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

To elucidate the role of oxygen free radicals and lipid peroxidation in the pathogenesis of early hypertension and atherosclerosis, we studied the native distribution of three primary arterial antioxidant enzymes (AEs). Specific immunohistochemical localization of superoxide dismutase (Cu-Zn SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) was examined in the arterial wall of New Zealand White rabbits: six sham-operated normotensive/normolipidemics (NT/NL), seven coarctation-induced hypertensive/normolipidemics (HT/NL), eight normotensive diet-induced hyperlipidemics (NT/HL), and six hypertensive/hyperlipidemics (HT/HL). All three AEs were confined primarily to the endothelium in NT/NL rabbit aortas. However, in HT and HL rabbits a greater proportion of the arterial wall, including the endothelium, inner media, and middle media, displayed immunolocalization of three AEs. Multiple linear-regression analysis revealed that more than 70% of the total variability in the depth of immunolocalization of arterial AEs could be explained by changes in blood pressure and/or total cholesterol. Also, levels of plasma and arterial cholesterol oxides were significantly different (p less than 0.05) in HT and HL rabbits compared with controls, with twofold increases in NT/HLs, threefold increases in HT/NLs, and fourfold increases in HT/HLs. We conclude that intense free-radical activity in the arterial wall of HT and HL animals is one possibility and that this occurs despite the presence of abundant AEs.
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PMID:Immunolocalization of native antioxidant scavenger enzymes in early hypertensive and atherosclerotic arteries. Role of oxygen free radicals. 155 32

Copper-oxidized LDL has many of the characteristics of the modified LDL generated in the artery wall during the initial stages of atherosclerosis. It is not, however, a chemically defined species but shows significant variations in both its chemical composition and behaviour in biological systems depending upon the extent to which the peroxidation reaction has occurred (Fig. 1). Taking care to define the extent of LDL modification we have used this form of oxidized LDL to investigate the effects on the macrophage of this potentially toxic particle. This cell, in contrast to endothelial cells, appears to be particularly well adapted to detoxify lipid peroxidation products since it possesses glutathione peroxidases capable of metabolizing oxidized LDL and responds to oxidized LDL by increasing its GSH content. Acetylated LDL had little or no effect on GSH levels showing that lipid loading per se or recognition by the macrophage scavenger receptor is not sufficient to induce the synthesis of this antioxidant. We have confirmed the observation that oxidized LDL does not activate expression of the gene for TNF and raise the possibility that PGE2 produced by the cells and possibly during the oxidation of LDL may be the mediator suppressing the synthesis of this cytokine. Our results support the hypothesis that the lipid-laden macrophage does not contribute to an inflammatory response in the artery wall and imply a protective role for the macrophage in scavenging oxidized LDL.
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PMID:Oxidation of low-density lipoprotein and macrophage derived foam cells. 208 7

Selenium (Se) is an essential component of glutathione peroxidase (GSH-Px), an enzyme that protects cells by reducing intracellular peroxides. Impaired Se status and GSH-Px activity seem associated with increased risk of atherosclerotic vascular diseases. This study reports the effects of Se supplementation on GSH-Px activity, on prostacyclin (PGI2) production, on 12-hydroxy-eicosatetraenoic acid (12-HETE) levels, and on GSH-Px mRNA expression in cultured human umbilical vein endothelial cells (HUVEC). Se-enriched HUVEC showed significant increase of both GSH-Px activity and thrombin-stimulated production of PGI2 in the presence of stable concentrations of 12-HETE. On the other hand, an inverse correlation between Se concentrations in culture media and GSH-Px mRNA levels in Northern blot analysis was shown; this suggests that a major degree of regulation for GSH-Px expression by Se is most likely exerted at the posttranscriptional level. These observations may help to explain the increased incidence of atherosclerosis described in Se-deficient individuals.
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PMID:Selenium enhances glutathione peroxidase activity and prostacyclin release in cultured human endothelial cells. Concurrent effects on mRNA levels. 788 76

Oxidative modification of human low-density lipoprotein (LDL) is thought to play an important role in the development of atherosclerosis. LDL oxidizability is believed to be strongly influenced by factors such as (a) content of preexisting lipid hydroperoxides (LOOHs) and (b) content of endogenous antioxidants such as alpha-tocopherol and beta-carotene. The purpose of this study was to examine the prooxidant role of preexisting LDL-LOOHs, using a recently developed method for ultrasensitive and selective LOOH analysis: high-performance liquid chromatography with mercury drop electrochemical detection (HPLC-EC). Exceedingly low detection limits for LDL-LOOHs have been achieved by HPLC-EC, e.g., approximately 100 fmol for cholesteryl ester hydroperoxide (CEOOH). This sensitivity has allowed us to monitor LDL-LOOHs at levels that are undetectable by most other methods. Fresh LDL prepared with the utmost care to prevent autoxidation was found to contain small, yet significant amounts of CEOOH, 6-12 pmol/mg protein. Our data suggest that these peroxides could not have arisen during LDL isolation or sample work-up for HPLC-EC. Incubation with GSH and phospholipid hydroperoxide glutathione peroxidase resulted in nearly complete reduction of the CEOOH. This LDL was found to be much more resistant to Cu(2+)-induced peroxidation than starting material, exhibiting a lag period that was at least six times greater. We have also determined that LDL becomes progressively more susceptible to Cu(2+)-induced lipid peroxidation (as evidenced by a shortened lag) when it is preloaded with increasing amounts of photochemically generated LOOHs. Taken together, these results provide strong support for the idea that preexisting LOOHs in LDL are important determinants of its overall oxidizability.
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PMID:Involvement of preexisting lipid hydroperoxides in Cu(2+)-stimulated oxidation of low-density lipoprotein. 798 64

The determination of lipid hydroperoxides in plasma and lipoproteins recently reached a clinical relevance in disorders such as atherosclerosis, where oxidative reactions have been suggested to play a fundamental pathogenetic role. The peroxide content of lipoproteins is usually measured after ultracentrifugation and extraction. During this procedure, some peroxides might decompose causing a too low recovery. To screen this possibility, the disappearance, in the presence of human plasma, of hydroperoxides of linoleic acid and Cu-oxidized low density lipoprotein (LDL) have been investigated, using both a iodometric titration and an enzymatic assay. While only in the presence of GSH plasma decomposes linoleic acid hydroperoxides quite rapidly, peroxides in Cu-oxidized LDL were stable both in presence as well as in absence of GSH. This indicated that lipid hydroperoxides are stable in plasma and that peroxides of Cu-oxidized LDL are not substrate for the glutathione-dependent peroxidase activity in plasma. The relevant decrease of the iodometric titre of LDL peroxides observed in the presence of elevated amounts of plasma was shown to be artifactual, since some compounds extracted from plasma do react with iodine generated by peroxides. Whole plasma itself, indeed, has been shown to reduce back to I- appreciable amount of free iodine.
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PMID:Effect of plasma on the degradation of hydroperoxides of unesterified linoleic acid and copper-peroxidized LDL. 800 31

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

61 spa patients, predominantly with heart and vascular diseases, were divided into 2 therapeutic groups. In addition to the usual balneotherapeutic program, one group (J) received a course of "iodine brine concentrate" for drinking (2 x 100 ml, daily iodine uptake approximately 9 mg), and the control group (CI) received isotonic NaCl in the same way. The patients were mostly on a reduced-fat and -calorie diet. The following parameters were determined at the beginning and at the end of the 26-day treatment period: total cholesterol, HDL-cholesterol, triglycerides, lipoprotein (a) (in serum); selenium (Se), malondialdehyde (MDA), and activities of Se-dependent, Se-independent, and total glutathione peroxidase (GSH-PX) (in plasma). In the J group, a significant increase was found in Se-independent (+17%) and total GSH-PX (+5%) and a significant decrease in total cholesterol (-6.9%) and MDA (-13.2%). At the end of the cure, Se levels were higher in the J group than in the C1 group. The only significant change in the C1 group was a decrease in HDL-cholesterol. Positive correlations were found between selenium and Se-dependent GSH-PX (r = 0.253) and between total GSH-PX and Se-dependent GSH-PX (r = 0.665). A negative correlation was obtained between Se-dependent and Se-independent GSH-PX (r = -0.331). The results are discussed with regard to the importance of antioxidant defense mechanisms in several degenerative diseases (atherosclerosis, diabetes, cataract etc.), and also respecting interactions between iodine and selenium metabolism, as well as normalization effects conditioned by the balneotherapy itself.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Changes in selenium status, antioxidant enzyme activity and lipid peroxide level after drinking cures in Bad Hall health resort]. 814 96

In 41 patients with coronary heart disease (CHD) the concentrations of total blood platelet malonyldialdehyde (MDA: 2.11 +/- 0.25 nmol/10(9) platelets) and MDA corresponding to thromboxane A2 (TXA2 0.84 +/- 0.13 nmol/10(9) platelets) were increased in comparison with values in blood platelets of healthy subjects (1.19 +/- 0.09 and 0.71 +/- 0.05 nmol/10(9) platelets), respectively. The increased aggregability with ADP and thrombin of patient platelets was also observed. In relation to the blood platelets of healthy subjects, the antioxidant enzymes activities of patient blood platelets were significantly (P < 0.001) decreased. Platelet glutathione peroxidase (GSH-Px) activity of the patients (11.3 +/- 0.85 U/g protein) was significantly lower than controls (18.3 +/- 1.12 U/g protein). In patients with CHD the activities of the other antioxidative platelet enzymes: catalase (Cat, 7.37 +/- 1.38 U/g protein) and superoxide dismutase (SOD, 1529.4 +/- 167 U/g protein) were also significantly decreased in comparison with values for healthy subjects (Cat: 9.06 +/- 1.30 U/g protein and SOD: 1987 +/- 230 U/g protein, respectively). It is suggested that antioxidative defense in blood platelets may affect the haemostatic processes and lipid peroxidation in patients with CHD.
Atherosclerosis 1993 May
PMID:Changes in antioxidant enzymes activities, aggregability and malonyldialdehyde concentration in blood platelets from patients with coronary heart disease. 835 54

We investigated the effects of high cholesterol diet in the absence and presence of vitamin E on the activity of antioxidant enzymes [superoxide dismutase (SOD), catalase, glutathione peroxidase (GSH-Px)] in rabbits. The animals were divided into 4 groups each comprising of 10 rabbits. Group I, regular rabbit chow diet; Group II, regular rabbit chow diet with added vitamin E; Group III, high cholesterol diet; and Group IV, high cholesterol diet+vitamin E. Antioxidant enzymes of blood were measured in each group before and after 1, 2, 3, and 4 months on the experimental diets. The aorta was removed at the end of the protocol for measurement of antioxidant enzymes. There was a decrease in activity of SOD and GSH-Px and an increase in activity of catalase in blood of Group III. Vitamin E produced a decrease in blood SOD, catalase and GSH-Px activity in Group II and prevented the decrease in SOD and GSH-Px activity in Group IV but did not affect the changes in the catalase activity. SOD, catalase and GSH-Px activity of aortae from Group III increased significantly, while catalase activity increased and GSH-Px activity decreased in those from Group II. Vitamin E prevented the cholesterol-induced rise in catalase and GSH-Px activity in aorta but did not prevent the rise in SOD activity. These results suggest that the activity of antioxidant enzymes in blood is affected differently from that in aortic tissue. There appears to be a mutually supportive interaction among the antioxidant enzymes which provide defense against oxidant injury. The protective effects of vitamin E against hypercholesterolemic atherosclerosis may not be due to changes in the antioxidant enzymes but may be mainly mediated through its chain-breaking antioxidant activity.
Atherosclerosis 1993 Jul
PMID:Antioxidant enzymes in hypercholesterolemia and effects of vitamin E in rabbits. 837 58

Effects of high cholesterol diet (0.5% and 1%) on the activity of antioxidant enzymes [superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px)] in the aortic tissue of rabbits were investigated in the absence or presence of probucol (0.5 gm/kg daily, orally). Five groups of ten rabbits each were studied. Group I, regular rabbit chow diet; Group II, chow + 0.5% cholesterol; Group III, chow + 0.5% cholesterol+probucol; Group IV, chow + 1% cholesterol and Group V, chow + 1% cholesterol+probucol. The aorta was removed at the end of 4 months for measurement of the antioxidant enzymes. An increase in activity of aortic antioxidant enzymes was noted in cholesterol-fed rabbits (Groups II and IV), being similar for SOD and catalase but higher for GSH-Px in Group IV as compared to Group II. Probucol was ineffective in altering this cholesterol-induced increase in enzyme activity except in Group III where it increased the activity of GSH-Px. These results suggest that aortic antioxidant enzymes are affected in hypercholesterolemia and that probucol is ineffective in altering the aortic antioxidant enzyme activity except GSH-Px activity which increased in 0.5% cholesterol-fed rabbits. The protective effects of probucol against hypercholesterolemic atherosclerosis may be partly due to an increase in the GSH-Px activity at low levels of hypercholesterolemia. At higher levels of hypercholesterolemia, the protective effects of probucol could be due to its antioxidant activity.
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PMID:Effects of probucol on hypercholesterolemia-induced changes in antioxidant enzymes. 856 23


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