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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study was initiated to describe the relationships between plasma glucose and insulin responses to oral glucose and the concentrations of partially oxidized low density lipoprotein (poxLDL) and soluble intercellular adhesion molecule-1 (sICAM-1) in 23 healthy, non-diabetic volunteers. Results demonstrated that plasma glucose (r=0.65, P<0.002) and insulin (r=0.58, P<0.007) responses to a 75-g oral glucose challenge were highly correlated to poxLDL concentrations. Plasma glucose (r=0.63, P<0.002) and insulin (r=0.68, P<0.001) concentrations also significantly correlated with sICAM-1 concentrations. Furthermore, concentrations of poxLDL and sICAM-1 were significantly related (r=0.55, P<0.001). These relationships remained statistically significant when adjusted for differences in age, gender, body mass index, and lipoprotein concentrations. These results provide further evidence that circulating LDL particles are more highly oxidized in insulin resistant states, and demonstrate the presence of an in vivo relationship between insulin resistance, LDL oxidized state, and sICAM-1 concentrations. These results help explain why soluble forms of adhesion molecules are increased in clinical conditions characterized by insulin resistance, and support the possibility that LDL oxidizability is increased in insulin resistant subjects, and that the increase in sICAM-1 results from stimulation of cellular adhesion molecules by more highly oxidized LDL.
Atherosclerosis 2000 Sep
PMID:The relationship between plasma glucose and insulin responses to oral glucose, LDL oxidation, and soluble intercellular adhesion molecule-1 in healthy volunteers. 1099 56

High serum concentrations of soluble adhesion molecules are present in diabetics, but whether similar levels are present in patients with impaired glucose tolerance (IGT) is unclear. We measured serum concentrations of soluble intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), and sE-selectin in 128 nondiabetic Japanese subjects. The concentrations of sICAM-1, sVCAM-1, and sE-selectin in IGT patients (n=47) were not different from those in subjects with normal glucose tolerance (NGT; n=81). IGT patients were subdivided into two groups by the results of 75 g OGTT, those with low- (hypoinsulinemia; n=23) or high-insulin (hyperinsulinemia; n=24). The levels of sICAM-1 and sVCAM-1 were not different among NGT and IGT with high-insulin or with low-insulin. However, sE-selectin concentrations were significantly higher in IGT patients with high-insulin than in NGT and IGT with low-insulin (61.1+/-3.4, 47.1+/-1.8 and 43.7+/-3.9 ng/ml, respectively, P<0.001). Adjustment for age and gender did not influence the results. Serum sE-selectin concentrations correlated significantly with the area under the curve of insulin (AUC(insulin)), AUC(glucose), diastolic blood pressure, and triglyceride levels (r=0.35, 0.26, 0.18 and 0.21, respectively), and negatively with HDL-cholesterol levels (r=-0.20). Multiple regression analysis showed that AUC(insulin) was the only independent factor that correlated with sE-selectin levels (P<0.001). Our results indicate that hyperinsulinemia/insulin resistance may be responsible for the elevation of sE-selectin levels.
Atherosclerosis 2000 Oct
PMID:High serum concentrations of soluble E-selectin in patients with impaired glucose tolerance with hyperinsulinemia. 1099 70

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

Oxidative modification of low-density lipoproteins (LDL) is important in the etiology and pathogenesis of atherosclerosis. Alterations of function and structure of vascular endothelial cells (ECs) mark the early stages of the development of atherogenesis. Human umbilical vein endothelial cells (HUVECs) were used to investigate the role of angelica in human vascular ECs damage. HUVECs incubated with 0.1 mg/ml of ox-LDL for 24 hours exhibited more pronounced morphological change, such as: cell shrinkage, disappearance of microvilli on EC surface, cellular membrane rupture, intercellular space enlargement, and significantly increased intercellular adhesion molecule-1 (ICAM-1) expression. The effects of ox-LDL on morphology and ICAM-1 can be reversed by Angelica. The effect of Angelica on Cu2+-catalyzed LDL oxidation was also studied and it was demonstrated that Angelica produced a concentration dependent inhibition of LDL oxidation as assessed by thiobarbituric acid-reactive substances (TBARS). Our findings indicate that Angelica has protective effect against ox-LDL induced damage on cultured HUVECs, an antioxidant effect on LDLs, and an inhibiting effect on ox-LDL induced ICAM-1 expression of endothelial cells. These findings further provided experiment proofs for the antiatherogenesis effect of Angelica.
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PMID:Angelica protects the human vascular endothelial cell from the effects of oxidized low-density lipoprotein in vitro. 1108 69

The purpose of this study was to assess the expression of cell adhesion molecules ICAM-1 (intercellular adhesion molecule-1) and VCAM-1 (vascular cell adhesion molecule-1) in endothelial cell-derived foam cells. Hamster aortic endothelial cells (HAEC) in culture were exposed to hypercholesterolemic or normal homologous serum for 24 h. At the end of the incubation period, HAEC exposed to hypercholesterolemic serum exhibited numerous lipid droplets and had a general aspect of foam cells. When examined for the expression of ICAM-1 and VCAM-1 (by indirect immunofluorescence) normal HAEC expressed constitutively (to low level) on their surface these adhesion molecules; however HAEC-derived foam cells failed to display any labeling. To further assess these results, HAEC were first incubated with normal or hypercholesterolemic sera (as above) and then exposed to freshly isolated normal hamster blood monocytes. These experiments showed that monocytes adhered in small number to normal cells and failed to adhere to the surface of HAEC-derived foam cells. Together these data indicate that endothelial cell-derived foam cells: a) do not express ICAM-1 and VCAM-1 on their surface; b) have low or no adhesion properties for monocytes and c) may represent an appropriate experimental model to study the cellular alterations that take place in the advanced stages of atherosclerosis.
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PMID:Endothelial cell-derived foam cells fail to express adhesion molecules (ICAM-1 and VCAM-1) for monocytes. 1108 8

The main objective of this study was to determine the influence of the degree of low density lipoprotein (LDL) oxidation and the location of oxidized LDL (oxLDL) on expression of adhesion molecules on endothelial cells (EC). OxLDL preparations 1-4 with different degrees of oxidative modification were studied. All preparations of oxLDL, after addition to the medium, stimulated the expression of intercellular adhesion molecule-1 (ICAM-1) by human umbilical vein endothelial cells (HUVEC) as determined by cell-ELISA. Concentration-dependent studies examining ICAM-1 expression by HUVEC showed that the minimal concentration of oxLDL which significantly stimulated ICAM-1 expression was 5 microg/ml, suggesting that the predicted physiological concentration of oxLDL in plasma may be not high enough to elicit a substantial increase of ICAM-1 expression in EC. In contrast, very small amounts (0.15 microg/well) of oxLDL-3 and 4, the more heavily oxidized LDL preparations, stimulated effectively ICAM-1 expression by HUVEC when located below the endothelial cell monolayer by immobilizing to type I collagen. The results suggest that the increased expression of ICAM-1 induced by accumulated oxLDL may be one of the mechanisms by which oxLDL contributes to atherogenesis.
Atherosclerosis 2001 Jan
PMID:Expression of adhesion molecules by human endothelial cells exposed to oxidized low density lipoprotein. Influences of degree of oxidation and location of oxidized LDL. 1113 85

Although cardiac ischemia is usually characterized as a disease of the myocyte, it is clear that the vasculature, and especially endothelial cells, is also a major target of this pathology. Indeed, using a rat model of ischemia/reperfusion, we were able to detect severe endothelial dysfunction (assessed as a decreased response to acetylcholine) after acute or chronic reperfusion. Given the essential role of the endothelium in the regulation of vascular tone, as well as platelet and leukocyte function, such a severe dysfunction could lead to an increased risk of vasospasm, thrombosis and accelerated atherosclerosis. This dysfunction can be prevented by free radical scavengers and by exogenous nitric oxide. Endothelial dysfunction can also be prevented by preconditioning with brief periods of intermittent ischemia, thus extending to coronary endothelial cells the concept of endogenous protection previously described at the myocyte level. Experiments performed on cultured cells showed that the endothelial protection induced by free radical scavengers or by preconditioning was due to a lesser expression of endothelial adhesion molecules such as intercellular adhesion molecule-1, leading to a lesser adhesion of neutrophils to endothelial cells. Identification of the mechanisms of this protection may lead to the development of new strategies aimed at protecting the vasculature in ischemic heart diseases.
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PMID:Coronary endothelial dysfunction after ischemia and reperfusion: a new therapeutic target? 1115 Oct 23

-The role of the humoral immune response to oxidized low density lipoprotein (Ox-LDL) in atherogenesis is unclear and available studies are contradictory. The aims of the present study were (1) to compare antibody titers to modified LDL in a group of patients with hypercholesterolemia (n=102) with those in matched controls (n=102), (2) to analyze whether these titers were related to atherosclerosis development as measured by ultrasound, and (3) to analyze whether these titers were related to soluble cell adhesion molecules and secretory type II phospholipase A(2) in plasma. The results showed that male patients with hypercholesterolemia had lower immunoglobulin G (IgG) titers compared with those in healthy controls. In the control group, there was an inverse correlation between intima-media thickness of the carotid artery bulb and IgM titers against Ox-LDL and malondialdehyde-LDL (r=-0.35, P:=0.001; and r=-0.31, P:=0.003, respectively). In the patient group, however, only weak associations were seen. IgG titers were positively associated with soluble intercellular adhesion molecule-1, soluble E-selectin, and secretory type II phospholipase A(2). Taken together, the results of this study support the concept that the humoral immune response against Ox-LDL may be protective in early atherosclerosis. The pattern, however, is complex, and the role of the immune response may differ in different patient groups as well as at different stages of the disease.
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PMID:Antibodies to oxidized LDL in relation to carotid atherosclerosis, cell adhesion molecules, and phospholipase A(2). 1115 64

Cellular adhesion molecules play a pivotal role in the pathogenesis of atherosclerosis by mediating the adherence of blood leukocytes. Since hyperhomocysteinemia appears to be an independent risk factor for the development of atherosclerosis, in this study we investigated the effect of homocysteine on basal and TNF-alpha-induced expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell-adhesion molecule-1 (VCAM-1), and endothelial leukocyte adhesion molecule-1 (E-selectin) on human umbilical-vein endothelial cells. Incubation of endothelial cells with homocysteine resulted in dose-dependent reduction in TNF-alpha-induced (5 ng/ml) expression of VCAM-1, E-selectin, and ICAM-1 (the latter less pronounced). This effect was found to be specific since other thiol compounds-cysteine and glutathione-did not mimic homocysteine activity. Homocysteine attenuated TNF-alpha-stimulated U-937 adhesion to the endothelial monolayer and reduced TNF-alpha-induced activation of the transcription factor NF-kappaB, indicating that NF-kappaB inhibition may play a role in inhibiting expression of adhesion molecules in endothelial cells.
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PMID:Homocysteine inhibits TNF-alpha-induced endothelial adhesion molecule expression and monocyte adhesion via nuclear factor-kappaB dependent pathway. 1116 39

Soluble intercellular adhesion molecule-1 (sICAM-1) and vascular cellular adhesion molecule-1 (sVCAM-1) were measured alongside flow-mediated vasodilation (FMD) in 34 patients with intermittent claudication and 14 control subjects. Patients with plasma sICAM-1 >253 ng/mL (median value) showed lower FMD than those with sICAM-1 < 253 ng/mL (5.6 +/- 1.8% vs 9.6 +/- 4.2%, p < 0.01). Similarly, in the 17 patients with plasma sVCAM-1 > 414 ng/mL, FMD was lower than in the remaining 17 patients (6.1 +/- 1.9% vs 9.2 +/- 4.5%, p < 0.05). Additionally, when endothelial dysfunction was defined as FMD < or = 5.5%, patients with FMD below this value had higher plasma concentrations of sICAM-1 and sVCAM-1 than those with FMD > 5.5%. Therefore, our findings indicate a close association between elevated plasma levels of adhesion molecules and endothelial dysfunction. As impaired endothelial function is one of the first steps in atherogenesis, our findings have clinical relevance since they serve as the basis for further evaluation of sICAM-1 and sVCAM-1 as potential plasma markers for progression of atherosclerosis in a population at high risk.
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PMID:High levels of adhesion molecules are associated with impaired endothelium-dependent vasodilation in patients with peripheral arterial disease. 1120 90


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