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)

Dietary antioxidants are reported to suppress cellular expression of chemokines and adhesion molecules that recruit monocytes to the artery wall during atherosclerosis. In the present study we measured the effect of feeding apoE*3 Leiden mice or their non-transgenic (C57BL) littermates with atherogenic diets either deficient in, or supplemented with, dietary antioxidants (vitamin E, vitamin C and beta-carotene) for 12 weeks, on serum levels of CC (JE/MCP-1) and CXC (KC) chemokines and soluble adhesion molecules (sVCAM-1, sICAM-1) and atherosclerotic lesion size. ApoE*3 Leiden mice developed gross hypercholesterolaemia, and markedly accelerated (10-20 fold; P < 0.0001) atherogenesis, compared with non-transgenic animals. Antioxidant consumption reduced lesion area in non-transgenic, but not apoE*3 Leiden, mice. Serum sVCAM-1 and sICAM-1 levels were significantly (P<0.0001) increased (sVCAM-1 up to 3.9 fold; sICAM-1 up to 2.4 fold) by 4-8 weeks in all groups, and then declined. The initial increase in the concentration of adhesion molecules was reduced by 38%-61% (P < 0.05) by antioxidant consumption, particularly in non-transgenic mice. By contrast, serum chemokine levels tended to increase more rapidly from baseline in apoE*3 Leiden mice, compared with non-transgenic animals, but were unaffected by dietary antioxidants. We conclude that dietary antioxidants reduce circulating soluble adhesion molecules and atherosclerosis in C57BL mice.
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PMID:Dietary antioxidants decrease serum soluble adhesion molecule (sVCAM-1, sICAM-1) but not chemokine (JE/MCP-1, KC) concentrations, and reduce atherosclerosis in C57BL but not apoE*3 Leiden mice fed an atherogenic diet. 1640 53

There is much evidence to suggest the existence of racial differences between blacks and whites in the behaviour of endothelial function. Infective state, sustained by viral or bacterial agents, may injure the endothelial surface favouring the onset and progression of atherosclerotic process, mainly by an inflammatory mechanism. The aim of the study was to investigate endothelial function, expressed as brachial flow-mediated vasodilation (FMV), in black and white healthy subjects, along with antibody titer to cytomegalovirus, hepatitis virus (B, C), herpes virus-1 and 2, Epstein-Barr, Chlamydia pneumoniae and the expression of adhesion molecules. We enrolled 22 young (mean age 27+/-8 years) healthy subjects of black race (10 males) and 20 healthy young subjects (10 males, mean age 28+/-9 years) of white race. Total infectious burden (TIB) was defined as the number of serological positive infections. Black subjects have a reduced brachial FMV (6.9+/-3.5% versus 11.6+/-3.0%, p<0.01) and increased values of hsCRP (0.35+/-0.15 mg/dL versus 0.07+/-0.08 mg/dL, p<0.05), white cells (8578+/-1041/mmc versus 5833+/-998/mmc, p<0.01) and adhesion molecules (respectively: sVCAM-1 945+/-142 versus 779+/-93, sICAM-1 534+/-107 ng/mL versus 325+/-80 ng/mL; both p<0.01) in comparison to white subjects. The total infectious burden in black race was significantly higher than in white race (5+/-1 versus 2+/-1, p<0.01). At the univariate analysis, brachial FMV was significantly related to the levels of adhesion molecules (respectively: sVCAM-1 r=-0.49; sICAM-1 r=-0.50, both p<0.05), hsCRP (r=-0.47, p<0.05) and white blood cells (r=-0.43, p<0.05). TIB was associated with brachial FMV (r=-0.64, p<0.05), sVCAM-1 (r=0.55, p<0.05) and hsCRP (r=0.47, p<0.05). At the multivariate analysis the only predictive variables for brachial FMV were hsCRP, TIB and brachial diameter (respectively: beta=-0.49, -0.19, -0.54, all p<0.05). This study confirms that endothelial reactivity is impaired in young African black patients; moreover its behavior is strictly related to the inflammatory state and to the total infectious burden.
Atherosclerosis 2007 Mar
PMID:Racial difference in endothelial function: role of the infective burden. 1671 54

Statins produce cholesterol-independent, anti-inflammatory effects, which result at least in part from increased endothelial nitric oxide production. These effects may be modulated by polymorphisms in the endothelial nitric oxide synthase (eNOS) gene. Here, we examined whether the T-786C polymorphism of eNOS gene affects the concentrations of markers of atherosclerosis and inflammation (sCD40L, sVCAM-1, sICAM-1, sP-selectin, MCP-1, high sensitivity (hs)-CRP, MMP-2, MMP-9, and TIMP-1). We also studied whether atorvastatin-induced anti-inflammatory effects are modulated by this polymorphism. Healthy male volunteers (N=200), Caucasians, non-smokers, were genotyped for the T-786C polymorphism by restriction fragment length polymorphism. Subjects with TT or CC genotype received placebo for 14 days followed by 14 days of treatment with atorvastatin, 10mg/day p.o. The concentrations of inflammatory markers were measured with ELISA kits or by gelatin zymography. Serum cholesterol and LDL-cholesterol were significantly reduced after atorvastatin treatment in both genotype groups (P<0.05). No significant differences between genotype groups were found in the concentrations of the inflammatory markers after placebo. However, atorvastatin significantly reduced the concentrations of sCD40L, sVCAM-1, sP-selectin and MMP-9 in subjects with CC (but not TT) genotype (P<0.05). While atorvastatin decreased hs-CRP levels in both genotype groups (P<0.05), no significant effects were found on the concentrations of sICAM-1, MCP-1, pro-MMP-9, pro-MMP-2 and TIMP-1. These results suggest no effects for the T-786C polymorphism on the concentrations of inflammatory markers. However, this polymorphism modulates the anti-inflammatory effects of atorvastatin. These findings may be relevant for the primary prevention of cardiovascular events in subjects with CC genotype, who may be at increased cardiovascular risk and could benefit from treatment with statins.
Atherosclerosis 2007 Aug
PMID:Anti-inflammatory effects of atorvastatin: modulation by the T-786C polymorphism in the endothelial nitric oxide synthase gene. 1816 15

Early stages of atherosclerosis are commonly noted in youth. The present study was designed to examine the effects of lifestyle modification in 19 overweight children (age 8-17) who were placed on a high-fiber, low-fat diet in a 2-week residential program where food was provided ad libitum and daily exercise (2-2.5h) was performed. In each subject, pre- and post-intervention fasting blood was drawn to measure serum lipids, oxidative stress marker 8-isoprostaglandin F2alpha (8-iso-PGF2alpha) and generating enzyme myeloperoxidase (MPO), soluble intracellular adhesion molecule (sICAM)-1 and sE-selectin as indicators of endothelial activation, the inflammatory protein C-reactive protein (CRP) and total matrix metalloproteinase-9 (MMP-9). Using subject sera and human aortic endothelial cell (HAEC) culture systems, monocyte chemotactic protein-1 (MCP-1) production, as well as nitric oxide (NO), superoxide and hydrogen peroxide production were measured in vitro by fluorometric detection. After 2 weeks, significant reductions (p<0.05) in all serum lipids (except HDL cholesterol), 8-iso-PGF2alpha, MPO, sICAM-1, sE-selectin, CRP, MMP-9, and cellular MCP-1 production were noted. Additionally, there was a significant decrease in cultured, serum-stimulated HAEC production of superoxide and hydrogen peroxide, and a concomitant increase in NO production (all p<0.01), These results indicate amelioration of several traditional as well as novel factors associated with atherosclerosis after lifestyle modification, even in youth without documented disease.
Atherosclerosis 2007 Mar
PMID:Effect of a short-term diet and exercise intervention in youth on atherosclerotic risk factors. 1705 60

Wild-type mice normally do not develop atherosclerosis, unless fed cholic acid. Uremia is proinflammatory and increases atherosclerosis 6- to 10-fold in apolipoprotein E-deficient mice. This study examined the effect of uremia on lipoproteins, vascular inflammation, and atherosclerosis in wild-type C57BL/6J mice. Uremia was induced by nephrectomy (NX) and increased plasma urea and creatinine concentrations 2.5- to 4.5-fold; control mice were sham operated. After NX, mice were fed a Western-type diet or the same diet with 0.5% cholic acid. Cholic acid-fed NX mice did not thrive and were killed. In NX mice fed the Western-type diet (n = 7), the total plasma cholesterol concentration was similar to that in sham mice (n = 11), but on gel filtration the LDL/HDL cholesterol ratio was increased. HDL from NX mice contained more serum amyloid A and triglycerides and less cholesterol than HDL from sham mice. Plasma concentrations of sICAM-1 and sVCAM-1 and aortic mRNA expression of ICAM-1 and VCAM-1 did not differ between NX and sham mice. Twenty-six weeks after NX, the average oil red O-stained area of the aortic root was similar in NX and sham mice fed the Western-type diet, while it was increased in cholic acid-fed sham mice. The results suggest that moderate uremia neither induces aortic inflammation nor atherosclerosis in C57BL/6J mice despite increased LDL/HDL cholesterol ratio and altered HDL composition.
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PMID:Effect of uremia on HDL composition, vascular inflammation, and atherosclerosis in wild-type mice. 1768 60

The aim of our study was to evaluate the relationship of adiponectin to soluble forms of vascular cell adhesion molecule-1 (sVCAM-1) and intercellular cell adhesion molecule-1 (sICAM-1) in patients with cardiovascular disease or dyslipidemia. Two hundred and sixty-four patients (134 men/130 women, mean age 43.8+/-14.8/46.0+/-14.9 years) of Lipid Center, University Hospital Olomouc, off hypolipidemic therapy for at least 6 weeks, participated in the study. In multiple regression analysis, adiponectin was independently positively associated with serum HDL-cholesterol (p<0.0001) and sVCAM-1 (p<0.0001), female gender (p<0.0001) and negatively with hs-CRP (p=0.014). Serum concentration of adiponectin and sICAM-1 did not correlate but sICAM-1 was independently, positively associated with sVCAM-1 (p<0.0001) and negatively with markers of insulin resistance and inflammation, namely atherogenic index log[triglycerides/HDL-cholesterol] (p<0.0001), hs-CRP (p<0.001) and HOMA (p<0.05). Positive association of adiponectin with HDL-C and negative association with hs-CRP indicate anti-atherogenic properties of adiponectin. The finding of the positive association of adiponectin with sVCAM-1 in patients at risk is unexpected. We hypothesize that adiponectin may be involved (directly or indirectly) in shedding of ectodomains of VCAM-1 from endothelial surface and in this way down-regulates their effects. This process may be protective in the initial stages of atherosclerosis.
Atherosclerosis 2008 Apr
PMID:Positive association of adiponectin with soluble vascular cell adhesion molecule sVCAM-1 levels in patients with vascular disease or dyslipidemia. 1771 16

Recent studies have shown a close correlation between advanced diabetic retinopathy and the late stages of atherosclerosis. The purpose of this study was to analyse the association between diabetic retinopathy and early atherosclerotic changes in adolescents with type 1 diabetes. We studied 28 adolescents with type 1 diabetes. Eight patients with nonproliferative retinopathy were compared with the remaining 20 patients, and with 11 healthy controls. The function of endothelium was assessed by measuring flow-mediated dilatation (FMD), the intima-media thickness (IMT) of the common carotid arteries and adhesion molecules (sICAM-1, sVCAM-1, sE-selectin). In the group with retinopathy FMD equalled 7.8+/-4.1% vs. 12.1+/-5.1% in the control group (p=0.04), and in the group without retinopathy, 7.6+/-5.5% (p=0.04 compared to controls). Higher IMT was found in all patients with diabetes in comparison with healthy controls: 0.49+/-0.06 mm vs. 0.42+/-0.03 mm (p=0.001). Patients with retinopathy had a significantly higher value of IMT in comparison not only with controls but also with patients without complications: 0.56+/-0.06 mm vs. 0.47+/-0.03 mm (p=0.0001). Adhesion molecule levels were not changed in patients with retinopathy. Higher IMT was found in adolescents with diabetic retinopathy in comparison with patients without complications, which may suggest that macrovascular changes are more advanced in these patients than in their diabetic peers without retinopathy.
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PMID:The association of early atherosclerosis and retinopathy in adolescents with type 1 diabetes: preliminary report. 1772 51

Increasing evidence suggests that the postprandial state is a contributing factor to the development of atherosclerosis. To evaluate the effects of acute hyperglycemia on endothelial dysfunction and inflammation, plasma asymmetrical dimethyl-l-arginine (ADMA), intercellular adhesion molecule 1 (sICAM-1), vascular cell adhesion molecule 1, and C-reactive protein (CRP) levels and secretory phospholipase A(2) (sPLA(2)) activities were measured in subjects with normal (n = 35), impaired (IGT) (n = 25), and diabetic (DGT) (n = 20) glucose tolerance. At baseline, plasma ADMA, sICAM-1, and CRP concentrations and plasma sPLA(2) activities were higher in both the IGT and DGT groups than in the normal glucose tolerance group (for each comparison, each P < .001). Patients with DGT have higher plasma ADMA and sICAM-1 concentrations than patients with IGT (for each, P < .001).Two hours after glucose loading, plasma ADMA and CRP concentrations and sPLA(2) activities were significantly elevated in the 3 groups when compared with baseline levels (for each comparison, P < .001). Plasma vascular cell adhesion molecule 1 and sICAM-1 concentrations were found to be elevated from baseline levels after glucose loading in the IGT and DGT groups (for each comparison, P < .001). Correlation analysis at baseline suggested that there was a significant relationship between ADMA and inflammation and soluble adhesion markers in the studied groups. In conclusion, plasma concentrations of ADMA and of inflammation and adhesion molecules were elevated in the prediabetic state. A complex interrelation could exist between ADMA and inflammation, and mechanisms involved in endothelial dysfunction are multifactorial at the prediabetic and diabetic state.
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PMID:The relationship between plasma asymmetrical dimethyl-L-arginine and inflammation and adhesion molecule levels in subjects with normal, impaired, and diabetic glucose tolerance. 1807 67

Posttraumatic stress disorder (PTSD) confers an increased cardiovascular risk. In 14 otherwise healthy patients with PTSD and in 14 age- and gender-matched non-PTSD controls, we investigated whether the categorical diagnosis of PTSD and severity of PTSD symptom clusters (i.e. re-experiencing, avoidance, arousal, and overall score) would be associated with plasma concentrations of three markers of endothelial dysfunction [soluble tissue factor (sTF), von Willebrand factor (VWF), and soluble intercellular adhesion molecule (sICAM)-1]. Compared with controls, patients had significantly higher sTF; this difference became nonsignificant when controlling for psychological distress. VWF and sICAM-1 levels were not significantly different between patients and controls. In the entire sample virtually all PTSD symptom clusters correlated significantly and positively with sTF and VWF but not with sICAM-1. The correlation between symptoms of re-experiencing and sTF was significantly different between patients and controls. Controlling for symptoms of anxiety and depression (i.e. psychological distress) rendered most associations between PTSD symptom clusters and sTF nonsignificant, whereas controlling for age retained significance of associations with VWF. Posttraumatic stress showed a continuous relationship with sTF and VWF, with the former relationship being partly affected by psychological distress. This suggests one mechanism by which posttraumatic stress could contribute to atherosclerosis.
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PMID:Measures of endothelial dysfunction in plasma of patients with posttraumatic stress disorder. 1825 65

Inflammation has been indicated to play a major role in the development of atherosclerosis. The beneficial effect of statins has been suggested to be related to their anti-inflammatory properties. We have studied plasma levels of soluble adhesion molecules in patients with hypercholesterolemia before and after 3 months of treatment with atorvastatin and evaluated possible relations to the mutations in low-density lipoprotein receptor (LDLR) gene. In patients with no LDLR gene polymorphism (group A), lower baseline levels of total cholesterol and LDL cholesterol were found than in patients with LDLR gene polymorphism (group B). The soluble adhesion molecules sICAM-1, sE-selectin and sP-selectin, but not sVCAM-1 and sL-selectin, were higher in group B than in group A. sICAM-1 levels decreased in group A by 7% (p = 0.007) and in group B by 21% (p = 0.039), whereas levels of sVCAM-1 decreased in group A by 12% (p = 0.001) and in group B patients by 19% (p = 0.039). Atorvastatin did not change sE-selectin nor sP-selectin levels in group A. However, in group B, the treatment reduced E-selectin and sP-selectin levels by 39% (p = 0.007) and 24% (p = 0.007), respectively. Atorvastatin attenuates the inflammatory reaction in hypercholesterolemic patients, but in patients with LDLR gene polymorphism, this effect is more profound.
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PMID:The effect of atorvastatin treatment on lipid profile and adhesion molecule levels in hypercholesterolemic patients: relation to low-density lipoprotein receptor gene polymorphism. 1837 26


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