Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The intercellular adhesion molecule (ICAM) 1 is an Ig-like cell adhesion molecule expressed by several cell types, including leukocytes and endothelial cells. It can be induced in a cell-specific manner by several cytokines, for example, tumor necrosis factor-alpha, interleukin-1, and interferon-gamma, and inhibited by glucocorticoids. Its ligands are the membrane-bound integrin receptors LFA-1 and Mac-1 on leukocytes, CD43, the soluble molecule fibrinogen, the matrix factor hyaluronan, rhinoviruses, and Plasmodium falciparum malaria-infected erythrocytes. ICAM-1 expression is predominantly transcriptionally regulated. The ICAM-1 promoter contains several enhancer elements, among them a novel kappa B element which mediates effects of 12-O-tetradecanoylphorbol-13-acetate, interleukin-1, lipopolysaccharide, tumor necrosis factor-alpha, and glucocorticoids. Expression regulation is cell specific and depends on the availability of cytokine/hormone receptors, signal transduction pathways, transcription factors, and posttranscriptional modification. ICAM-1 plays a role in inflammatory processes and in the T-cell mediated host defense system. It functions as a costimulatory molecule on antigen-presenting cells to activate MHC class II restricted T-cells, and on other cell types in association with MHC class I to activate cytotoxic T-cells. ICAM-1 on endothelium plays an important role in migration of (activated) leukocytes to sites of inflammation. ICAM-1 is shed by the cell and detected in plasma as sICAM-1. Regulation and significance of sICAM-1 are as yet unclear, but sICAM-1 is increased in many pathological conditions. ICAM-1 may play a pathogenetic role in rhinovirus infections. Derangement of ICAM-1 expression probably contributes to the clinical manifestations of a variety of diseases, predominantly by interfering with normal immune function. Among these are malignancies (e.g., melanoma and lymphomas), many inflammatory disorders (e.g., asthma and autoimmune disorders), atherosclerosis, ischemia, certain neurological disorders, and allogeneic organ transplantation. Interference with ICAM-1 leukocyte interaction using mAbs, soluble ICAM-1, antisense ICAM-1 RNA, and in the case of melanoma mAb-coupled immunotoxin, may offer therapeutic possibilities in the future. Integration of knowledge concerning membrane-bound and soluble ICAM-1 into a single functional system is likely to contribute to elucidating the immunoregulatory function of ICAM-1 and its pathophysiological significance in various disease entities.
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PMID:Intercellular adhesion molecule-1. 883 67

It is known that the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) on the surface of vascular endothelial cells is closely related to the formation of early atherosclerotic lesions. In this study, serum soluble ICAM-1(sICAM-1) and soluble VCAM-1(sVCAM-1) were determined by sandwich ELISA both in normal healthy individuals (n = 114) and in patients with hypercholesterolemia (HC, n = 112) or ischemic heart disease (IHD, n = 38) to clarify the significance of the soluble forms of the adhesion molecules in the development of atherosclerotic diseases. IHD patients, not HC patients, showed significant elevation of sICAM-1, but not of sVCAM-1, compared with controls in age and sex-matched subjects. In addition, multiple linear regression analysis showed that sICAM-1 was correlated only to the presence of IHD but not to age and lipids. Multiple logistic regression analysis revealed that sICAM-1 was the most powerful independent predictor of the presence of IHD. On the other hand, sVCAM-1, not sICAM-1, was positively correlated to age. Multiple linear regression analysis showed that age was the most powerful independent predictor of the level of sVCAM-1. These data suggest that sICAM-1 and sVCAM-1 are useful as indices of clinical manifestations of atherosclerosis and aging, respectively.
Atherosclerosis 1997 May
PMID:New indices of ischemic heart disease and aging: studies on the serum levels of soluble intercellular adhesion molecule-1 (ICAM-1) and soluble vascular cell adhesion molecule-1 (VCAM-1) in patients with hypercholesterolemia and ischemic heart disease. 986 51

The aim of this study was to assess the expression of CD11b/CD18 integrin adhesion molecules on the phagocytes of patients with ischaemic diseases, and to evaluate the concentration of soluble adhesion molecules that are released from endothelium (sICAM-1) and from phagocytes (sL-selectin). A total of 370 patients were enrolled: 120 with coronary artery disease (CAD); 50 with peripheral artery occlusive disease (PAOD); and 200 control subjects with no clinical manifestations of ischaemic disease. CD11b/CD18 integrin was detected by flow cytometry, whereas sL-selectin and sICAM-1 concentrations were detected using a sandwich-type immunoassay. CD11b/CD18 integrin expression was found to be higher in the patients with ischaemic disease than in the control subjects (P < 0.001). The PAOD patients had higher values of CD11b/CD18 integrin than the CAD ones (P < 0.01). The concentration of soluble adhesion molecules did not show any significant differences within the three groups (P = NS). The high expression of CD11b/CD18 integrin in ischaemic disease patients may depend on the increased, but probably stable, cytokine network that has been demonstrated to occur in chronic ischaemic diseases: the difference observed between PAOD and CAD patients could be the consequence of higher inflammatory activation probably resulting from the greater extent of the atherosclerotic process in PAOD, or of the more localized ischaemic area in CAD patients. CD11b/CD18 can therefore be considered a marker of chronic phagocyte activation during ischaemic disease. On the other hand, sICAM and sL-selectin concentrations were found to be within the normal range; they have recently been considered as a marker for acute ischaemic events and acute inflammatory process activation. Our results confirm that in uncomplicated atherosclerosis no acute inflammatory process activation should occur.
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PMID:Increased expression of CD11b/CD18 on phagocytes in ischaemic disease: a bridge between inflammation and coagulation. 927 27

Although cellular adhesion molecules (CAMs) are hypothesized to play an important role in atherogenesis, the relationship between CAMs and systemic atherosclerosis is uncertain. Among 92 outpatients (48 men; mean+/-SD age, 65+/-9 years), we evaluated the association of soluble vascular CAM-1 (sVCAM-1) and intercellular adhesion molecule-1 (sICAM-1) with carotid intimal-medial thickness (IMT), an index of early atherosclerosis. All subjects underwent a 2-dimensional ultrasound examination of both carotid arteries at the distal common carotid arteries and bifurcation. sVCAM-1 and sICAM-1 levels measured by enzyme-linked immunosorbent assay were significantly correlated with mean IMT of the common carotid artery (r=0.34 and r=0.30, respectively; P<0.01) and carotid bifurcation (r=0.31 and r=0.26, respectively; P<0.05), whereas sVCAM-1 was also positively associated with maximal carotid IMT (r=0.35, P<0.01). Adjustment for age attenuated the association between sVCAM-1 and common (r=0.16, P=0.13) and bifurcation (r=0.18, P=0.07) carotid IMT but had minimal effect on the associations between sICAM-1 and carotid measurements (r=0.32, P<0.01; r=0.23, P<0.05; for common and bifurcation IMT, respectively). Age-adjusted sICAM-1 levels increased in a stepwise fashion across common carotid IMT tertiles (253+/-27 versus 275+/-24 versus 384+/-26 pg/mL for the lowest, intermediate, and highest IMT tertiles, respectively; P<0.01). A similar trend was also found between sVCAM-1 levels and common carotid IMT tertiles (625+/-60 versus 650+/-53 versus 714+/-58 pg/mL; P<0.15). These associations were minimally affected in analyses adjusting for hypertension, diabetes, smoking, low and high density lipoprotein cholesterol, lipoprotein(a), and homocysteine, or in a subgroup analysis limited to those with no prior history of atherothrombotic disease. These data demonstrate a positive association between serum CAMs with carotid IMT and further support the hypothesis that systemic inflammation may have a role in atherosclerotic lesion development.
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PMID:Circulating cell adhesion molecules are correlated with ultrasound-based assessment of carotid atherosclerosis. 981 16

Cigarette smoking is a risk factor for the development of atherosclerosis. Possible mechanisms for this include leucocytes and platelet activation, and/or damage to the endothelium, any of which may contribute to changes in thrombosis and haemostasis. We examined the acute effects of smoking on these systems by obtaining blood before, immediately after, and at 10 and 30 min after the rapid smoking of two cigarettes in sequence by 20 smokers. Blood samples taken at the same time points from ten non-smokers acted as control material. In the smokers there was a transient rise in leucocyte count and neutrophil activation, but von Willebrand factor (VWF--marking endothelial damage) increased steadily at each time point (P <0.05). There were no changes in neutrophil elastase, soluble intercellular adhesion molecule-1 (sICAM-1 normally increased in smokers), fibrinogen, platelet count or soluble P-selectin (marking platelet activation, also normally increased in smokers). We conclude that the acute smoking of two cigarettes in succession will activate leucocytes and cause endothelial cell damage, but will not immediately influence platelet activity.
Atherosclerosis 1998 Nov
PMID:The influence of acute smoking on leucocytes, platelets and the endothelium. 986 46

The soluble adhesion molecules P-selectin (sP-selectin) and intercellular adhesion molecule-1 (sICAM-1) are derived from platelets and endothelial cells. Circulating concentrations of these soluble adhesion molecules are raised in patients with atherosclerosis and following percutaneous transluminal coronary angioplasty (PTCA). We have investigated the effects of vitamin E supplements (800 IU/day) on circulating plasma ICAM-1 and P-selectin levels pre- and post-PTCA. Patients, randomized to group, were pre-treated with vitamin E or placebo (soybean oil) for 1 month before routine PTCA. Plasma sICAM-1 and sP-selectin were measured by enzyme-linked immunosorbent assay on blood taken immediately pre- and post-PTCA. Total protein and alpha-tocopherol were measured on the same samples. Plasma alpha-tocopherol concentrations increased in patients receiving vitamin E: 19.1 (1.5) [mean (standard error of the mean, SEM)] mg/mL post-PTCA versus 13.9 (0.6) mg/mL pre-PTCA (n=23; P<0.01). Plasma sP-selectin and sICAM-1 levels were not significantly increased following PTCA in the vitamin E group. Pre-angioplasty mean (SEM) plasma sP-selectin concentration in the vitamin E group was 8.83 (0.97) ng/mg protein; the corresponding mean post-angioplasty value was 9.34 (0.89) ng/mg protein (P=0.85). The mean (SEM) pre-angioplasty sICAM-1 concentration in this group was 2.18 (0.24) ng/mg protein, and was 2.20 (0.23) ng/mg protein following angioplasty (P = 0.84). In the placebo group (n = 24) there was a significant increase in mean (SEM) sP-selectin concentration following angioplasty, from 7.48 (0.73) to 9.70 (0.78) ng/mg protein (P<0.05). The change (mean, SEM) in plasma sP-selectin concentration following angioplasty was significantly greater for the placebo group [2.22 (0.50) ng/mg protein] than for the group receiving vitamin E [0.50 (0.50) ng/mg protein] (P<0.02). This difference remained significant (P<0.05) even after adjustment for pre-angioplasty P-selectin concentrations. Mean (SEM) plasma sICAM-1 concentrations remained unchanged following angioplasty [pre-angioplasty: 2.16 (0.20) ng/mg protein; post-angioplasty: 1.97 (0.13) ng/mg protein]. Vitamin E may therefore limit platelet or endothelial activation during PTCA.
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PMID:Effect of vitamin E supplementation on circulating cell adhesion molecules pre- and post-coronary angioplasty. 1102 17

Cholesterol lowering involving different therapies improves the clinical outcome of patients. To define the underlying pathomechanism, we studied whether treatment with statins was associated with changes in blood thrombogenicity, endothelial dysfunction and soluble adhesion molecule levels. Fifty hypercholesterolemic patients were treated with pravastatin (40 mg/day, n=24) or simvastatin (20 mg/day, n=26). Lipid profile and blood thrombogenicity were assessed in all patients before and after 3 months of cholesterol reducing therapy. Blood thrombogenicity was assessed as thrombus formation, perfusing non-anticoagulated blood directly from the patients' vein through the Badimon perfusion chamber (shear rate 1690/s). Endothelial-dependent vasomotor response was tested by laser-Doppler flowmeter. Soluble adhesion molecule level were measured by ELISA. Total and LDL cholesterol were reduced in the two treatment groups by statin therapy. Statin therapy was associated with a significant reduction in blood thrombogenicity and endothelium-dependent vasoresponse. No differences were observed between simvastatin or pravastatin treatment. Lipid lowering by statins had no effect on plasma levels of fibrinogen, sL-selectin, sP-selectin and sICAM-1 antigen. Cholesterol lowering by both statins reduced the increased blood reactivity and endothelial dysfunction present under hypercholesterolemia. The multiple effects of lipid lowering therapy by statins may explain the benefits observed in recent epidemiological trials.
Atherosclerosis 2000 Nov
PMID:Statins and cardiovascular diseases: the multiple effects of lipid-lowering therapy by statins. 1105 14

The genetic predisposition for cardiovascular disease seems to play an important role in atherogenesis. Atherosclerosis, which can be clinically asymptomatic for many years, begins early in life. Therefore finding markers of early atherosclerotic process would be of great importance for screening and early treatment of these children. As the result of endothelial dysfunction, the adhesion molecules (VCAM-1, ICAM-1, ELAM) are overexpressed. These molecules are shed from the surface and can be measured, as soluble forms in serum. Therefore they can be regarded as early markers of atherosclerosis. The aim of the study was to measure the serum levels of soluble adhesion molecules ELAM, ICAM-1, VCAM-1 and plasma lipid profile--total (TC), LDL (LDL-C) and HDL-cholesterol (HDL-C) and triglycerides (TG) in children from families of high risk for cardiovascular diseases. Forty-eight children were studied, 24 children from high risk families, according to NCEP definition: one or two parents had clinical manifestation of cardiovascular disease before the age of 65 years (mother) or 55 years (father). Twenty-four healthy children without familial history of cardiovascular disease were used as the control. Children of either group did not have any metabolic diseases. The concentration of sELAM, sICAM-1 and sVCAM-1 were assessed using ELISA kits. Soluble ICAM-1 level was significantly higher in high risk group in comparison to control (p<0.02). The soluble VCAM-1 and ELAM levels did not differ significantly between the groups. There were no changes in total cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides between the groups. In normolipidemic children from families with high risk for atherosclerosis the soluble ICAM-1 levels are significantly higher as compared to control.
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PMID:Soluble ICAM-1, VCAM-1 and E-selectin in children from families with high risk of atherosclerosis. 1117 23

This study was performed to determine whether the levels of soluble intercellular adhesion molecule-1 (sICAM-l) and soluble endothelial molecule-1 (sE-selectin) were elevated in subjects with hypercholesterolemia who presented with no other risk factors or evidence of atherosclerosis. The effects of administration of an HMG-CoA reductase inhibitor on the serum levels of these molecules were also examined. Forty hypercholesterolemic subjects (HCh) (19 males and 21 females), without hypertension or cardiovascular disease, received placebo for 4 weeks. The patients were then randomized in two groups; 20 of them (simvastatin group) were treated with simvastatin (20 mg/day) and the other 20 (placebo group) continued placebo administration. After 12 and 24 weeks of either simvastatin or placebo treatment, sICAM-1 and sE-selectin levels were measured. The same parameters were measured in 20 control subjects (C) with normal cholesterol levels, matched for sex and age. HCh had sICAM-1 basal values higher than C (352.4+/-57.9 ng/ml versus 114.9+/-89.6 ng/ml; P<0.001); however, sE-selectin basal values were not different in the two groups. No correlation was observed between HCh sICAM-1 levels and cholesterol levels (total and low-density lipoprotein). Furthermore, cholesterol-lowering treatment with simvastatin did not significantly diminish sICAM-1 levels. Our findings would support the hypothesis that patients with isolated hypercholesterolemia and without clinical atherosclerosis may be silent carriers of arterial subendothelial inflammation, expressed as an increase of sICAM-1.
Atherosclerosis 2001 Mar
PMID:Effects of simvastatin treatment on sICAM-1 and sE-selectin levels in hypercholesterolemic subjects. 1122 35

Inflammation plays an important role in the development of atherosclerosis, but the specific stimuli governing cytokine release in atherogenesis are unknown. We examined the hypothesis that hypertension may increase the risk of atherosclerosis via proinflammatory effects. In a cross-sectional study involving 508 apparently healthy men, we studied the association between blood pressure and baseline plasma concentrations of 2 inflammatory markers, intercellular adhesion molecule-1 (sICAM-1) and interleukin-6 (IL-6). Increase in systolic blood pressure (SBP) (P=0.003), pulse pressure (PP) (P=0.019), and mean arterial pressure (P=0.014) was significantly associated with levels of sICAM-1. All of these measures of blood pressure, as well as diastolic blood pressure (DBP), were significantly associated with levels of IL-6 (all, P</=0.001). In multiple linear regression models controlled for age and other cardiac risk factors, SBP (7.6 ng/mL per 10 mm Hg, P=0.016) and PP (8.13 ng/mL per 10 mm Hg, P=0.038) were significantly associated with sICAM-1 levels, whereas SBP (0.11 pg/mL per 10 mm Hg, P<0.001), DBP (0.11 pg/mL per 10 mm Hg, P=0.008), PP (0.10 pg/mL per 10 mm Hg, P=0.009), and mean arterial pressure (0.15 pg/mL per 10 mm Hg, P<0.001) had similar strong relationships with log-transformed IL-6 levels. Therefore, in apparently healthy men, we observed significant graded relationships between blood pressure and levels of sICAM-1 as well as IL-6. These data suggest that increased blood pressure may be a stimulus for inflammation and that this is a possible mechanism underlying the well-established role of hypertension as a risk factor for atherosclerotic disease.
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PMID:Blood pressure and inflammation in apparently healthy men. 1156 12


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