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)

Comparative analysis of cytokines and sCAM secretion within the lymphocyte chromatin state are possible evidence of inflammatory reactions in atherosclerosis. Two types of response were studied: coagulation and fibrinolysis (incubation of blood clot within 6 hours at 37 degrees C) and standardized viscosimetric flow using a rotational viscometer (shear rate 100 l/s, 60 seconds at 37 degrees C, and incubation within 6 hours at 37 degrees C). Cytokines IL-1alpha, IL-1beta, IL-6, IL-8, IL-10 (Immunotech, France), endothelin-1, and soluble cell adhesion molecules (sCAM) sP- and sE-selectin, sICAM-1, and sVCAM-1 (R&D, UK) have been determined using ELISA kits (photometer, Biomek-1000, Beckman, USA). The chromatin of lymphocyte nuclei was studied using the computer TV morphodensitometry system DiaMorph (Russia) and smears dyed specifically for DNA. Correlational changes in morphodensitometric (MDM) parameters and cytokine and sCAM levels in two tests were compared to initial levels. After rheologic testing, lymphocyte nuclei as a whole had not changed, but chromatin activity had decreased. Reorganization of nuclei after the coagulation test was observed. Endothelin-1 and sP- and sE-selectin levels were not related to function of lymphocytes (by MDM data) as seen in both tests; it is probable that another cell-cell communication mechanism had been switched on. We established a strong correlation between chromatin activity of lymphocytes and the serum concentration of IL-1beta, IL-6, and IL-10, which are the active participants in the pro- and anti-inflammatory program in atherogenesis. Results are evidence of the role of lymphocytes in pro- and anti-inflammatory cytokine reactions and cytokine-like sCAM activity in atherosclerosis.
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PMID:Chromatin image analysis provides new evidence of the relation of lymphocytes to cytokines and sCAM in the inflammatory nature of atherosclerosis. 1179 95

Epidemiological studies have implicated periodontal disease (PD) as a risk factor for the development of cardiovascular disease (CVD). These studies addressed the premise that local infection may perturb the levels of systemic inflammatory mediators, thereby promoting mechanisms of atherosclerosis. Levels of inflammatory mediators in the sera of subjects with only PD, only CVD, both diseases, or neither condition were compared. Subjects were assessed for levels of C-reactive protein (CRP), serum amyloid A (SAA), ceruloplasmin, alpha(1)-acid-glycoprotein (AAG), alpha(1)-antichymotrypsin (ACT), and the soluble cellular adhesion molecules sICAM-1 and sVCAM by enzyme-linked immunoabsorbent and/or radial immunodiffusion assays. CRP levels in subjects with either condition alone were elevated twofold above subjects with neither disease, whereas a threefold increase was noted in subjects with both diseases (P = 0.0389). Statistically significant increases in SAA and ACT were noted in subjects with both conditions compared to those with one or neither condition (P = 0.0162 and 0.0408, respectively). Ceruloplasmin levels were increased in subjects with only CVD (P = 0.0001). Increases in sVCAM levels were noted in all subjects with CVD (P = 0.0054). No differences in sICAM levels were noted among subject groups. A trend toward higher levels of AAG was noted in subjects with both conditions and for ACT in subjects with only PD. Immunohistochemical examination of endarterectomy specimens of carotid arteries from subjects with atherosclerosis documented SAA and CRP deposition in association with atheromatous lesions. The data support the hypothesis that localized persistent infection may influence systemic levels of inflammatory mediators. Changes in inflammatory mediator levels potentially impact inflammation-associated atherosclerotic processes.
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PMID:Systemic inflammation in cardiovascular and periodontal disease: comparative study. 1187 89

To study the association of plasma concentrations of soluble adhesion molecules (sICAM-1, sVCAM-1 and sE-selectin) with atheroslerotic lesions at the origin of the internal carotid artery (ICA). 179 subjects were investigated by color Doppler ultrasound of whom 133 had and 46 had no plaques at the ICA origin. Stepwise logistic regression analysis revealed that hypertension (p < 0.001), sICAM-1 concentrations (p < 0.01) and smoking (p < 0.05) were independently associated with the presence of ICA plaques. Multivariate regression analysis revealed that sICAM-1 concentrations in subjects with plaque were negatively associated with the degree of ICA stenosis (p < 0.01) and positively associated with previous cerebral ischemia (p < 0.01), coronary heart disease (p < 0.05) and peripheral artery disease (p < 0.05). In conclusion, elevated sICAM-1 concentrations are independently associated with atherosclerosis of the ICA origin and are predominantly increased in patients with low-grade lesions and with clinical manifestations of vascular disorders.
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PMID:Circulating adhesion molecules in patients with internal carotid artery stenosis. 1209 45

Cell adhesion molecules play a rather important role in the development of atherosclerosis mediating the attachment of monocytes to the endothelium. It has also been well established that hyperlipidemia is a risk factor for atherosclerosis from childhood. The aim of this study was to investigate whether the soluble adhesion molecules correlate with the circulating lipid levels in children. The study population consisted of 107 children (64 boys, 43 girls) aged 6-13 y. Parental history of cardiovascular disease, age, gender, and anthropometric parameters were recorded in all children. Blood samples were obtained from every child following a 12-hour fasting period. Serum triglycerides, total cholesterol, and its fractions as well as plasma levels of P and E selectins and adhesion molecules sVCAM-1 and sICAM-1 were determined. After controlling for age and body mass index, both sVCAM-1 and sP-selectin levels were inversely associated with HDL values (r = -0.33, p = 0.005 and r = -0.39, p = 0.001, respectively). A significant positive correlation was found between sVCAM-1 and triglycerides (r = 0.48, p < 0.001). An increment of 10 mg/dL of HDL corresponds to about 50% reduction of the odds for endothelial dysfunction whereas an increment of 10 mg/dL of triglyceride levels indicates a more than 3-fold excess risk, using either sP-selectin or sVCAM-1 levels as a surrogate for the determination of endothelial dysfunction. We suggest that HDL-C and triglycerides correlate in a biologically plausible way with soluble adhesion molecules, which therefore could be considered as useful indicators of the process of preclinical atherosclerosis even from childhood.
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PMID:The impact of serum lipid levels on circulating soluble adhesion molecules in childhood. 1219 84

This randomised double-blind, placebo-controlled, clinical trial investigated the effect of 3 months of treatment with calcium dobesilate on endothelium-dependent vasodilation, markers of endothelial function, blood pressure, and markers of oxidation in obese, male smokers. Vascular effects may depend on the type of vessel and we, therefore, investigated both smaller arteries, i.e. resistance arteries and small arterioles, and large conduit arteries. Vascular function was measured by acetylcholine- and sodium-nitroprusside-mediated vasodilation, and capillary recruitment, in the skin microcirculation; by forearm blood flow (FBF) responses to several agonists and to N-G-monomethyl L-arginine (L-NMMA) in the forearm vascular bed; by flow-mediated vasodilation in the brachial artery; and by determination of soluble levels of vascular cell adhesion molecule-1 (sVCAM-1), intercellular adhesion molecule-1 (sICAM-1) and E-selectin. Twenty-eight individuals received dobesilate and 24 placebo. No effect of calcium dobesilate on endothelial function, blood pressure or markers of oxidation was observed compared with placebo. The difference in acetylcholine-mediated vasodilation in the microcirculation was -52.1%-point (95% confidence interval -132.8 to 28.1); in sodium-nitroprusside-mediated vasodilation in the microcirculation, 2.6%-point (-95.1 to 100.2); in capillary recruitment, 2.5%-point (-6.8 to 11.7); in acetylcholine-induced increases in FBF (n=28), 23%-point (-173 to 126); in L-NMMA-induced reduction of basal FBF, -2.8%-point (-29.3 to 23.8); in flow-mediated vasodilation of the brachial artery, 0.3%-points (-2.7 to 3.3); in 24-h systolic blood pressure, 2.1 mmHg (-1.3 to 5.5); in soluble VCAM-1, 54 ng/ml (-8 to 115); in soluble ICAM-1, 9 ng/ml (-49 to 67); in sE-selectin, -17 ng/ml (-44 to 11); in ketocholesterol 5 nM (-17 to 26); and in oxidised LDL -1.6 U/l (-6.7 to 3.5). We have shown that endothelial function, blood pressure, and markers of oxidation were not affected by 3 months of treatment with calcium dobesilate in mildly obese, smoking men. Thus, our data provide no evidence of an effect on vascular function of calcium dobesilate in humans.
Atherosclerosis 2003 Sep
PMID:The effect of calcium dobesilate on vascular endothelial function, blood pressure, and markers of oxidation in obese male smokers: a placebo-controlled randomised clinical trial. 1295 83

One early phase of atherosclerosis involves the recruitment of inflammatory cells from the circulation and their transendothelial migration. This process is predominantly mediated by cellular adhesion molecules, which are expressed on the vascular endothelium and on circulating leukocytes in response to several inflammatory stimuli. Selectins (P, E and L) and their ligands (mainly P-selectin ligand) are involved in the rolling and tethering of leukocytes on the vascular wall. Intercellular adhesion molecules (ICAMs) and vascular cell adhesion molecules (VCAM-1), as well as some of the integrins, induce firm adhesion of inflammatory cells at the vascular surface, whereas platelet endothelial cellular adhesion molecules (PECAM-1) are involved in extravasation of cells from the blood compartment into the vessel and underlying tissue. For most of the cellular adhesion molecules, except integrins, soluble forms have been identified in the circulation although their origins are not fully understood. Several lines of evidence support a crucial role of adhesion molecules in the development of atherosclerosis and plaque instability. Expression of VCAM-1, ICAM-1 and L-selectin has been consistently observed in atherosclerotic plaques. There is accumulating evidence from prospective studies for a predictive role of elevated circulating levels of sICAM-1 in initially healthy people, and of sVCAM-1 in patients at high risk or with overt CAD. A large number of common polymorphisms has been identified in the genes encoding the different adhesion molecules, but studies investigating their relationship either with soluble forms or with CAD are still sparse and often based on small samples. Further research is needed to firmly establish the potential clinical and therapeutic utilities of (soluble) adhesion molecules, but results in both fields hold the promise that in future, adhesion molecules might add information for clinical risk prediction and serve as therapeutic targets.
Atherosclerosis 2003 Oct
PMID:Adhesion molecules and atherosclerosis. 1461 98

Purpose of this study was to investigate the effect of combined administration of antioxidant vitamins C and E on endothelial function and serum levels of inflammatory markers such as tumor necrosis factor alpha (TNF-alpha), interleukines 1b (IL-1b) and 6 (IL-6), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and E-selectin in chronic smokers. Forty-three smokers were randomly divided into four groups receiving vitamin C 2 g/day (group A), vitamin C 2 g/day plus vitamin E 400 IU/day (group B), vitamin C 2 g/day plus vitamin E 800 IU/day (group C) or no antioxidant treatment (group D), for 4 weeks. Forearm blood flow (FBF) was measured using venous occlusion strain gauge plethysmography. Forearm vasodilatory response to reactive hyperemia (RH%) was expressed as the percentage change from baseline to post reactive hyperemia blood flow. RH% was significantly increased in groups B (P<0.05) and C (P<0.01), but remained unaffected in groups A and D. Serum levels of IL-1b, IL-6, sVCAM-1 and sICAM-1 were significantly reduced in group C (P<0.05, respectively), but remained unaffected in groups A, B and D. Thus, short term administration of vitamins C (2 g/day) and E (800 IU/day) reduces serum levels of IL-1b, IL-6, sVCAM-1 and sICAM-1, and improves forearm vasodilatory response to reactive hyperemia in healthy young smokers, while monotherapy with vitamin C alone is ineffective.
Atherosclerosis 2003 Oct
PMID:Effects of combined administration of vitamins C and E on reactive hyperemia and inflammatory process in chronic smokers. 1461 6

Inflammation and the recruitment of monocytes into the artery wall are thought to be important aspects in the initiation and progression of atherosclerosis. The present study was designed to examine the effects of a rigorous diet and exercise intervention on plasma lipids and inflammatory and circulating adhesion molecules. Twenty postmenopausal women at risk for coronary artery disease (CAD) were placed on a high-fiber, low-fat diet, where food was provided ad libitum and daily aerobic exercise, primarily walking, was performed. In each subject, pre- and post-intervention fasting blood was drawn for serum lipid, insulin, glucose, C-reactive protein (CRP), serum amyloid A (SAA), interleukin-6 (IL-6) and both soluble (s) intracellular and vascular adhesion molecule (sICAM-1 and sVCAM-1) were measured. After 2 weeks, significant reductions in body mass index (BMI) (P <.001), glucose (P <.05), insulin (P <.01), all serum lipids, and total cholesterol (total-C):high-density lipoprotein-cholesterol (HDL-C) (P <.01). Reductions in homeostasis model assessment for insulin resistance (HOMA-IR) (P <.01), CRP (P <.01), SAA (P <.01) and sICAM-1 (P <.05) were noted, as well as an increase in the quantitative insulin sensitivity check index (P <.05). Reductions were also noted in 5 women not using hormone replacement therapy (HRT). No significant reductions were found in IL-6 or sVCAM-1 in response to the intervention. Overall, this intervention resulted in improved metabolic and lipid profiles, reduced inflammatory, and cell adhesion molecules in postmenopausal women in the absence of caloric restriction. The rapid improvements may reduce the risk of acute myocardial infarction (MI), and if sustained, these changes may mitigate the risk for atherosclerosis progression and its clinical consequences.
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PMID:Effect of diet and exercise intervention on inflammatory and adhesion molecules in postmenopausal women on hormone replacement therapy and at risk for coronary artery disease. 1501 51

The potential effect of iron depletion by blood donation and its relevance to cardiovascular diseases are still under debate. Markers of vascular integrity are increasingly applied in investigations of atherothrombotic diseases. In this study, we investigated whether a lower iron status through blood donation was associated with markers of vascular integrity (circulating oxidised LDL, sICAM-1, sVCAM-1 and vWF-antigen) by comparing healthy male voluntary donors to non-donors, taking into account differences in baseline characteristics. Two fasting blood samples were collected within 1 week from 41 donors and 39 non-donors. The iron status was estimated by measuring the concentration of plasma iron, ferritin, haemoglobin and hematocrit. The markers of iron status were all significantly lower in donors compared to non-donors, especially for ferritin concentrations. However, the lower iron status by blood donation was not reflected in the concentrations of OxLDL, sICAM-1, sVCAM-1 and vWF-antigen in men after adjustment for BMI and ratio total/HDL cholesterol. In order to avoid possible selection-bias related to donorship, we have additionally investigated the difference in marker concentrations within the non-donors, comparing low- and high-ferritin concentrations. This analysis suggests that ferritin concentration is not associated with in vivo LDL oxidation.
Atherosclerosis 2004 Feb
PMID:Is blood donation induced low iron status associated with favourable levels of OxLDL, s-ICAM-1, sVCAM-1 and vWF-antigen in healthy men. 1526 96

Relatives of subjects with type 2 diabetes carry an increased risk for diabetes and cardiovascular disease. Oxidative modification of low-density lipoprotein (LDL) and proinflammatory processes are believed to have central roles in atherogenesis. We have investigated the susceptibility of LDL to oxidation and circulating cell adhesion molecules in healthy, glucose-tolerant adults (aged 18 to 38 years) with (12 men, 2 women) and without (controls; 12 men, 2 women) a parental history of type 2 diabetes. From fasting blood samples, oxidation of LDL was initiated with copper ions and adhesion molecules were measured using immunoassays. Groups were similar with respect to age, body mass index (BMI), blood pressure, plasma glucose, and serum lipids. Resistance of LDL to oxidation was reduced in offspring of parents with type 2 diabetes (time to Vmax, 80.1 +/- 2.2 v 91.4 +/- 2.6 minutes, P =.003). Plasma hydroperoxides did not differ between groups (1.2 +/- 0.1 v 1.1 +/- 0.1 micromol/L). Soluble intracellular adhesion molecule-1 (sICAM1) was elevated in offspring compared with controls (571 +/- 20 v 447 +/- 20 microg/L, P =.0002). Soluble vascular cell adhesion molecule-1 (sVCAM-1) (1,184 +/- 76 v 1084 +/- 56 microg/L, P =.31) and E-selectin (53 +/- 8 v 53 +/- 7 microg/L, P =.98) did not differ between groups. Reduced resistance of LDL to oxidation and increased circulating sICAM-1 in young healthy adult offspring of parents with type 2 diabetes may be intrinsic to increased risk of atherosclerosis in these subjects.
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PMID:Susceptibility of low-density lipoprotein to oxidation and circulating cell adhesion molecules in young healthy adult offspring of parents with type 2 diabetes. 1516 24


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