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)

Oxidative modification of low density lipoprotein (LDL) is supposed to be important in atherogenesis. Recently it was shown that subjects with coronary atherosclerosis have an increased susceptibility of their LDL to copper-induced oxidation. We investigated if patients with intermittent claudication (IC) might have an increased susceptibility of LDL to copper-induced oxidation. Fifty-eight males were randomly selected from an epidemiological study of IC, 29 with IC and 29 healthy controls matched for age, sex and smoking habits. All subjects performed a standard exercise test to confirm or exclude peripheral atherosclerosis. Claudicants had a lag phase of 99.7 +/- 14.8 minutes (mean +/- SD) and in healthy controls it was 104.6 +/- 12.9 minutes. The difference between the groups was not significant and neither was there any association between lag phase and degree of peripheral atherosclerosis in IC. Lag phase showed a positive and significant correlation to the plasma concentration of high density lipoprotein-2 (HDL2-) cholesterol. The correlation for the whole group was r = 0.41, p < 0.01. We conclude that the susceptibility of LDL to copper-oxidation does not discriminate between claudicants and healthy controls. The results also suggest that high plasma concentrations of HDL2-cholesterol may have a protective effect on LDL against oxidation.
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PMID:Copper-induced low density lipoprotein oxidation is not a risk discriminator for intermittent claudication. 865 13

Vitamin E has been postulated to be antiatherogenic because of its antioxidative potency. However, intervention studies published to date have yielded conflicting results. To assess the antiatherogenic effect of vitamin E, two groups of 10 Watanabe heritable hyperlipidemic (WHHL) rabbits each were fed chow pellets containing D-alpha-tocopherol-acetate at either 40 mg/kg (control group) or 1000 mg/kg (vitamin E group) for 28 weeks. Plasma vitamin E levels in the vitamin E group increased five-fold over those controls (475.5 mumol/l vs. 95.9 mumol/l). The average total plasma cholesterol during the treatment period was not significantly affected by vitamin E (control, 950 +/- 113 mg/dl; vitamin E, 884 +/- 90 mg/dl). Vitamin E treatment had no significant effects on body weights, lipoprotein profiles, or HDL levels. The protection of plasma LDL against oxidation was determined by ex vivo by measuring the lag time in the formation of conjugated dienes in a standardized Cu22+(-)containing system. Lag time in the vitamin E-treated group increased four-fold over that in controls (404 vs. 123 min). The extent of atherosclerosis determined at the end of the study was not significantly different in the two groups (control group, 59.2 +/- 6.0%; vitamin E group, 50.6 +/- 6.2%, P = 0.33). Analysis of the correlation between vitamin E levels and extent of lesions also failed to indicate an antiatherosclerotic effect of vitamin E treatment. We previously reported that an analogue of probucol that provided antioxidative protection similar to that provided by vitamin E failed to prevent atherogenesis in WHHL-rabbits. In contrast probucol conveyed a much greater degree of antioxidant protection and effectively reduced atherosclerosis in rabbits. The results of the present study therefore support the hypothesis that a threshold level of antioxidative protection of LDL may be required to inhibit atherosclerosis.
Atherosclerosis 1995 Oct
PMID:Effect of vitamin E on atherogenesis in LDL receptor-deficient rabbits. 880 67

Copper-induced plasma lipoprotein oxidation resistance has usually been determined in separated low density lipoprotein (LDL) fractions, that do not contain water-soluble antioxidants present in blood plasma. The aim of this study was to find the main determinants of the measurements of copper-induced lipid oxidation resistance (lag time) in whole serum and plasma total peroxyl radical trapping capacity (TRAP) in a population sample of smoking (n = 25) or non-smoking (n = 26) middle aged men at high risk of cardiovascular diseases. Smokers had significantly lower plasma ascorbic acid values, but only slightly lower alpha-tocopherol, beta-carotene and serum urate values than non-smokers. Plasma ascorbic acid concentration explained 23.5% of the lag time variation (standardized regression coefficient beta = 0.48; P = 0.004) in smokers and 5.6% in non-smokers. Serum urate concentration was the strongest determinant of lag time in non-smokers (beta = 0.64, P < 0.001). In addition, serum albumin, lipid standardized alpha-tocopherol and serum high density lipoprotein (HDL) cholesterol entered the multivariate regression mode for lag time. For plasma TRAP, only urate and ascorbic acid entered the multivariate regression model. Lag times in serum and in isolated very low density lipoprotein (VLDL) and LDL fraction did not correlate, but the maximal rate of these reactions correlated significantly. These results confirm that lipid peroxidation resistance in serum or plasma are associated with ascorbic acid, urate, alpha-tocopherol, albumin and HDL concentrations. The measurement of lipid oxidation resistance in whole serum might be more physiological than in isolated lipoprotein fraction, as the effects of water-soluble antioxidants are not artificially removed.
Atherosclerosis 1997 Apr
PMID:Ascorbate and urate are the strongest determinants of plasma antioxidative capacity and serum lipid resistance to oxidation in Finnish men. 912 68

It has previously been demonstrated that vascular dendritic cells reside in the arterial intima and are involved in human atherogenesis. During the present ultrastructural examination of aortic atherosclerotic lesions, pentalaminal structures, similar to Birbeck granules which uniquely present in Langerhans cells, were found in the cytoplasm of vascular dendritic cells and the formation of these Birbeck granule-like structures from dense granules was identified. To find out how Birbeck granule-like structures might relate to Birbeck granules of Langerhans cells, we used Lag-antibody which specifically stains Birbeck granules and Birbeck granule-associated structures in Langerhans cells. Lag-positive cells were found in the aortic wall. Our observations suggest a close relationship between vascular dendritic cells and Langerhans cells and this may imply that mechanisms of antigen presentation known for Langerhans cells might be similar to those involved in atherosclerosis.
Atherosclerosis 1997 Sep
PMID:Formation of Birbeck granule-like structures in vascular dendritic cells in human atherosclerotic aorta. Lag-antibody to epidermal Langerhans cells recognizes cells in the aortic wall. 1048 5

Low-density lipoprotein (LDL) oxidation is central to the pathogenesis of atherosclerosis. We have shown previously that the herbal mixtures Maharishi Amrit Kalash-4 (MAK-4) and Maharishi Amrit Kalash-5 (MAK-5) inhibit LDL oxidation induced by cupric ions (Cu+2) and endothelial cells in vitro and that MAK-4 reduces atherosclerosis in Watanabe heritable hyperlipidemic rabbits that were fed this herbal mixture. This study evaluates the antioxidant activity of MAK-4 and MAK-5 in vivo. Ten hyperlipidemic patients prescribed stable hypolipidemic therapy were treated with MAK-4 and MAK-5 for 18 weeks. Plasma lipoprotein, plasma lipid peroxide, and LDL oxidation studies were performed every 6 weeks. Apolipoprotein A, apolipoprotein B, and lipoprotein (a) levels were measured at baseline and 18 weeks. After 12 weeks of treatment with MAK-4 and MAK-5, a time-dependent increase in the lag phase and delay in the propagation phase of oxidation of LDL by Cu+2 and endothelial cells was seen. Lag phases at baseline and after 6, 12, and 18 weeks of MAK-4 and MAK-5 ingestion were 6.66 hours +/- 0.19 (mean +/- standard error of mean), 6.77 hours +/- 0.31, 7.22 hours +/- 0.24, and 18.00 hours +/- 0.73, respectively, for Cu(+2)-catalyzed LDL oxidation. Lag phases were 14.89 hours +/- 0.77, 13.33 hours +/- 0.50, 20.22 hours +/- 0.76, and 20.00 hours +/- 0.79, respectively, for endothelial cell-induced LDL oxidation. The levels of plasma lipid peroxide did not change significantly. No significant changes were seen in the plasma lipoproteins and the levels of apolipoprotein A, apolipoprotein B, and lipoprotein (a). The results show that MAK-4 and MAK-5 inhibit LDL oxidation in patients with hyperlipidemia. Therefore, MAK-4 and MAK-5 may be useful in the prevention and treatment of atherosclerosis.
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PMID:Inhibition of low-density lipoprotein oxidation by oral herbal mixtures Maharishi Amrit Kalash-4 and Maharishi Amrit Kalash-5 in hyperlipidemic patients. 936 32

Six, healthy, male volunteers aged 19-48 years received a 4-h infusion of a triacylgycerol emulsion (Intralipid 10%) after an overnight fast. Plasma triacylglycerol (TAG) and low-density lipoprotein (LDL) -TAG, -protein and -phospholipid concentrations all rose significantly during the course of the infusion and remained elevated 90 min after its end. The weight/weight ratio of LDL-TAG to -protein also increased significantly (from 0.43+/-0.14 to 0.79+/-0.30 at 4 h and 0.63+/-0.31 90 min later), indicating TAG-enrichment of LDL particles. There were no significant changes in LDL particle density. Susceptibility of LDL to copper-induced oxidation, as measured by the lag time for conjugated diene formation, was less at the end of and 90 min after the end of the infusion than in the fasting state (59.3+/-16.5, 47.4+/-17.4 and 34.8+/-19.6 min, respectively). Lag time was positively correlated with LDL TAG in the fasting state (rS=0.900, P < 0.0001) and the correlation continued with the post-infusion TAG-enriched LDL (rs=0.886, P < 0.05). Acute hypertriglyceridaemia induced by infusion of Intralipid therefore causes TAG-enrichment and a decrease in the susceptibility to oxidation of LDL. TAG-enrichment of LDL may lead to subsequent potentially atherogenic changes in LDL following TAG hydrolysis.
Atherosclerosis 1998 Mar
PMID:Effect of infusion of a triacylglycerol emulsion on low-density lipoprotein composition and oxidizability. 956 43

Body iron status has been implicated in atherosclerotic cardiovascular disease. The main hypothesis was that high iron status was associated with increased oxidation of LDL. The associations of serum ferritin (a marker of iron status) and dietary iron intake with the susceptibility of LDL to in vitro oxidation (lag phase) and autoantibodies against MDA-modified LDL (two markers of oxidation stress) were examined among 281 men and 192 women with a mean age of 59 years (S.D. = 5) who participated in the Atherosclerosis Risk in Communities (ARIC) Study visit 2 in 1990 through 1992. Lag phase duration and the autoantibodies against MDA-modified LDL were weakly correlated with each other (r = 0.19, P = 0.001 in men; r = 0.15, P = 0.03 in women). In linear regression analysis adjusting for age, field center, blood storage time, and carotid atherosclerosis case-control status, there was no association between ferritin level and the lag-phase, or between ferritin level and autoantibodies against MDA-modified LDL in either sex. Further adjustment for traditional cardiovascular risk factors (smoking, vitamin supplement use, body mass index, LDL cholesterol, hypertension and diabetes) did not alter these null results. Ferritin was significantly and positively correlated with body mass index in both sexes (r = 0.21 among men and r = 0.22 among women) and with the waist-to-hip ratio among women (r = 0.26). In addition, among women, ferritin was positively correlated with orosomucoid (r = 0.24) and with sialic acid (r = 0.19). Dietary iron was not associated with the parameters of LDL oxidation or with ferritin level. These findings do not support a role of body iron stores in promoting oxidation of LDL.
Atherosclerosis 1998 Jul
PMID:Lack of association between ferritin level and measures of LDL oxidation: the ARIC study. Atherosclerosis Risk in Communities. 969 7

One of the earliest steps of atherosclerotic plaque formation is an increase of circulating apolipoprotein B-containing lipoproteins which, after infiltrating the subendothelial space, undergo oxidative modification. Fenofibrate is an effective cholesterol- and triglyceride-lowering agent which has been shown to be beneficial in the treatment of atherosclerosis. Vitamin E, or alpha-tocopherol, is a powerful antioxidant which has been shown in a variety of studies to prevent lipoprotein peroxidation. The purpose of the present study was to investigate the effect of fenofibrate treatment, either alone or in combination with alpha-tocopherol, in reducing the susceptibility of lipoproteins to oxidative modification. Rats fed a normal diet were treated for up to 27 d with fenofibrate, either alone or in combination with equimolar doses of alpha-tocopherol. Combined VLDL (very low density lipoproteins) and LDL (low density lipoproteins) isolated after fenofibrate treatment were more resistant to copper-mediated oxidation, as assessed by conjugated diene formation. Lag time was prolonged up to 3.2-fold, while the maximal rate of diene production was significantly decreased by up to 2.2-fold. Treatment of rats with alpha-tocopherol alone at the selected dose had no significant effect on lag time, while the propagation rate was slightly decreased. Coadministration of fenofibrate with alpha-tocopherol prolonged the lag phase to a greater extent than fenofibrate alone, showing a synergistic interaction between the two compounds. Finally, the combination of fenofibrate and alpha-tocopherol was significantly more effective in modifying lipoprotein oxidation parameters than what was observed with alpha-tocopherol and bezafibrate or gemfibrozil. Thus, in addition to its well-established effects on lipoprotein concentrations and atherogenic parameters, fenofibrate reduces the susceptibility of VLDL and LDL to oxidative modification and exerts its action synergistically with alpha-tocopherol.
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PMID:Fenofibrate protects lipoproteins from lipid peroxidation: synergistic interaction with alpha-tocopherol. 1038 Jan 22

Oxidized low density lipoprotein (LDL) has a major impact in the development of atherosclerosis. Risk for oxidative modification of LDL is usually determined indirectly by measuring the capability of LDL to resist radical insult. We compared three different methods quantifying the antioxidative capacity of LDL ex vivo in dyslipidemic patients with coronary heart disease. Plasma samples were obtained from two double-blinded cross-over trials. The duration of all interventions (placebo, lovastatin 60 mg/day, RRR-alpha-tocopherol 300 mg/day and lovastatin + RRR-alpha-tocopherol combined) was 6 weeks. The total radical capturing capacity of LDL (TRAP) in plasma was determined using 2,2-azo-bis(2,4-dimethyl-valeronitrile) (AMVN) -induced oxidation, and measuring the extinction time of chemiluminescence. TRAP was compared to the variables characterizing formation of conjugated dienes in copper-induced oxidation. Also the initial concentrations and consumption times of reduced alpha-tocopherol (alpha-TOH) and ubiquinol in AMVN-induced oxidation were determined. Repeatability of TRAP was comparable to that of the lag time in conjugated diene formation. Coefficient of variation within TRAP assay was 4.4% and between TRAP assays 5.9%. Tocopherol supplementation produced statistically significant changes in all antioxidant variables except those related to LDL ubiquinol. TRAP increased by 57%, the lag time in conjugated diene formation by 34% and consumption time of alpha-TOH by 88%. When data of all interventions were included in the analyses, TRAP correlated with the lag time (r = 0.75, p < 10(-6)), with LDL alpha-TOH (r = 0.50, p < 0.001) and with the consumption time of alpha-TOH (r = 0.58, p < 0.0001). In the baseline data, the associations between different antioxidant variables were weaker. TRAP correlated with the lag time (r = 0.55, p < 0.001) and alpha-TOH consumption time (r = 0.48, p < 0.05), and inversely with apolipoprotein Al (r = -0.51, p < 0.05). Lag time at the baseline did not correlate with ubiquinol or tocopherol parameters, or with any plasma lipid or lipoprotein levels analyzed. Lovastatin treatment did not significantly affect the antioxidant capacity of LDL. In conclusion, TRAP reflects slightly different properties of LDL compared to the lag time. Thus, LDL TRAP assay may complement the other methods used to quantify the antioxidant capacity of LDL. However, TRAP and the lag time react similarly to vitamin E supplementation.
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PMID:Comparison of LDL trap assay to other tests of antioxidant capacity; effect of vitamin E and lovastatin treatment. 1120 90

Probucol, an antioxidative and hypolipidemic agent, has been postulated to increase reverse cholesterol transport by enhancing cholesteryl ester transfer protein (CETP) activity. However, its clinical implication in CETP deficient patients has not been fully defined. To characterize the effects of probucol in the absence of CETP, we evaluated the changes in lipid profile, lipid peroxidation, and paraoxonase 1 (PON1) activity in two complete CETP deficient patients, caused by treatment with probucol. When the patients were not receiving probucol, low-density lipoprotein (LDL) particles were smaller and high-density lipoprotein (HDL) particles were larger in these patients than in controls. Treatment with probucol (500 mg/day) resulted in the decrease in the levels of HDL-C and apolipoprotein (apo) A-I up to 22%. The size of HDL particles became smaller. LDL cholesterol concentration did not change in one patient, while it decreased by 47% in the other. PON1 activity/HDL-C, which was about 40% lower in the patients before treatment than in controls with the matching PON1 genotype, increased by 30% during the treatment. Lag time for LDL and HDL in both cases became prolonged more than 1.8 times after administration of probucol. This study demonstrated for the first time that probucol reduces HDL-C even in humans with complete CETP deficiency. Probucol treatment in these patients was also associated with protection of lipoproteins against oxidative stress, suggesting a clinical benefit of this drug even in such a state.
Atherosclerosis 2003 Nov
PMID:Modulation of HDL metabolism by probucol in complete cholesteryl ester transfer protein deficiency. 1464 15


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