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)

Cultured smooth muscle cells from pig aortas were incubated with low density lipoproteins (LDL) and chloroquine for up to 5 days, as an in vitro model for lipid accumulation in atherosclerosis. Cells incubated with LDL alone had a normal morphology, except that some cells contained large lipid droplets. The activities of acid phosphatase, catalase and malate dehydrogenase were increased in homogenates prepared from these cells. Cells incubated with chloroquine alone developed large autophagic vacuoles. The activities of the three acid hydrolases, acid phosphatase, N-acetyl-beta-glucosaminidase and beta-glucuronidase, were decreased, as was the proteolytic activity of the cell homogenates at acid pH toward 125I-labelled LDL. There was, however, a transient increase in the activity of malate dehydrogenase. Chloroquine by itself was toxic to the cells, but LDL protected against this toxic effect. Cells incubated with LDL and chloroquine together developed both autophagic vacuoles and large lipid droplets. The cholesteryl ester content of the cells was increased many-fold and the non-esterified cholesterol content was increased to a lesser extent. The above four acid hydrolase activities were decreased, as was the activity of catalase, whereas the activities of lactate dehydrogenase and malate dehydrogenase were increased.
Atherosclerosis 1982 Sep
PMID:Lipid accumulation in arterial smooth muscle cells in culture. Morphological and biochemical changes caused by low density lipoproteins and chloroquine. 715 Mar 93

Evidence is accumulating that most of the degenerative diseases that afflict humanity have their origin in deleterious free radical reactions. These diseases include atherosclerosis, cancer, inflammatory joint disease, asthma, diabetes, senile dementia and degenerative eye disease. The process of biological ageing might also have a free radical basis. Most free radical damage to cells involves oxygen free radicals or, more generally, activated oxygen species (AOS) which include non-radical species such as singlet oxygen and hydrogen peroxide as well as free radicals. The AOS can damage genetic material, cause lipid peroxidation in cell membranes, and inactivate membrane-bound enzymes. Humans are well endowed with antioxidant defences against AOS; these antioxidants, or free radical scavengers, include ascorbic acid (vitamin C), alpha-tocopherol (vitamin E), beta-carotene, coenzyme Q10, enzymes such as catalase and superoxide dismutase, and trace elements including selenium and zinc. The eye is an organ with intense AOS activity, and it requires high levels of antioxidants to protect its unsaturated fatty acids. The human species is not genetically adapted to survive past middle age, and it appears that antioxidant supplementation of our diet is needed to ensure a more healthy elderly population.
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PMID:The role of free radicals in disease. 761 52

Methionine is converted by the transmethylation/transsulfuration pathway to homocysteine which may exert atherogenic effects by several mechanisms, including lipid peroxidation. Therefore, the excessive dietary methionine may induce the development of atherosclerosis. To test this hypothesis, plasma and aortic thiobarbituric acid reactive substances (TBARS), as well as activities of aortic and erythrocyte superoxide dismutase (SOD), catalase and selenium-dependent glutathione peroxidase (GPX) were measured in rabbits fed a diet enriched with 0.3% methionine for 6 or 9 months. Histological examinations of aortas also were performed. Feeding rabbits a methionine-enriched diet for 6 or 9 months resulted in significant increases in plasma and aortic TBARS levels and aortic antioxidant enzyme activities. However, a decrease in plasma antioxidant activity (AOA) was observed. In erythrocytes, SOD activity increased, catalase remained normal and GPX decreased in the treated animals. Histological examination of aortas showed typical atherosclerotic changes, such as intimal thickening, deposition of cholesterol, and calcification in methionine-fed rabbits. These results confirm that high-methionine diet may induce atherosclerosis in rabbits and indicate disturbances in lipid peroxidation and antioxidant processes as possible mechanisms of its atherogenic influence.
Atherosclerosis 1995 Jun
PMID:Increased lipid peroxidation as a mechanism of methionine-induced atherosclerosis in rabbits. 766 80

Selected parameters of lipid metabolism (cholesterol, HDL cholesterol, LDL cholesterol, atherogenic index, triacylglycerols, vitamin C, vitamin E, vitamin E/cholesterol, plasma fatty acid profile) and pro-oxidative/anti-oxidative parameters (conjugated dienes of fatty acids, activity of catalase and glutathione peroxidase) were estimated in blood of 59 healthy vegetarians aged 19-30 years. When compared to non-vegetarians, no incidence of obesity, low levels of cholesterol, LDL cholesterol, atherogenic index or triacylglycerols, HDL cholesterol levels on the margin of 1.4 mmol/l (boundary level between standard and reduced risk) as well as a higher plasma content of polyunsaturated fatty acids and a higher 18:2/18:1 ratio were all favourable consequences of vegetarianism with respect to atherosclerosis prevention. These factors are completed by higher levels of protective compounds with antisclerotic activity (vitamin C, vitamin E/cholesterol--protecting LDL from lipoperoxidation) as well as by beneficial pro-oxidative/anti-oxidative parameters (low values of conjugated dienes, significantly higher activity of catalase, higher level of vitamin C).
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PMID:Selected parameters of lipid metabolism in young vegetarians. 770 61

The authors subdued 183 vegetarians to examination, the aim of which was to judge the state of health and nutrition of the vegetarian population. The examined group was composed of people with their age ranging from 19-60 years, out of which 102 were of younger (19-39 years) and 81 were of older age. Their average period of vegetarian food consumption was 4.2 years. One third of men and a half of women were lacto-vegetarians, the rest were lacto-ovo-vegetarians. The results were compared with 160 nonvegetarians (64 of younger and 96 of older age). The detected values of lipid parameters were evaluated as favourable for vegetarians (low values of cholesterol, triacylglycerols, atherogenic index, LDL-cholesterol, the share of HDL-cholesterol was 28-33% (vs 24-26% in nonvegetarians) with values converging to 1.4 mmol.l-1--i.e. reduced risk). Additional favourable factors in prevention of atherosclerosis include the absence of obesity in vegetarians and values of antisclerotic active substances in blood (high values of vitamin C, in comparison with nonvegetarians a significantly higher molar ratio of vitamin E/cholesterol and vitamin E/triacylglycerols--more effective protection against peroxidation of lipids). Vegetarian mode of food consumption may be favourably evaluated regarding prooxidative-antioxidative parameters which play an important role in the process of atherogenesis, and carcinogenesis. Significantly lower values of conjugated dienes in plasma of vegetarians and vice versa high values of antioxidant substances (vitamin C, vitamin E/lipid components, catalase activity) were detected. A more pronounced system of detoxication in vegetarians is important due to a possible risk of an increased intake of xenogenous substances. (Tab. 3, Ref. 27.)
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PMID:[Lipid and pro-oxidative and antioxidative parameters in the blood of vegetarians]. 855 57

The present study demonstrates for the first time that iron ions can induce lipid peroxidation in intact macrophages without causing cell death. Macrophage lipid peroxidation increases cell-mediated oxidation of LDL, enhances the release of interleukin 1 and inhibits the release of apolipoprotein E from the macrophages. When cultured macrophages were exposed to ferrous ions (50 microM FeSO4) for 4 h at 37 degrees C, cellular lipid peroxidation (measured by analyses of malondialdehyde (MDA), conjugated dienes (CD), and lipid peroxides (PD)) increased 2-4-fold in comparison with non-treated cells. This process was iron-dose dependent, reached its maximum after 4 h of incubation, and was accompanied by 68% and 53% reductions in the content of the cellular linoleic (18:2), and arachidonic acid (20:4), respectively, and by 29% and 36% reductions of cellular vitamin E and vitamin A, respectively. Cell viability (measured by trypan blue exclusion, by [3H]thymidine incorporation into DNA, by analysis of the release of lactate dehydrogenase (LDH) or [3H]adenine), and cell morphology (studied by scanning electron microscopy) were not significantly affected by the iron-induced oxidative stress. Manitol and dimethylthiourea (DMTU), but not catalase or superoxide dismutase (SOD), significantly inhibited iron-induced cellular lipid peroxide formation, suggesting that hydroxyl radical, but not superoxides or hydrogen peroxides, mediated the iron-induced cellular lipid peroxidation. Incubation of LDL (0.2 mg of protein/ml) with oxidized macrophages resulted in LDL lipids peroxidation, as evidenced by an 8-fold increase in the LDL associated MDA in comparison with LDL that was incubated under similar conditions with non-oxidized macrophages. Furthermore, oxidation of LDL by oxidized macrophages in the presence of copper ions (10 microM CuSO4) was 2-fold higher in comparison with oxidation of LDL by non-oxidized macrophages. The release of apolipoprotein E from oxidized macrophages decreased by 50%, whereas macrophage release of beta-glucuronidase and of interleukin-1 beta increased by 83% and by a factor of 6, respectively. This study demonstrates for the first time that iron ions induce oxidation of the cellular polyunsaturated fatty acids in intact macrophages and that this cellular lipid peroxidation can subsequently induce LDL oxidation.
Atherosclerosis 1994 Nov
PMID:Iron induces lipid peroxidation in cultured macrophages, increases their ability to oxidatively modify LDL, and affects their secretory properties. 784 Aug 15

Vascular complications such as atheroma, hypertension and macroangiopathy are the leading causes of morbidity and mortality in diabetic patients. Epidemiological and clinical data linking hyperinsulinaemia to both hypertension and atherosclerosis are inconsistent. Hyperglycaemia is the distinguishing feature of diabetes and it seems a likely candidate for the poor cardiovascular outlook of diabetic patients. High blood glucose levels cause selective impairment of endothelium-dependent relaxation and delay cell replication time of cultured human endothelial cells. These effects of hyperglycaemia are reversed by a number of antioxidants, including superoxide dismutase, catalase and glutathione. Impaired endothelium-dependent vasodilation has been reported both in Type 1 and Type 2 diabetic patient. The evidence for a role of oxygen-derived free radicals in the pathogenesis of vascular diabetic complications can be summarized as follows: 1) glucose can auto-oxidize generating oxygen derived free radicals; 2) elevated levels of oxygen derived free radicals are found in red blood cells, plasma and retina of diabetic animals and patients, and correlate with metabolic control; 3) endogenous antioxidants are all decreased in diabetic tissues and blood; and 4) treatment with different antioxidants may improve many of the metabolic abnormalities reported to occur in diabetic patients. The use of antioxidants to reduce the risk of coronary heart disease in diabetes should await the results of randomized trials with these drugs in the primary and secondary prevention of coronary disease.
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PMID:Medical hypothesis: cardiovascular complications of diabetes mellitus-from glucose to insulin and back. 785 91

Cell-mediated oxidative modification of human low density lipoprotein (LDL), most likely an important early step in atherosclerosis, requires redox active metal ions such as copper or iron. We have previously shown that iron-dependent, in contrast to copper-dependent, oxidative modification of LDL requires superoxide, a physiological reductant. In the present study, we sought to explain these discrepant results. LDL was incubated at 37 degrees C with Cu2+ (10 microM) and bathocuproine (BC, 360 microM), an indicator molecule which specifically complexes Cu+, but not Cu2+. In a time- and concentration-dependent manner, LDL reduced Cu2+ to Cu+. An LDL concentration as low as 10 micrograms of protein/ml (about 20 nM) reduced about 7 microM Cu2+ within 1 h of incubation. Complexation of the Cu+ formed under these conditions with BC significantly inhibited oxidative modification of LDL, as assessed by agarose gel electrophoresis. Preincubation of LDL with N-ethylmaleimide had no effect on the rate and extent of Cu2+ reduction nor LDL oxidation, indicating that free sulfhydryl groups associated with apolipoprotein B are not involved. Addition of either superoxide dismutase or catalase or increasing the alpha-tocopherol content of LDL from 11.8 +/- 3.0 to 24.4 +/- 2.8 nmol/mg of protein also had no significant effect on the kinetics of Cu2+ reduction by LDL. In contrast, incubation of LDL with Fe(3+)-citrate (10 microM) and the indicator bathophenanthroline (BP, 360 microM) resulted in no significant Fe2+ formation, even at LDL concentrations as high as 200 micrograms of protein/ml. However, incubation of LDL with Fe(3+)-citrate and an enzymatic source of superoxide led to rapid formation of Fe2+ and consequent oxidative modification of LDL. Addition of BP inhibited iron-mediated LDL oxidation under these conditions. Our results indicate that reduced metal ions are important mediators of LDL oxidation, and that LDL specifically reduces Cu2+, but not Fe3+. These data, therefore, help explain why copper, in addition to being chemically more reactive, is more potent than iron at mediating LDL oxidation.
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PMID:Reduction of copper, but not iron, by human low density lipoprotein (LDL). Implications for metal ion-dependent oxidative modification of LDL. 789 Jun 25

The aim of this study was to investigate the effects of chronic exposure to low density lipoprotein (LDL) and oxidised LDL (OXLDL) on phosphatidylinositol metabolism in bovine aortic endothelial cells. Basal levels of total inositol phosphates and inositol 1,4,5-trisphosphate were increased after both 18 and 66 h exposure to OXLDL 20 micrograms/ml. Levels also tended to be increased after exposure to LDL but this only reached significance for LDL 20 micrograms/ml after 18 h exposure. Absolute levels of inositol phosphates after stimulation with ATP were unaffected by incubation with LDL or OXLDL. However, when expressed as a percentage of basal levels, stimulated levels of inositol phosphates were reduced for ATP 10(-3) and 10(-4)M. Uptake of [3H]inositol into the phosphatidylinositol cycle was reduced after incubation with LDL and OXLDL for either 18 or 66 h. The effect of OXLDL was greater than that of LDL. The antioxidants EDTA and N-acetylcysteine attenuated the effects of LDL but not OXLDL. In addition, catalase but not mannitol or superoxide dismutase modified the effect of LDL on [3H]inositol uptake. These studies show that chronic exposure to OXLDL and to a lesser extent LDL can modify phosphatidylinositol metabolism in bovine aortic endothelial cells and that the effects of LDL may be attenuated by antioxidants and free radical scavengers. We hypothesise that the decreased uptake of [3H]inositol could be related to an alteration in membrane structure and integrity and may reflect alteration in transport of a number of ions and molecules.
Atherosclerosis 1994 May
PMID:Chronic exposure of bovine aortic endothelial cells to native and oxidized LDL modifies phosphatidylinositol metabolism. 794 59

Oxygen free radicals (OFR) are very reactive and unstable metabolites capable of altering important biomolecules including proteins, lipids and nucleic acids. OFR are regulated by enzymes such as superoxide dismutases (SOD), catalase, glutation peroxidase and by molecules such as vitamins E, A, C, and K, selenio, cystein and other compounds. Increased OFR levels due to an overproduction of these metabolites or to a failure in the control system, induce cellular and tissue injuries that could lead to diseases such as atherosclerosis, arthritis, fibrosis, lung and heart injuries, neurological disorders and cancer. In this article we consider the use of SOD as therapeutic agents both in human and experimental models. We also refer to the administration of SOD as a protective factor against secondary injuries during radiotherapy and to the determination of SOD as a tumor marker.
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PMID:[Free radicals of oxygen and superoxide dismutase. Biological and medical aspects]. 799 Jun 89


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