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)

In 6 normal rabbits, the aortic arch, the descending thoracic and the abdominal aorta were tested for non proteic thiol compounds, selenium-dependent and selenium-independent glutatione peroxidase, glutatione reductase, glutatione transferase and thiobarbituric acid reactive substances. The aortic arch showed the greatest content of non proteic thiol compounds and thiobarbituric acid reactive substances, associated to the highest activities of glutathione-related enzymes. However, not significant differences were detectable between aortic arch and descending thoracic aorta, except for the glutathione transferase activity (0.395 +/- 0.031 vs 0.330 +/- 0.053 U/mg protein, p less than 0.05). Furthermore, both aortic arch and descending thoracic aorta showed significantly higher values of non proteic thiol compounds (46.05 +/- 10.15% and 33 +/- 13.5%, p less than 0.05), selenium-dependent glutathione peroxidase activity (70.35 +/- 26% and 54.3 +/- 9.5%, p less than 0.05), glutathione reductase activity (25.4 +/- 7% and 18.4 +/- 4.5%, p less than 0.05) and thiobarbituric acid reactive substances (65.8 +/- 18% and 47.2 +/- 17%, p less than 0.05) with respect to the abdominal aorta. The selenium-independent glutathione peroxidase activity was not detectable. In conclusion, a biochemical gradient in glutathione-related antioxidant defences and thiobarbituric acid reactive substances proceeding from the proximal to the distal segments seems to exist in the normal rabbit aorta. These results could contribute to explain the non homogeneous distribution of experimental atherosclerosis in the rabbit aorta.
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PMID:Regional distribution of glutathione-related antioxidant defences in the normal rabbit aorta. 204 54

In 24 rabbits fed a hyperlipidic diet (0.5% cholesterol, 5% lard and 5% peanut oil) for 10 (group A1), 30 group B1) and 60 days, (Group C1), compared to 24 control rabbits fed a standard diet for the same periods, antioxidant defence system (total superoxide dismutase, catalase, total thiol compounds selenium-dependent and selenium-independent glutathione peroxidase, glutathione reductase, glutathione transferase) and lipid peroxidation (thiobarbituric acid-reactive substances) in the aortic wall were tested. The percent of intima with grossly apparent atherosclerosis, is assessed by staining with the lipophilic dye Sudan IV, was negligible in group A1, but increased progressively in groups B1 (22.7-6.7%) and C1 (56.8-8.8%). Compared to the controls, a significant rise in superoxide dismutase activity was observed after 30 days of hyperlipidic diet, with a further marked increase at 60 days. Total thiol compounds and selenium-dependent glutathione peroxidase activity rose progressively from 10 to 30 and 60 days in cholesterol-fed rabbits. On the contrary, catalase, glutathione reductase and glutathione transferase activities significantly decreased in all experimental groups. Selenium-independent glutathione peroxidase activity was not detectable. Thiobarbituric acid-reactive substances increased about 3 times in hyperlipidemic rabbits. In conclusion, the changes in aortic antioxidant defence mechanisms and lipid peroxidation precede the massive vascular lipid infiltration in cholesterol-fed rabbits; some antioxidant mechanisms are stressed (superoxide, dismutase, glutathione peroxidase, total thiol compounds), whereas others are depressed (catalase, glutathione reductase, and glutathione transferase), thus potentially reducing or increasing vascular susceptibility to oxidative injury.
Atherosclerosis 1990 Mar
PMID:Aortic antioxidant defence mechanisms: time-related changes in cholesterol-fed rabbits. 232 23

In patients with diabetes mellitus, the processes of lipid peroxidation are activated and the system of antioxidants is disturbed (the content of reduced glutathione and red cell glutathione reductase is lowered and red cell glutathione peroxidase activity is heightened). At the same time the patients demonstrate high concentration of sterols bound by fibrinogen, a considerable lowering of cholesterol content in high density lipoproteins having an antiiatrogenic action. The alterations found underlie the development of atherosclerosis and coronary heart disease.
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PMID:[Interrelation of diabetes mellitus, atherosclerosis and ischemic heart disease]. 652 67

Oxidative damage due to free radical production is increased in uraemic patients and has been suggested as a possible factor contributing to the anaemia of chronic renal failure (CRF) and the pathogenesis of atherosclerosis. Oxidative stress was assessed in 40 patients with CRF maintained by either haemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD) and in 18 healthy controls. Lipid peroxidation (assessed as malondialdehyde, MDA), total glutathione (TG), antioxidant enzyme (glutathione reductase (GSHRx), glutathione peroxidase (GSHPx) and superoxide dismutase (SOD)) activity and antioxidant associated trace metal (selenium, copper, zinc) levels were studied. Erythrocyte membrane fluidity was examined using the fluorescent probe 1,6 diphenyl-1,3,5-hexatriene (DPH). The results indicate increased levels of oxidative stress and altered erythrocyte membrane fluidity in patients treated with CAPD compared with controls and patients treated with HD. Only minor changes were observed in patients treated with HD. Altered free radical activity, oxidative stress and altered erythrocyte membrane fluidity observed in patients with CRF may contribute to the increase in vascular disease in such patients and to the anaemia of CRF.
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PMID:Oxidative stress and erythrocyte membrane fluidity in patients undergoing regular dialysis. 755 72

We studied the relation between the glutathione (GSH) system and cell proliferation in a model of smooth muscle cells (SMC) derived from the thoracic aorta of 4-6-week-old (young) and 15-month-old (aged) rats. SMC from aged rats showed greater levels of total non-protein thiol compounds (T-SH), increased glutathione transferase (GST) and increased glutathione reductase (GSSG-Red) activities compared with cells from young rats. These changes were associated with an increased proliferation rate of SMC from aged rats. To evaluate the role of GSH on cell proliferation better, a specific inhibitor of gamma-glutamyl-cystein synthetase, DL-buthionine-SR-sulphoximine (BSO) was used. BSO showed a dose-dependent inhibition of cell growth, with an IC50 of 10(-4) M, after 48-72 h of incubation. Removal of BSO restored cell growth, further suggesting a link between GSH levels and vascular cell proliferation. The inhibitory effect of BSO was about two times greater on SMC from young than on SMC from aged rats. BSO showed 56% inhibition on the proliferation of SMC from young rats and 32% inhibition on SMC from aged rats (10(-4) M, 72 h of incubation). A parallel reduction of GSH levels of 38% and 19% for SMC from young and aged rats, respectively, was observed, suggesting that age-related factors may influence the involvement of GSH system in cell proliferation.
Atherosclerosis 1993 May
PMID:Differences in the glutathione system of cultured aortic smooth muscle cells from young and aged rats. 810 47

The oxidation of low density lipoprotein (LDL) may be important in atherosclerosis. LDL can be oxidized by cultured cells, including macrophages and endothelial cells. This cellular oxidation is dependent on transition metal ions in the medium. We now report that LDL oxidation by endothelial cells and macrophages is caused by cell-dependent appearance of thiol in the medium ("thiol production"). Thiol appeared in medium when cells were incubated under standard serum-free culture conditions. L-Cystine in the medium was required for thiol production and also for LDL oxidation. Cell-dependent appearance of thiol was inhibited by glutamate (which blocks cystine uptake) and by diethylmaleate (which reacts with thiols). Both compounds also blocked cellular LDL oxidation, even though neither compound had antioxidant activity. Finally, we designed an enzymatic system, based on glutathione reductase, that mimicked cellular thiol production. This enzymatic system caused LDL oxidation, and showed the same dependency for transition metal ions as did cellular LDL oxidation. We conclude that in media containing transition metal ions, cellular oxidation of LDL can be explained by the cell-dependent appearance of thiol in the medium. A very similar mechanism was proposed in 1987 by Heinecke et al. (J. Biol. Chem. 262: 10098-10103). Under other conditions, however, cellular oxidation of LDL may occur by other mechanisms.
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PMID:Cellular oxidation of low density lipoprotein is caused by thiol production in media containing transition metal ions. 810 88

Heart and red blood cell endogenous antioxidant status and plasma lipids were investigated in hypertensive, 14-week-old spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats fed a standard commercial rat chow. Specific heart and red blood cell antioxidant enzyme activities, as well as the susceptibility of tissues to H2O2-induced glutathione (GSH) depletion and lipid peroxidation, were measured. Systolic blood pressure in SHR was greater than in WKY rats at 13 weeks of age (197 +/- 12 vs. 132 +/- 14 mmHg (1 mmHg = 133.3 Pa); p < or = 0.05), confirming the presence of hypertension in SHR. Red blood cell catalase (CAT) and superoxide dismutase (SOD) activities were greater (p < or = 0.05) in SHR than WKY rats. Red blood cell CAT activity was positively correlated (r = +0.634; p = 0.026) with SOD, which in turn was correlated (r = +0.709; p = 0.049) with systolic blood pressure. Heart SOD activity was higher (p < or = 0.05) in SHR, while glutathione reductase (GSSG-Red) activity was lower (p < or = 0.05) than in WKY rats. This reduced ability to recycle GSH in the heart coincided with greater (p < or = 0.05) levels of H2O2-induced lipid oxidation products in SHR. Plasma total cholesterol and triacylglycerol levels were lower (p < or = 0.05) in SHR than WKY rats, with no visible signs of atherosclerosis in either SHR or WKY rats. In summary, hypertension in SHR was associated with alterations in antioxidant enzyme profiles of red blood cells and heart, with the latter showing an increased susceptibility to in vitro lipid oxidation. Although hypertension is a recognized factor in the development of human atherosclerosis, spontaneously hypertensive rats did not exhibit signs of aortic plaque, reflecting the resistance of this species to the development of atherosclerosis.
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PMID:Heart and red blood cell antioxidant status and plasma lipid levels in the spontaneously hypertensive and normotensive Wistar-Kyoto rat. 877 9

Nicotine, a major component of cigarette smoke, plays an important role in the development of cardiovascular disease and lung cancer in smokers. Lipid peroxidation is a process associated with the pathogenesis of atherosclerosis and the level of lipid peroxides is increased in smokers. In rats fed a high-fat diet, the tissue concentration of lipid peroxides was found to be increased. On nicotine administration along with a high-fat diet an additive effect was observed in lipid peroxidation and free radical scavengers. The activities of scavenging enzymes superoxide dismutase, catalase and glutathione reductase were found to be decreased, while the glutathione concentration and activity of glutathione peroxidase were enhanced.
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PMID:Effect of nicotine on antioxidant defence mechanisms in rats fed a high-fat diet. 884 84

Cigarette smoking has been established as a major risk factor for atherosclerosis and also for lung cancer. Nicotine is one of the major toxic components of cigarette smoke that is believed to be partly responsible for the deleterious effect of cigarette smoke. Alcohol intake is another major risk factor for the development of cardiovascular disease. Lipid peroxidation is a process associated with the pathogenesis of atherosclerosis. The concentration of lipid peroxides is found to be increased in alcohol-treated rats. On nicotine administration along with alcohol, an additive effect was observed in lipid peroxidation and the antioxidant defence mechanism. The activity of scavenging enzymes superoxide dismutase, catalase and glutathione reductase was found to be decreased, while the activity of glutathione peroxidase and the concentration of glutathione were increased.
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PMID:Additive effect of alcohol and nicotine on lipid peroxidation and antioxidant defence mechanism in rats. 885 16

The glutathione system plays a major role in the protection of cells against oxidative stress in humans. The aim of the present study was to find out the relationship between the glutathione system and plasma lipid peroxidation in six renal transplant recipients (who are under oxidative stress and thus at high risk for atherosclerosis), by using dietary selenium to activate the glutathione system. 2,2'-Azobis-2-amidinopropane hydrochloride (AAPH)-induced plasma lipid peroxidation was increased (by 60%) in all six patients in comparison to normal subjects. A similar pattern of increased plasma lipid peroxidation was found even in the basal state (in the absence of added AAPH). CuSO4-induced low-density lipoprotein (LDL) oxidation measured by peroxide formation was also significantly increased by 2.3-fold in the patients' LDL in comparison to normal LDL. Even in the absence of CuSO4, the LDL oxidation state was also increased in the patients' LDL in comparison to normal LDL. We thus analyzed the effect of dietary selenium (0.2 mg/day for a period of 3 months, followed by an additional 3 months on placebo) on plasma and on LDL lipid peroxidation. Selenium treatment resulted in a 50% reduction in AAPH-induced plasma lipid peroxidation. The susceptibility of the patients' plasma to lipid peroxidation returned toward baseline values 3 months after termination of the selenium treatment. Similar results, although less pronounced (only 15% reduction), were obtained for CuSO4-induced LDL oxidation. Analyses of the patients' red blood cell (RBC) glutathione system revealed low levels of reduced glutathione and decreased activities of RBC glutathione peroxidase and glutathione reductase by 23%, 18%, and 20%, respectively, in comparison to normal RBC. Selenium treatment resulted in a significant elevation of RBC glutathione peroxidase and glutathione reductase activities and in reduced glutathione content by 64%, 57%, and 11%, respectively; this effect was also paralleled by a 39% reduction in the RBC oxidized glutathione content. On termination of the selenium treatment, and after 3 months on placebo, all of these values of the glutathione system elements returned toward baseline levels. We thus conclude that dietary selenium, which activates the glutathione system, is a potent antioxidant against plasma and LDL lipid peroxidation in renal transplant recipients, and may thus be considered antiatherogenic.
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PMID:Dietary selenium increases cellular glutathione peroxidase activity and reduces the enhanced susceptibility to lipid peroxidation of plasma and low-density lipoprotein in kidney transplant recipients. 907 38


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