratio for a 10 ng/ml increase in sICAM-1: OR0/1.03, 95% confidence interval: [1.02 Á/1.05]) and with the risk of having at least one femoral plaque (adjusted OR0/1.04 [1.02 Á/1.06]). On the other hand, no significant relationship was found in multivariate analysis between sICAM-1 and common carotid IMT.
Cerebrovascular Diseases Extra, 2018
Background: Echolucent carotid plaques have been related to an increased risk of ischemic cerebrovascular events. The aim of the present study was to evaluate whether a new objective ultrasonographic parameter, the statistical geometric feature (SGF), reflecting spottiness of carotid plaques, can be associated with cerebrovascular symptoms and with a rupture-prone plaque phenotype. Methods: The plaques of 144 patients who underwent carotid endarterectomy were included in this study. SGF and plaque area were estimated by outlining the plaque on ultrasound (US) images. The correlation coefficient for inter-and intraobserver variability was 0.69 and 0.93, respectively. The SGF values were normalized to the degree of stenosis (SGF/DS). The plaques collected at surgery 1 day after the US were analyzed histologically, and inflammatory markers and matrix metalloproteinases (MMPs) were measured. Results: Patients with ipsilateral hemispheric symptoms had higher SGF/DS compared to patients without symptoms (0.82 [0.59-1.16] vs. 0.70 [0.56-0.89], p = 0.01). Analysis of plaque components revealed a positive correlation between SGF/DS and the percentage of the plaque area stained for lipids, macrophages, and hemorrhage. A correlation was also found between SGF/DS and plaque expression of interleukin-6, monocyte chemoattractant protein-1, macrophage inflammatory protein-1β, vascular endothelial growth factor A, CC motif chemokine 3 and 20, and MMP-9. An inverse correlation was found with plaque levels of osteoprotegerin. Conclusions: The present study supports the concept that spottiness is a feature of the carotid plaques rich in inflammation and can be associated with the typical phenotype of high-risk plaques.