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)

Inflammatory mediators, such as tumor necrosis factor alpha (TNF), may be important in the pathogenesis of atherosclerosis. Interactions between TNF and its target cell(s) requires the presence of specific receptors on the latter. Plasma levels of the two soluble forms of these receptors (tumor necrosis factor receptors, (sTNFr)) and TNF itself were measured by ELISA in 20 patients with peripheral vascular disease (PVD), 20 survivors of a myocardial infarction, and 20 age and sex matched controls. Levels of the p55 variant of the sTNFr were unchanged but levels of the p75 variant were increased in both groups of patients (ANOVA both P < 0.01). TNF was also raised in both groups of patients (both P < 0.05) but levels did not correlate with either sTNFr. In atherosclerosis, increased levels of p75 sTNFr may be further evidence of inappropriate leukocyte activation but unlikely to modulate the effect of free plasma TNF.
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PMID:Increased levels of soluble tumor necrosis factor receptors in atherosclerosis: no clear relationship with levels of tumor necrosis factor. 979 95

In mice with genetically engineered high levels of plasma low density lipoprotein (LDL), we tested the hypothesis that an increase in the dietary content of monounsaturated fatty acids but not of polyunsaturated fatty acids would promote atherosclerosis. The mouse model used was an LDL receptor-null, human apoB100-overexpressing strain. Six experimental groups of 19 to 38 mice of both sexes were established when the animals had reached 8 weeks of age. For the next 16 weeks, individual groups were fed either a commercial diet or prepared diets including fat as 10% of energy, with 5 different fatty acid enrichment patterns including the following: saturated (sat), cis and trans monounsaturated (mono), and n-3 and n-6 polyunsaturated (poly). Highly significant differences (ANOVA, P<0. 0001) in LDL cholesterol (in mg/dL) were found, with the rank order at 16 weeks being trans mono (mean, 1390)>sat (922)=cis mono (869)=n-6 poly (868)>n-3 poly (652)>commercial diet (526). Significant elevations in very low density lipoprotein cholesterol were also found in the trans and cis mono and sat groups, and triacylglycerol concentrations were also elevated in all groups. High density lipoprotein cholesterol concentrations were consistently low (20 to 50 mg/dL) in all groups. Highly significant differences (ANOVA, P<0.0001) in atherosclerosis, quantified by measurement of aortic cholesteryl ester concentration (mg/g protein) among dietary fatty acid groups were found, with the order being trans mono (mean, 50.4)>sat (35.6)=cis mono (34.6)>n-6 poly (18. 3)=n-3 poly (9.7)=commercial diet (7.8). Therefore, in this mouse model of hypercholesterolemia, dietary cis or trans monounsaturated fat did not protect against atherosclerosis development, whereas aortic atherosclerosis in either of the polyunsaturated fat groups was significantly less than in the saturated fat group.
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PMID:Dietary monounsaturated fatty acids promote aortic atherosclerosis in LDL receptor-null, human ApoB100-overexpressing transgenic mice. 981 23

The effect of natural androgens on serum lipids and atherosclerosis is controversial. We therefore studied this important issue prospectively in an animal model of atherosclerosis. Eighty male rabbits were randomized to bilateral castration, and 20 animals were sham operated. The castrated rabbits were randomized to 500 mg oral dehydroepiandrosterone (DHEA) daily, 80 mg oral testosterone undecanoate (TU) daily, or 25-mg intramuscular injection of testosterone enanthate (TE) twice weekly, whereas the fourth castrated group (placebo) and the sham-operated rabbits did not receive any hormones. All animals were fed a cholesterol-rich diet during the 30-week treatment period. Average serum lipids and atherogenic lipoproteins were higher in the placebo group than in the other groups (ANOVA, P<0.0001). Aortic atherosclerosis, as evaluated by the cholesterol content (nmol/mg protein), was also highest in the placebo group (308+/-39) and lowest in the TE group (61+/-12), but was intermediate in the DHEA (155+/-30), TU (191+/-43), and sham operation (162+/-29) groups (ANOVA, P<0.0001). ANCOVA indicated that the androgen effect on aortic atherosclerosis was only in part explained by the changes in lipoproteins. Aortic estrogen receptor contents were significantly lower in the androgen-treated groups than in the control groups, whereas there was no difference in aortic androgen receptor contents between groups. Natural androgens inhibit aortic atherosclerosis in castrated male rabbits only partly through a lipid-mediated effect.
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PMID:Natural androgens inhibit male atherosclerosis: a study in castrated, cholesterol-fed rabbits. 1020 49

Previous in vivo studies in humans and dogs have revealed an atherosclerosis-like phenomenon in which lipid penetration within arterial prosthesis wall was observed. The primary goal of the present study was therefore to investigate the occurrence of this lipid retention in ePTFE prostheses implanted in humans and therefore identify potential risk factors related to this phenomenon. Lipid uptake in 367 ePTFE microporous vascular prostheses explanted from humans was studied using Fourier transform infrared spectroscopy. The assignment of the infrared absorption features clearly revealed the presence of strongly bonded unsaturated fatty acids to the microporous structure of the prostheses. A one-way ANOVA statistical analysis showed that the lipid uptake in the synthetic vascular prostheses depended on the duration of implantation of the prosthesis and on the sex of the patient. A two-way ANOVA showed that a relationship existed between the estimated lipid uptake and the internal diameter of the prosthesis. These results confirm that the lipid uptake phenomenon depends on some clinical factors related either to the patients or to the prostheses' morphological parameters.
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PMID:Lipid uptake in synthetic vascular prostheses explanted from humans. 1037 2

1. 'Chelation therapy' with EDTA is being frequently used in patients with cardiovascular disease, despite limited objective evidence of effectiveness. Depressed nitric oxide (.NO)-related endothelial function accompanies atherosclerosis, and even the vascular risk factors alone, and is improved by numerous interventions that also improve prognosis in vascular disease. 2. The aim of the present study was to determine the influence of chelation therapy with EDTA alone and EDTA in combination with B vitamins on endothelial function. 3. After a control series of saline infusions, we examined the effects of a series of EDTA infusions (1.5 g, 10 times over 6 weeks) in eight subjects with coronary artery disease. In addition, because EDTA is commonly supplemented by other components, particularly B group vitamins, we subsequently examined the effect of a similar series of vitamin-supplemented EDTA infusions. 4. Forearm blood flow (FBF) was assessed by plethysmography and graded intrabrachial infusions of the endothelium-dependent vasodilator acetylcholine (ACh) and the endothelium-independent dilator sodium nitroprusside (SNP). 5. There was no difference in vasodilation to either drug after EDTA alone compared with the control periods, but the response to ACh was augmented after combined therapy (P < 0.03, ANOVA). The latter was accompanied by a small but consistent mean (+/- SEM) fall in plasma homocysteine of 1.6 +/- 0.5 mumol/L (P < 0.05). 6. The selective increase in the vasodilator response to ACh after therapy with EDTA and several B group vitamins indicates that NO-related endothelial function was improved. The absence of response to EDTA alone suggests that the supplementary vitamins were necessary for this benefit, which may have been related to the accompanying decrease in plasma homocysteine. These results, along with the current interest in the possible cardioprotective effects of vitamins and the increasing administration of 'chelation therapy', call for more definitive studies on these aspects of 'alternative medicine'.
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PMID:Effects of chelation with EDTA and vitamin B therapy on nitric oxide-related endothelial vasodilator function. 1056 4

Increased level of soluble cell adhesion molecules may be a marker for atherosclerosis and/or reflect complication of the atherosclerotic plaque. To test whether expression of cell adhesion molecules is more pronounced in unstable versus stable coronary plaques, we measured the serum level of soluble E-selectin (sE-selectin) in 99 consecutive patients admitted to the hospital for acute coronary syndromes (ACS) and in 61 patients with chronic coronary artery disease (CAD) using a commercially available ELISA kit. We also measured the sE-selectin concentration in 20 sex- and age-matched subjects without clinical evidence of atherosclerosis, who served as controls. The mean sE-selectin level was higher in both groups of patients compared with controls (ACS, 35.0 +/- 23.4 ng/mL; chronic CAD, 32.9 +/- 21.0 ng/mL; controls, 14.5 +/- 6.6 ng/mL; one-way ANOVA, P = 0.001), but there was no difference between patients with ACS and chronic CAD. Furthermore, there was a trend (P = 0.08) toward a decrease in sE-selectin with an increase in the extent and severity of CAD. In patients with ACS, the in-hospital cardiac event rate was 8%. Although mean sE-selectin concentration tended to be higher in patients with (49.2 +/- 42.1 ng/mL) than in those without (33.8 +/- 21.3 ng/mL) in-hospital cardiac events, the difference was not significant. In 53 patients with ACS, C-reactive protein was measured and showed no correlation with the sE-selectin concentration. These findings show that although sE-selectin concentration is elevated in the presence of clinically relevant atherosclerosis, it does not further increase during the unstable phase of the disease, indicating that sE-selectin is not a reliable indicator of a complicated atherosclerotic plaque.
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PMID:Soluble E-selectin is not a marker of unstable coronary plaque in serum of patients with ischemic heart disease. 1059 Jan 90

Elevated blood cholesterol is a major risk factor for atherosclerosis. Recent studies show that lowering cholesterol reduces the risk of vascular disease, but the precise mechanisms for vascular improvement are not fully understood. Furthermore, it is not known whether the beneficial effects of cholesterol lowering extend to the skin microvasculature. In this unrandomized, open design study, we used iontophoresis and laser Doppler flowmetry to examine forearm skin perfusion in hypercholesterolaemic patients with PAOD before and after cholesterol-lowering therapy with fluvastatin. Endothelium-dependent and -independent vasodilatation were measured following skin iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP), respectively. Before cholesterol-lowering, vascular responses to ACh and SNP were reduced significantly in patients compared with responses in control subjects (p < 0.001 and p < 0.05, ANOVA, respectively). Fluvastatin therapy (40 mg/day) for 24 weeks significantly reduced total cholesterol (7.3+/-0.3 to 6.0+/-0.2 mmol/l, p < 0.001) and LDL cholesterol (5.4+/-0.5 to 4.2+/-0.4 mmol/l, p < 0.01). Vasodilatation to SNP was significantly improved at week 24 (p < 0.05). In patients with hypercholesterolaemia and PAOD, cholesterol-lowering with statin therapy significantly improved endothelium-independent vascular responses to SNP in skin microvessels. The application of the non-invasive techniques of iontophoresis and laser Doppler flowmetry may provide useful markers for the assessment of microvascular function in this group of patients.
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PMID:Lipid-lowering and skin vascular responses in patients with hypercholesterolaemia and peripheral arterial obstructive disease. 1061 27

A moderately elevated plasma total homocysteine (tHcy), whether measured during fasting or post-methionine load (PML), is increasingly being recognized as a risk factor for coronary artery diseases (CAD). However, etiologies for moderately elevated plasma tHcy, particularly with regard to the role of genetic influence on plasma tHcy levels, are still not well understood. In the current investigation, we studied 1025 individuals with respect to the effect of the 68-bp insertion (844ins68 variant) of the cystathionine beta-synthase (CBS) gene, the A(2756)G transition of the B(12)-dependent methionine synthase (MS) gene and the C(677)T transition of the methylenetetrahydrofolate reductase (MTHFR) gene on fasting and 4 h PML tHcy. Of these individuals, 153 (14.9%) were heterozygous for the 68-bp insertion, 329 (32.1%) were heterozygous for the G(2756) allele and 122 (11.9%) were homozygous for the C(677)T transition. Individuals heterozygous for the insertion had significantly lower PML increase in tHcy concentrations, while individuals homozygous for the A(2756)G transition had significantly lower fasting tHcy levels. A 2-way ANOVA showed that there was no interaction between the 844ins68 and the A(2756)G transition for either fasting tHcy or PML increase in tHcy, confirming the fact that the effect of these two genotypes on plasma tHcy levels are additive. The effects are opposite but additive with the C(677)50% of all individuals in this study carried polymorphic traits, which predisposed them to either higher or lower plasma tHcy concentrations, thus providing new evidence of the importance of genetic influences as determinants of tHcy levels.
Atherosclerosis 2000 Mar
PMID:Polygenic influence on plasma homocysteine: association of two prevalent mutations, the 844ins68 of cystathionine beta-synthase and A(2756)G of methionine synthase, with lowered plasma homocysteine levels. 1070 24

There is increasing evidence that the degree of postprandial lipaemia may be of importance in the development of atherosclerosis and IHD. Postprandial lipid, lipoprotein, glucose, insulin and non-esterified fatty acid (NEFA) concentrations were investigated in eleven healthy young males after randomized ingestion of meals containing rapeseed oil, sunflower oil or palm oil with or without a glucose drink. On six occasions each subject consumed consecutive meals (separated by 1.75 h) containing 70 g (15 g and 55 g respectively) of each oil. On one occasion with each oil 50 g glucose was taken with the first meal. One fasting and fifteen postprandial blood samples were taken over 9 h. There were no statistically significant differences in lipoprotein and apolipoprotein responses after rapeseed, sunflower and palm oils, whereas insulin responses were lower after sunflower oil than after rapeseed oil (ANOVA, P = 0.04). The NEFA and triacylglycerol concentrations at 1.5 h were reduced when 50 g glucose was taken with the first meal (ANOVA, P < 0.0001 and P < 0.05 respectively), regardless of meal fatty acid composition. In conclusion, the consumption of glucose with a mixed meal containing either rapeseed, sunflower or palm oil influenced the immediate triacylglycerol and NEFA responses compared with the same meal without glucose, whereas no significant effect on postprandial lipaemia after a subsequent meal was observed. The fatty acid composition of the meal did not significantly affect the lipid and lipoprotein responses, whereas an effect on insulin responses was observed.
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PMID:Postprandial lipoprotein, glucose and insulin responses after two consecutive meals containing rapeseed oil, sunflower oil or palm oil with or without glucose at the first meal. 1074 81

The oxidation of low-density lipoproteins (LDL) is considered a key event in the initiation of atherosclerosis. The aim of this study was to follow-up the biological marker of in vivo LDL oxidation (oxidatively modified LDL autoantibody titres) during long-term LDL-apheresis treatment. A patient suffering from severe combined hyperlipidaemia underwent LDL-apheresis biweekly and was followed for two years. The significant reduction of baseline total cholesterol (58%), total triglycerides (80%), LDL-cholesterol (48%), apoprotein B (50%) and apolipoprotein (a) (61%) may be considered as a good response to the treatment. The titre of autoantibodies (IgG) against oxidatively modified LDL (malondialdehyde-derived LDL) was followed throughout the study and showed dynamic changes. The measured values were multiple compared as mean+/-SD over each semester of apheresis application: I semester 70.0+/-8.3 U/ml, n = 12; II semester 58.0+/-13.8 U/ml, n = 12; III semester 37.6+/-6.0 U/ml, n=12; IV semester 34.3+/-7.0 U/ml, n = 12; ANOVA: I vs. II semester p<0.083, II vs. III semester p<0.00053, III vs. IV semester p<0.248. In parallel to the changes in this biochemical parameter, regression of numerous xanthomas was clinically observed. In spite of this, the presence of oxidised-LDL (oxLDL) antibodies was enhanced in comparison to antibody titre detected in a group of age-matched normolipaemic healthy controls (n = 15; 19.4+/-8.6; p<0.01). Classical lipoprotein parameters were correlated with the titre of autoantibodies against oxLDL and showed low correlation coefficients: total cholesterol vs. oxLDLab, r = 0.36; triglycerides vs. oxLDLab, r = 0.43; LDL cholesterol vs. oxLDLab, r = 0.14; HDL cholesterol vs. oxLDLab, r = -0.33; apo B vs. oxLDLab, r = 0.25; apo (a) vs. oxLDLab, r = -0.05. Our study showed an additional benefit of LDL-apheresis therapy. The production of autoantibodies against oxLDL was reduced during the treatment, indicating a lower level of the atherogenic antigen.
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PMID:Changes of autoantibodies against oxidatively modified low density lipoproteins during long-term LDL-apheresis. 1078 63


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