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 effects of 12 months hormone replacement therapy (HRT) on biochemical markers associated with endothelial function were studied in 98 postmenopausal women with CAD, who were randomized to transdermal HRT or a control group. A significant reduction in the levels of von Willebrand factor in the HRT-group compared to controls was seen after 3 months, maintained after 12 months (p <0.001). Significant reduction in the HRT-group compared to controls was also seen in VCAM-1 after 3 months, sustained after 12 months (p = 0.013 and p = 0.045, respectively), and E-selectin was reduced by about 20% after 3 months on HRT, the reduction being statistically significant after 12 months (p <0.001). Significantly reduced levels of ICAM-1 were also seen after 12 months (p = 0.048). No effects could be observed on tPA-antigen or thrombomodulin. The reduction in procoagulant and proinflammatory markers of endothelial function after long-term transdermal HRT could indicate a beneficial effect on the endothelium and thus a potentially modulating effect on the progression of atherosclerosis in women with CAD.
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PMID:Reduced expression of endothelial cell markers after long-term transdermal hormone replacement therapy in women with coronary artery disease. 1089 53

Intercellular adhesion molecule-1 (ICAM-1) is expressed by endothelial and other cell types and participates in inflammation and atherosclerosis. It serves as a ligand for leukocyte function-associated antigen-1 on leukocytes and is partially responsible for the adhesion of lymphocytes, granulocytes, and monocytes to cytokine-stimulated endothelial cells and the subsequent transendothelial migration. Its expression on endothelial cells is increased in inflammation and atherosclerosis. As it has been suggested that insulin and hyperinsulinemia may have a role in atherogenesis, we have now investigated whether insulin has an effect on the expression of ICAM-1 on human aortic endothelial cells (HAEC). HAEC were prepared from human aortas by collagenase digestion and were grown in culture. Insulin (100 and 1000 microU/mL) caused a decrease in the expression of ICAM-1 (messenger ribonucleic acid and protein) by these cells in a dose-dependent manner after incubation for 2 days. This decrease was associated with a concomitant increase in endothelial nitric oxide synthase (NOS) expression also induced by insulin. To examine whether the insulin-induced inhibition of ICAM-1 was mediated by nitric oxide (NO) from increased endothelial NOS, HAEC were treated with N(omega)-nitro-L-arginine, a NOS inhibitor. N(omega)-Nitro-L-arginine inhibited the insulin-induced decrease in ICAM-1 expression in HAEC at the messenger ribonucleic acid and protein levels. Thus, the inhibitory effect of insulin on ICAM-1 expression is mediated by NO. We conclude that insulin reduces the expression of the proinflammatory adhesion molecule ICAM-1 through an increase in the expression of NOS and NO generation and that insulin may have a potential antiinflammatory and antiatherosclerotic effect rather than a proatherosclerotic effect.
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PMID:Insulin inhibits the expression of intercellular adhesion molecule-1 by human aortic endothelial cells through stimulation of nitric oxide. 1090 10

Mononuclear cells and platelets are intimately involved in the pathogenesis and complications of cardiovascular disease. Platelet activation has been reported in hypertension, though the activation-state of monocytes has received less attention. In this study the adhesiveness of monocytes and platelets was assessed and any relationship between the adhesive properties of these cellular elements and plasma levels of soluble adhesion molecules and blood pressure parameters determined. Fifty six elderly volunteers, of whom 32 were classified hypertensive (daytime SBP > or = 135 mmHg), underwent 24 h blood pressure monitoring, assessment of monocyte and platelet adhesion and measurement of the plasma soluble adhesion molecules ICAM-1, L-selectin, E-selectin and vWF. In the elderly hypertensive subjects, monocyte adhesion to collagen coated (P < 0.05) and tissue culture plastic microwells (P < 0.05) was significantly elevated and circulating levels of soluble ICAM-1 (P < 0.01) and soluble E-selectin (P < 0.05) were significantly raised compared to their normotensive counterparts. A significant correlation was found to exist between monocyte adhesion to collagen and daytime pulse pressure (r = 0.39, P < 0.01) and also between plasma levels of soluble E-selectin and clinic DBP (r = 0.40, P < 0.001). The increased monocyte adhesion witnessed in hypertensive subjects and with increasing pulse pressure may contribute to the increased risk of cardiovascular disease in hypertension. Whether this increased adhesiveness is a property of the monocytes. or reflects endothelial cell activation, remains to be determined.
Atherosclerosis 2000 Aug
PMID:Mononuclear cell adhesion to collagen ex vivo is related to pulse pressure in elderly subjects. 1092 23

T cells have roles in the pathogenesis of native coronary atherosclerosis (CA) and transplant-associated coronary artery disease (TCAD). The mechanisms by which T cells interact with other cells in these lesions are not fully known. CD154 is an activation-induced CD4+ T cell surface molecule that interacts with CD40+ target cells, including macrophages and endothelial cells, and induces the production of pro-inflammatory molecules, including CD54 (ICAM-1) and CD106 (VCAM-1). To investigate whether CD154-CD40 interactions might be involved in the pathogenesis of CA or TCAD we performed immunohistochemical studies of CD154 and CD40 expression on frozen sections of coronary arteries obtained from cardiac allograft recipients with CA (n=10) or TCAD (n=9). Utilizing four different anti-CD154 mAb we found that CD154 expression was restricted to infiltrating lymphocytes in CA and TCAD. CD40 expression was markedly up-regulated on intimal endothelial cells, foam cells, macrophages and smooth muscle cells in both diseases. Dual immunolabeling demonstrated many CD40+ cells co-expressed CD54 and CD106. The extent of CD40, CD54 and CD106 expression showed statistical significant correlation with the severity of disease and the amount of intimal lymphocytes. Together these studies demonstrate the presence of activated CD154+ and CD40+ cells in both CA and TCAD lesions and suggest that CD154-mediated interactions with CD40+ macrophages, foam cells, smooth muscle cells and/or endothelial cells may contribute to the pathogenesis of these diseases.
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PMID:Analysis of CD154 and CD40 expression in native coronary atherosclerosis and transplant associated coronary artery disease. 1099 75

Enhanced monocyte-endothelial cell interactions have been documented in diabetes. Because adherence of monocytes to the endothelium is one of the earliest events in the development of atherosclerosis, its alteration may represent one of the mechanisms leading to accelerated atherosclerosis in diabetic patients. Previous studies have suggested that lipoprotein oxidation and protein glycation may contribute to the increased monocyte binding to the diabetic vasculature. Based on the recent finding that gliclazide has free-radical scavenging activity, we examined the ex vivo and in vitro effects of this drug on human monocyte binding to endothelial cells. Our results demonstrate that short-term administration of gliclazide to patients with type 2 diabetes lowers the enhanced adhesion of diabetic monocytes observed before gliclazide treatment (163+/-24% over control values, p<0.005) to levels similar to those observed in controls. They also show that gliclazide (10 microg/ml) reduces in vitro by approximately 35% both oxidized low-density lipoprotein (LDL)- and glycated albumin-induced monocyte adhesion to endothelial cells. Based on these results, we next investigated the molecular mechanisms responsible for the inhibitory effect of gliclazide on glycated albumin-induced monocyte adhesion to endothelium. In glycated albumin-treated endothelial cells, we observed induction of cell-associated expression of E-selectin (ELAM-1; 170+/-10% over control values, p<0.005), intercellular cell adhesion molecule-1 (ICAM-1; 131+/-8% over control values, p<0.005) and vascular cell adhesion molecule-1 (VCAM-1; 134+/-8% over control values, p<0.005), augmentation in the levels of the transcripts of these molecules, and an increase in the DNA binding of NF-kappaB in the promoters of these antigens. Gliclazide markedly inhibited the induction of all these parameters. Because the oxidative stress-sensitive transcription factor NF-kappaB is implicated in endothelial cell activation, the observed inhibitory effect of gliclazide on NF-kappaB activation and glycated albumin-induced expression of DNA binding activity for the NF-kappaB site in the ELAM-1, ICAM-1 and VCAM-1 promoters seems to be due to its antioxidant properties. These results suggest that gliclazide, by its ability to reduce endothelial activation, may exert potential beneficial effects in the prevention of atherosclerosis associated with type 2 diabetes.
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PMID:Effect of gliclazide on monocyte-endothelium interactions in diabetes. 1100 31

In atherosclerosis, leukocyte migration into the plaque is thought to occur across the endothelium of the arterial lumen. However, intraplaque microvessels have been noted. While the significance of, and stimuli for these are uncertain, it seems possible that they may represent a second portal of entry for leukocytes into the plaque. This study performed a basic characterization of intraplaque microvessels and tested the hypothesis that the novel angiogenic factor thymidine phosphorylase (TP) is expressed in atherosclerosis. Immunocytochemistry was performed on aortic and coronary plaques and morphometry on coronary plaques. In plaques from both sites, macrophages, foam cells, and giant cells were immunoreactive for the angiogenic factors TP and vascular endothelial growth factor. Venule-like intraplaque microvessels expressed endothelial leukocyte adhesion molecules HLA-DR and ICAM-1, in contrast to the endothelium overlying the plaque. In coronary plaques, there was a correlation between severity of stenosis and plaque microvascular density. These results are consistent with a role for plaque macrophage/foam cell TP in stimulating plaque angiogenesis. While attention has focused on dysfunction of the endothelium overlying the plaque, microvascular endothelium may also represent a portal of entry for leukocytes into established plaques.
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PMID:Expression of angiogenic factor thymidine phosphorylase and angiogenesis in human atherosclerosis. 1100 1

Macrophage infiltration into the subendothelial space at lesion prone sites is the primary event in atherogenesis. Inhibition of macrophage homing might therefore prevent atherosclerosis. Since HDL levels are inversely correlated with cardiovascular risk, their effect on macrophage homing was assessed in apoE-deficient (apoE-/-) mice. Overexpression of human apolipoprotein AI in apoE-/- mice increased HDL levels 3-fold and reduced macrophage accumulation in an established assay of leukocyte homing to aortic root endothelium 3.2-fold (P<0.005). This was due to reduced in vivo betaVLDL oxidation, reduced betaVLDL triggered endothelial cytosolic Ca2+ signaling through PAF-like bioactivity, lower ICAM-1 and VCAM-1 expression, and diminished ex vivo leukocyte adhesion. Adenoviral gene transfer of human PAF-acetylhydrolase (PAF-AH) in apoE-/- mice increased PAF-AH activity 1.5-fold (P<0.001), reduced betaVLDL-induced ex vivo macrophage adhesion 3.5-fold (P<0.01), and reduced in vivo macrophage homing 2.6-fold (P<0.02). These inhibitory effects were observed in the absence of increased HDL cholesterol levels. In conclusion, HDL reduces macrophage homing to endothelium by reducing oxidative stress via its associated PAF-AH activity. This protective mechanism is independent of the function of HDL as cholesterol acceptor. Modulation of lipoprotein oxidation by PAF-AH may prevent leukocyte recruitment to the vessel wall, a key feature in atherogenesis.
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PMID:HDL-associated PAF-AH reduces endothelial adhesiveness in apoE-/- mice. 1102 87

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

In patients with coronary artery disease (CAD), azithromycin therapy is associated with decreased cytokine levels and overall reduction of inflammation. Chlamydia pneumoniae (C.Pn) is a common pathogen that may be an important factor in the development and progression of atherosclerosis. Cell-adhesion molecules have an important role in recruitment of inflammatory cells during plaque development and are expressed by endothelial cells on activation. We sought to define the effect of treatment with azithromycin on circulating levels of soluble vascular cell-adhesion molecule (VCAM-I), intercellular adhesion molecule (ICAM-1), and E-selectin in patients with CAD. Plasma concentrations of VCAM-1, ICAM-1, and E-selectin were measured in 40 patients with documented CAD and a positive (> or = 1:16) immunoglobulin G (IgG) titer against C.Pn, 20 subjects with normal coronary arteries, and 14 healthy volunteers. Patients were assigned randomly to receive either 500 mg/wk of azithromycin or placebo for 3 months. Serum samples were obtained at baseline, at 3 months, and during the follow-up visit at 6 months. Patients with documented CAD exhibited elevation of VCAM-1 (535 +/- 227 ng/ ml; p = 0.0001) and E-selectin (69 +/- 29 ng/ml; p = 0.006), but not ICAM-1 (321 +/- 65 ng/ml) concentrations as compared with the patients with angiographically proven normal coronary arteries (252 +/- 80; 50 +/- 22; and 311 +/- 40 ng/ml) and healthy controls (110 +/- 18; 29 +/- 2; and 238 +/- 47 ng/ml, respectively). Prolonged treatment with azithromycin did not significantly affect the plasma levels of soluble VCAM-1, ICAM-1, and E-selectin. Soluble markers of endothelial activation are markedly increased in patients with documented CAD as compared with those with normal coronary arteries and healthy controls. Despite substantial heterogeneity in plasma E-selectin, ICAM-1, and VCAM-1 levels, long-term azithromycin treatment did not affect plasma levels of these adhesion molecules, indicative of endothelial activation, over a period of 6 months.
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PMID:The effect of chronic azithromycin therapy on soluble endothelium-derived adhesion molecules in patients with coronary artery disease. 1102 57

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


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