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

This study evaluated the effect of dietary cadmium (Cd) on atherosclerosis in the rabbit. Cholesterol was added to the diet to initiate and/or accelerate atherogenesis. Cd was added to the diet at two dose levels. Uptake of Cd was 55 micro gram/kg body weight (BW)/day at the low dose level and 1350 micrograms/ kg BW/day at the high dose level. Five groups of rabbits were fed five different diets for 9 months: (1) basal diet without additional constituents; (2) background diet, which was basal diet to which cholesterol had been added; (3) the low-dose level Cd diet, which was background diet to which 2 mg Cd/kg had been added; (4) high-dose level Cd diet, which was background diet to which 50 mg Cd/kg had been added; and (5) basal diet to which 50 mg Cd/kg had been added. Dietary cholesterol increased blood total leucocyte count, serum and liver total cholesterol concentrations, serum total bilirubin concentration, low-density lipoprotein vitamin E concentration and induction of atherosclerotic plaques in the aorta and coronary arteries. Cd in the diet increased liver and kidney Cd concentrations in a dose-dependent way, decreased prothrombin time and temporarily increased urea and creatinine clearances. Slight kidney damage was induced by Cd only in animals fed the high-dose level Cd diet (with or without cholesterol). Dietary Cd partly counteracted the dietary cholesterol-induced increases of serum and liver total cholesterol concentrations, and tended to reduce plaque formation in the aorta. Dietary Cd in rabbits fed cholesterol-containing diets influenced cholesterol metabolism and tended to decrease atherosclerosis in a dose-related fashion. This is in contrast with limited epidemiological human data. Dietary Cd also decreased serum ferritin concentration and increased serum transferrin concentration. Free iron concentration is associated with myocardial infarction in man and augments the development of atherosclerosis in rabbits. It is concluded that the observed reduction in atherogenesis is related to dietary Cd-induced changes in cholesterol metabolism, increased rheology of blood and/or, most likely, reduced free iron concentration.
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PMID:Cadmium and atherosclerosis in the rabbit: reduced atherogenesis by superseding of iron? 876 54

Oxidized low density lipoprotein (oxLDL) is known to be toxic to a variety of cell types, but relatively little is known about the toxic effects of oxLDL on vascular smooth muscle cells (SMC). We found that LDL oxidized by incubation with 5 microM cupric ions was toxic to cultured porcine SMC when administered at concentrations of 25 micrograms protein/ml and higher. The toxicity was demonstrated whether cells were proliferating or not, and was more evident in the presence of 0.4% lipoprotein-deficient serum than in 10%. Because of recent evidence that 7-ketocholesterol and 7-hydroxycholesterol are toxic species in copper-oxidized LDL, inhibition of 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase was hypothesized as a mechanism of toxicity. However, mevalonic acid, the product of this enzyme, failed to protect against the toxicity of either oxLDL or the pure oxysterols. Alpha-tocopherol, alpha-tocopherol acetate, probucol, butylated hydroxytoluene, and deferoxamine provided partial protection to SMC exposed to oxLDL. These results suggested a toxic role for newly initiated lipid peroxidation, either in cells or in media oxLDL. Cellular lipid peroxidation appeared more likely, since no further oxidation of media oxLDL was demonstrated in the presence or absence of antioxidants. Overall, the results suggest that toxicity of copper-oxidized LDL for SMC is multifactorial and differs from the previously described toxicity of iron-oxidized LDL for fibroblasts.
Atherosclerosis 1995 Dec
PMID:Toxicity of oxidized low density lipoproteins for vascular smooth muscle cells and partial protection by antioxidants. 877 Mar 18

The oxidative modification of low density lipoprotein (LDL) has been implicated as an early step in the formation of atheromatous lesions. In vitro studies suggest it to be accelerated, or even initiated, by transition metals such as iron or copper in combination with a reducing agent. Even if such metals have been demonstrated in atheroma gruels, their origin and precise localisation within human atheroma are presently unknown. In the initial part of this study we applied Pearl's method, energy dispersive X-ray microanalysis, and a modified Timm sulphide silver method (SSM) to demonstrate the occurrence of iron in early atherosclerotic lesions from a number of consecutive autopsy cases with evident, general atheromatosis. With the very sensitive SSM, but not with the other techniques, we found foam cells to contain heavy metals with a mainly lysosomal localization. On the basis of the hypothesis that such a lysosomal accumulation of iron might be due to erythrophagocytosis by migrating tissue-bound macrophages that later develop into foam cells, we designed an in vitro model system where human monocyte-derived macrophages were exposed to artificially aged, UV-exposed erythrocytes. The macrophages were then exposed to LDL in serum-and iron-free RPMI medium, occasionally in the presence of the potent iron-chelator desferrioxamine. The capacity of macrophages to oxidise LDL was much enhanced following erythrophagocytosis, and the process was shown to involve secretion of iron. Consequently, LDL oxidation was greatly inhibited by desferrioxamine. We conclude that iron may be exocytosed by macrophages that previously had their lysosomal apparatus enriched with iron, e.g. due to erythrophagocytosis. Oxidation of LDL may result in ensuing foam cell-formation secondary to scavenger-receptor mediated endocytosis by macrophages.
Atherosclerosis 1996 Jul
PMID:Iron in human atheroma and LDL oxidation by macrophages following erythrophagocytosis. 880 Apr 94

Modulation of the glutathione redox cycle may influence tumor necrosis factor-alpha (TNF)-mediated disturbances of endothelial integrity. To test this hypothesis, normal endothelial cells or cells with either increased or decreased glutathione levels were exposed to 100 ng (500 U) TNF/ml. Increased glutathione levels were achieved by exposure to 0.2 mM N-acetyl-L-cysteine (NAC) and decreased glutathione levels by exposure to 25 microM buthionine sulfoximine (BSO). Several components of the glutathione redox cycle as well as markers of endothelial integrity, such as cytoplasmic free calcium and transendothelial albumin transfer, were measured in the treated cells. Exposure to TNF for 3 and 6 h decreased total glutathione levels, which was followed by an increase at later time points. Moreover, treatment with TNF resulted in an increase in the ratio of oxidized to reduced glutathione, intracellular free calcium, albumin transfer across endothelial monolayers and lipid hydroperoxides. However, an increase in lipid hydroperoxides was seen only when endothelial cell cultures were supplemented with iron. BSO treatment increased susceptibility of endothelial cells to TNF-mediated metabolic disturbances. On the other hand, NAC partially protected against TNF-induced injury to endothelial monolayers. Our results demonstrate the important role of the glutathione redox cycle in TNF-mediated disturbances of the vascular endothelium and indicate that modulation of glutathione levels may potentiate the injurious effects of this inflammatory cytokine.
Atherosclerosis 1995 Oct
PMID:Role of glutathione redox cycle in TNF-alpha-mediated endothelial cell dysfunction. 880 63

The oxidative modification of low density lipoprotein (LDL) may play a role in the pathogenesis of atherosclerosis. Furthermore, evidence of oxidized LDL (ox-LDL) has been found in vivo. Supplementation of some animal models with antioxidants has been shown to retard the formation of aortic atherosclerosis. Ascorbate (vitamin C) is a highly potent aqueous-phase antioxidant in plasma, which has been shown in vitro to retard LDL oxidation. Cigarette smokers have reduced concentrations of ascorbate in their plasma, and their LDL may be more prone to oxidation. Hence, the objective of the present study was to examine the effect of ascorbate depletion and supplementation on the propensity of LDL to oxidize in smokers in a 6-week study. Nineteen healthy smokers followed a low ascorbate diet (< or = 30 mg/day) for 2 weeks, then were randomly assigned to receive placebo or 1000 mg ascorbate per day for 4 weeks. Blood was taken at 0 and 4 weeks of supplementation for study of LDL oxidative susceptibility. LDL was oxidized with 5 mumol/l copper. The ascorbate-supplemented group had significant increases in plasma ascorbate. The placebo group showed no change in the time course of LDL oxidation between 0 and 4 weeks. However, the ascorbate-supplemented group has a significant reduction in LDL oxidative susceptibility as measured by thiobarbituric acid-reactive substances (TBARS) and the formation of conjugated dienes. The ascorbate-supplemented group demonstrated significantly increased lag phase and decreased oxidation rate at 4 weeks compared to 0 weeks. No changes were found in the placebo group. The ascorbate-supplemented group showed no biochemical signs consistent with increased body iron stores. Supplementation of otherwise healthy smokers for 4 weeks with 1000 mg ascorbate per day resulted in increased plasma ascorbate and reduced LDL oxidative susceptibility.
Atherosclerosis 1996 Jan 26
PMID:Effect of ascorbate supplementation on low density lipoprotein oxidation in smokers. 880 91

The roles of iron and other trace metals in the aetiology of heart and brain diseases has been a subject of keen research because of the ability of metal ions to participate in reactions involving free radicals, which have been implicated in many of these diseases. Unstained freeze dried tissue sections from the aorta of New Zealand white rabbits fed with a 1% cholesterol diet for 12 weeks were scanned with a 2 MeV proton beam using the National University of Singapore nuclear microscope facility. Results from 6 test and 4 control rabbits show that there is an average of seven-fold increase in iron and an average of nearly two-fold increase in phosphorus in the atherosclerotic lesion compared with healthy tissue. The increase in iron adds weight to the hypothesis that iron-catalyzed free radical reactions may be associated with the development of atherosclerosis. A depletion of other elements analyzed was seen in the lesion. Elemental mapping also showed the occurrence of granules rich in sodium, chlorine and potassium at the interface between lesioned and non-lesioned tissue.
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PMID:Elemental changes in atherosclerotic lesions using nuclear microscopy. 883 71

Oxidized low density lipoprotein (LDL) may play a significant role in atherosclerosis. We have investigated the effect of pH on the oxidation of LDL by iron or copper. When LDL was oxidized by iron in the presence of cysteine in either Hanks' balanced salt solution (HBSS) or Ham's F-10 medium, an acidic pH greatly decreased the lag period and increased the rate of formation of hydroperoxides and thiobarbituric acid-reactive substances (TBARS), and increased its uptake by macrophages. There was a dose-dependent increase of LDL oxidation at acidic pH in the presence of increasing concentrations of cysteine. When LDL was oxidized by copper in HBSS, an acidic pH increased the lag phase before the rapid formation of conjugated dienes, hydroperoxides, and TBARS, but increased its uptake by macrophages. Similar results were obtained using Ham's F-10 medium. Cysteine (100 microM) inhibited the modification of LDL by copper in HBSS at both pH 7.4 and 5.5 As atherosclerotic lesions may be acidic, these observations may help to explain why LDL oxidation occurs locally at these sites.
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PMID:Oxidation of low density lipoprotein by iron or copper at acidic pH. 884 77

A mortality cohort study was carried out on 11,224 men with pneumoconiosis diagnosed during the period 1970-1985. The cohort was selected from among subjects entered into the National Register of Occupational Diseases and included 7,065 coal miners, 924 employees of underground work enterprises, 1,796 workers of the metallurgical industry and iron and nonferrous foundries, as well as 1,439 refractory materials, china, ceramics, and quarry workers. The cohort was traced up to the end of 1991. The mortality of all groups enrolled in the study, as compared with that of general male population of Poland, showed a statistically significant excess of overall mortality (SMRs ranging from 105; 95% confidence interval [CI]: 100-110 to 136; CI: 121-153) as well as a great excess of deaths from diseases of the respiratory system (SMRs from 383; 95% CI: 345-424 to 588; 95% CI: 457-744). In workers of the metallurgical industry, foundries, and those from refractory materials, china, and ceramics manufacturing plants as well as quarries, a statistically significant excess of deaths from infectious diseases (mostly tuberculosis) was found (SMRs: 503; 95% CI: 364-677 and 286; 95% CI: 177-437, respectively). Mortality from lung cancer was significantly elevated only in the group of metallurgical industry and iron and nonferrous foundry workers (SMR: 159; 95% CI: 124-201). In the remaining subcohorts, no significant excess of deaths from lung cancer was noted. The study does not support the hypothesis on the role of exposure to crystalline silica in the induction of lung cancer. Significantly lower mortality was seen for diseases of the circulatory system (SMR: 89; 95% CI: 82-96), hypertensive disease (SMR: 63; 95% CI: 38-98), cerebrovascular disease (SMR: 79; 95% CI: 62-99), atherosclerosis (SMR: 79; 95% CI: 66-93), and injuries and poisonings (SMR: 50; 95% CI: 38-64) in coal miners. In addition, lower mortality was noted for cerebrovascular disease (SMR: 56; 95% CI: 32-91) and injuries and poisonings (SMR: 34; 95% CI: 17-61) in metallurgical industry and iron and nonferrous foundry workers.
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PMID:Mortality among different occupational groups of workers with pneumoconiosis: results from a register-based cohort study. 891 18

It is postulated that cell injury activates "dormant" enzymes to produce lipid hydroperoxides. In a first step, membrane lipids are cleaved by esterases. The unsaturated fatty acids thus produced are converted in a second step by lipoxygenases to lipid hydroperoxides (LOOHs). In a third, nonenzymic step, these LOOHs, together with dienoic hydroxy fatty acids produced by enzymic reduction of LOOHs, react with a second oxygen molecule to generate dihydroperoxy-fatty acids and hydroxy-hydroperoxy-fatty acids, which are degraded to alpha-hydroxyladehydic compounds. This last reaction requires production of LO'-radicals by iron ions that also are generated as a result of cell damage. In addition, alpha-hydroxyaldehydes are produced by hydrolysis of plasmalogen epoxides, which are generated by oxidation of plasmalogens with LOO' or by action of epoxidases. We hypothize that alpha-hydroxyaldehydes act as second messengers. The release of lipoxygenase and the consequent lipid hydroperoxidation is postulated to occur in massive cell damage (e.g., myocardial infarction), in chronic diseases such as rheumatism, diabetes and atherosclerosis, in aging, and in control of cell proliferation.
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PMID:Enzymic lipid peroxidation--a consequence of cell injury? 893 85

Women experience only 30-50% of the coronary heart disease (CHD) incidence and mortality of age-matched men. Since oxidation of low-density lipoprotein (LDL) cholesterol is important in atherosclerosis, and oxidation is catalyzed by iron, it has been hypothesized that the lower iron stores of women reduce their risk of CHD through lessened lipid peroxide. The biochemistry of oxidation is well described in the literature and involves iron as a catalyst in the formation of powerful free radicals which subsequently modify LDL cholesterol. Chelating iron with desferrioxamine stops oxidation. Iron is present in atherosclerotic gruel and this gruel stimulates lipid peroxidation. Serum deficient in iron has minimal oxidative capacity which increases with iron repletion. At least seven epidemiologic studies have found a positive association between CHD and various indicators of body iron. Conversely 18 epidemiologic studies have found a negative or no association. While biochemically appealing, the iron hypothesis remains unproven.
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PMID:The iron hypothesis--does iron cause atherosclerosis? 895 95


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