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

To compare the chronic effect of several dialytic techniques (bicarbonate dialysis, BHD; acetate free biofiltration, AFB; hemodiafiltration, HDF; paired filtration dialysis, PFD) on atherosclerosis and antioxidant activity, three different indices were created. The first (atherosclerotic index = AI) is formed using the sum of three plasma substances: MDA, Hcy, and Cys (malondialdehyde, homocysteine, cysteine). The second (antioxidant activity index = AOAI) is the sum of five erythrocyte (E) parameters: E-GSH, GPx, CAT, SOD, GR (E-glutathione, E-glutathione peroxidase, E-catalase, E-superoxide dismutase, E-glutathione reductase). The third (defense index = DI) is derived from the previous two: (AOAI - AI). The indices were so expressed as AI in mmol/L, AOAI in U/g hemoglobin (Hb), and DI in arbitrary units. These indices were calculated in 20 controls and 51 chronic HD patients (26 female, 25 male) before, during, and after the first session of the week. HD patients were divided according to their dialytic technique: BHD, n = 35; AFB, n = 5 patients; HDF, n = 7 patients; or PFD = 4 patients. All patients had been treated with a given technique for at least 12 months, before entering the study. As expected, HD patients had AI values higher than controls, both before and after the session, with a mean value of 541 (before) and 331 (after), whereas controls had a mean value of 205. The AOAI was lower than controls, both before and after the session, the mean value being 1,122 (before) and 1,582 (after), that of controls being 2,424. In all cases, PFD gave the best "acute" results; at the end of a PFD session, near normal values of AI, AOAI, and DI (defensive index = AOAI - AI) were obtained.
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PMID:Do different dialytic techniques have different atherosclerotic and antioxidant activities? 1157 29

Oxidation of low-density lipoproteins (LDL) generates high concentrations of unsaturated aldehydes, such as 4-hydroxy trans-2-nonenal (HNE). These aldehydes are mitogenic to vascular smooth muscle cells and sustain a vascular inflammation. Nevertheless, the processes that mediate and regulate the vascular metabolism of these aldehydes have not been examined. In this communication, we report the identification of the major metabolic pathways and products of [(3)H]-HNE in rat aortic smooth muscle cells in culture. High-performance liquid chromatography separation of the radioactivity recovered from these cells revealed that a large (60-65%) proportion of the metabolism was linked to glutathione (GSH). Electrospray mass spectrometry showed that glutathionyl-1,4 dihydroxynonene (GS-DHN) was the major metabolite of HNE in these cells. The formation of GS-DHN appears to be due aldose reductase (AR)-catalyzed reduction of glutathionyl 4-hydroxynonanal (GS-HNE), since inhibitors of AR (tolrestat or sorbinil) prevented GS-DHN formation, and increased the fraction of the glutathione conjugate remaining as GS-HNE. Gas chromatography-chemical ionization mass spectroscopy of the metabolites identified a subsidiary route of HNE metabolism leading to the formation of 4-hydroxynonanoic acid (HNA). Oxidation to HNA accounted for 25-30% of HNE metabolism. The formation of HNA was inhibited by cyanamide, indicating that the acid is derived from an aldehyde dehydrogenase (ALDH)-catalyzed pathway. The overall rate of HNE metabolism was insensitive to inhibition of AR or ALDH, although inhibition of HNA formation by cyanamide led to a corresponding increase in the fraction of HNE metabolized by the GSH-linked pathway, indicating that ALDH-catalyzed oxidation competes with glutathione conjugation. These metabolic pathways may be the key regulators of the vascular effects of HNE and oxidized LDL.
Atherosclerosis 2001 Oct
PMID:Identification of biochemical pathways for the metabolism of oxidized low-density lipoprotein derived aldehyde-4-hydroxy trans-2-nonenal in vascular smooth muscle cells. 1158 12

The consumption of a cholesterol-enriched diet increases the degree of lipid peroxidation, which is one of the early processes of atherosclerosis. The aim of this trial was to determine the antioxidative effects of the citrus bioflavonoid, naringin, a potent cholesterol-lowering agent, compared to the cholesterol-lowering drug, lovastatin, in rabbits fed a high cholesterol diet. Male rabbits were served a high-cholesterol (0.5%, w/w) diet or high-cholesterol diet supplemented with either naringin (0.5% cholesterol, 0.05% naringin, w/w) or lovastatin (0.5% cholesterol, 0.03% lovastatin, w/w) for 8 weeks to determine the plasma and hepatic lipid peroxide, plasma vitamin A and E levels, and hepatic hydrogen peroxide levels, along with the hepatic antioxidant enzyme activities and gene expressions. Only the lovastatin group showed significantly lower plasma and hepatic lipid peroxide levels compared to the control group. The naringin supplementation significantly increased the activities of both hepatic SOD and catalase by 33% and 20%, respectively, whereas the lovastatin supplementation only increased the catalase activity by 23% compared to control group. There was no difference in the GSH-Px activities between the various groups. Content of H2O2 in hepatic mitochondria was significantly lower in groups supplemented with lovastatin and naringin than in control group. However, there was no difference in cytosolic H2O2 content in liver between groups. The concentration of plasma vitamin E was significantly increased by the naringin supplementation. When comparing the antioxidant enzyme gene expression, the mRNA expression of SOD, catalase and GSH-Px was significantly up-regulated in the naringin-supplemented group. Accordingly, these results would appear to indicate that naringin, a citrus bioflavonoid, plays an important role in regulating antioxidative capacities by increasing the SOD and catalase activities, up-regulating the gene expressions of SOD, catalase, and GSH-Px, and protecting the plasma vitamin E. In contrast, lovastatin exhibited an inhibitory effect on the plasma and hepatic lipid peroxidation and increased the hepatic catalase activity in high-cholesterol fed rabbits.
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PMID:Antioxidative activity of naringin and lovastatin in high cholesterol-fed rabbits. 1172 89

Extensive evidence suggests that reactive oxygen species are critically involved in the pathogenesis of cardiovascular diseases, such as atherosclerosis and myocardial ischemia-reperfusion injury. Consistent with this concept, administration of exogenous antioxidants has been shown to be protective against oxidative cardiovascular injury. However, whether induction of endogenous antioxidants by chemical inducers in vasculature also affords protection against oxidative vascular cell injury has not been extensively investigated. In this study, using rat aortic smooth muscle A10 cells as an in vitro system, we have studied the induction of cellular antioxidants by the unique chemoprotector, 3H-1,2-dithiole-3-thione [corrected] (D3T) and the protective effects of the D3T-induced cellular antioxidants against oxidative cell injury. Incubation of A10 cells with micromolar concentrations of D3T for 24 h resulted in a significant induction of a battery of cellular antioxidants in a concentration-dependent manner. These included reduced glutathione (GSH), GSH peroxidase, GSSG reductase, GSH S-transferase, superoxide dismutase, and catalase. To further examine the protective effects of the induced endogenous antioxidants against oxidative cell injury, A10 cells were pretreated with D3T and then exposed to either xanthine oxidase (XO)/xanthine, 4-hydroxynonenal, or cadmium. We observed that D3T pretreatment of A10 cells led to significant protection against the cytotoxicity induced by XO/xanthine, 4-hydroxynonenal or cadmium, as determined by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium reduction assay. Taken together, this study demonstrates for the first time that a number of endogenous antioxidants in vascular smooth muscle cells can be induced by exposure to D3T, and that this chemical induction of cellular antioxidants is accompanied by markedly increased resistance to oxidative vascular cell injury.
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PMID:Chemical induction of cellular antioxidants affords marked protection against oxidative injury in vascular smooth muscle cells. 1189 Jun 70

The possible involvement of oxidative damage in the progression of atherosclerosis has been suggested. There is some evidence that antioxidant therapy may be beneficial for the prevention of coronary heart disease. In this study, we investigated the relationship between coronary artery disease (CAD) and serum antioxidative status by measuring the total antioxidant status (TAS). Other relevant antioxidants, such as retinol, alpha, gamma-tocopherol, ascorbic acid, alpha, beta-carotenoids, erythrocyte glutathione peroxidase (GSH-Px) and oxidative products, were also determined in 31 male CAD patients with angiographically defined CAD and 66 male controls, aged 40-70 years, in a case-control study. The TAS levels, ratio and the concentrations of retinol, albumin, total protein and HDL cholesterol were significantly lower in the CAD patients than in the controls (p<0.01), and alpha-tocopherol and alpha/gamma-tocopherol were significantly higher in the CAD patients than in the controls. The TAS level correlated positively with gamma-GTP, GPT, GOT and uric acid (p<0.01). A multiple regression analysis in the CAD patients revealed that the TAS levels correlated most negatively with the number of diseased vessels. The concentrations of carotenoids and GSH-Px, as well as the alpha/gamma-tocopherol ratio were also significantly associated. Although conditional logistic regression analysis suggested low levels of HDL-cholesterol to be a significant coronary risk factor (OR=5.1, 95% CI=1.09-24.3), the TAS level showed no significant independent contribution to CAD. This study demonstrated an association of antioxidant parameters with the atherosclerosis progression, however, it did not confirm antioxidants as an independent risk factor for CAD event.
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PMID:Association of serum antioxidant capacity with coronary artery disease in middle-aged men. 1193 18

The purpose of this study was to investigate whether cholesterol plus methionine feeding may be a convenient model to produce atherosclerosis in rats, and also to examine the contribution of oxidative stress to this development. For this reason, lipid peroxide levels and antioxidant enzyme activities in the liver and aorta as well as histopathological findings were determined in male Wistar-albino rats fed a diet supplemented with cholesterol plus cholic acid and methionine for six months. This diet was found to increase lipid peroxide levels in the liver of rats. Hepatic glutathione peroxidase (GSH-Px) and catalase (CAT) activities increased, but superoxide dismutase (SOD) activity remained unchanged. In conclusion, cholesterol and methionine feeding in rats did not cause oxidative stress and atherosclerotic changes in the aorta, although hepatic prooxidant-antioxidant balance was affected by this diet.
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PMID:Cholesterol plus methionine feeding do not induce lipid peroxidation and atherosclerotic changes in the rat aorta. 1194 95

Hypochlorous acid (HOCl), generated by myeloperoxidase released from activated macrophages, is thought to contribute to vascular dysfunction and oxidation of low density lipoproteins (LDLs) in atherogenesis. We have previously shown that HOCl exposure can cause chlorination and oxidation of isolated DNA and that vitamin C protects human arterial smooth muscle cells against oxidized LDL-mediated damage. We report in the present study that vitamin C attenuates HOCl-induced DNA base and protein damage and depletion of intracellular glutathione (GSH) and ATP in human arterial smooth muscle cells. Cells were pretreated in the absence or presence of 100 micromol/L vitamin C (24 hours) and then exposed to HOCl (0 to 500 micromol/L, 0 to 60 minutes) in the absence of vitamin C. Intracellular GSH and ATP levels were depleted by HOCl treatment, and gas chromatography-mass spectroscopy revealed a concentration- and time-dependent increase in DNA base oxidation and protein damage (measured as 3-chlorotyrosine). Pretreatment of smooth muscle cells with vitamin C significantly reduced the extent of HOCl-induced DNA and protein damage and attenuated decreases in intracellular ATP and GSH. Our findings suggest that physiological levels of vitamin C provide an important antioxidant defense against HOCl-mediated injury in atherosclerosis.
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PMID:Vitamin C protects against hypochlorous Acid-induced glutathione depletion and DNA base and protein damage in human vascular smooth muscle cells. 1195 Jun 93

We used the apolipoprotein E deficient (apo e-/-) mice to analyze the role of macrophage reduced glutathione (GSH) content in cell-mediated oxidation of LDL and in atherosclerotic lesion development. Apo e-/- mice were supplemented with L-2-oxo-4-thiazolidin carboxylate (OTC, which supplies cysteine residues, 500 mg/kg/day), or with buthionine sulfoximine (BSO, a specific inhibitor of GSH synthesis, 400 mg/kg/day) for 6 weeks. Then mouse peritoneal macrophages (MPM) and the mice aortas were collected. MPM from apo e-/- mice contained decreased GSH levels (by 58%), and a four-fold increased lipid peroxides content compared to control macrophages from C57BL6 mice. These MPM demonstrated increased capability to release superoxide anions and to oxidize LDL in comparison to control MPM. OTC supplementation resulted in a 26% increase in macrophage GSH, paralleled by a 25% reduction in cellular lipid peroxides content. Decrement by 30% in superoxide anion release and LDL oxidation by MPM, and also in the atherosclerotic lesion size by 25%, was found in the OTC-treated mice, compared to placebo-treated apo e-/- mice. In contrast, in BSO-treated mice MPM a further depletion of cellular GSH by 22% was found, paralleled by a two-fold increase in lipid peroxides content, and a 41% increased superoxide anion release and cell-mediated LDL oxidation, compared to placebo-treated apo e-/- mice MPM. Most important, BSO supplementation to apo e-/- mice caused a 59% increase in the atherosclerotic lesion area. An additional way to increase cellular GSH content was the use of dietary antioxidants. Vitamin E (40 mg/kg/day) or the isoflavan glabridin (25 microg/kg/day) administration for 2 months to apo e-/- mice resulted in the accumulation of these antioxidants in their MPM, and increased MPM GSH content by 24 and 80%, respectively. MPM lipid peroxides content was reduced by 31 or 60% upon vitamin E or glabridin supplementation, paralleled by a 30 or 60% decrease in cell-mediated oxidation of LDL, respectively. Finally, a significant inverse correlation (R=0.83) was found between macrophage GSH content and cell-mediated oxidation of LDL. We conclude that enrichment in vivo of macrophages with GSH, significantly decreases cellular oxidative stress, leading to reduced capability of the macrophages to oxidize LDL, and hence GSH may attenuate the development of atherosclerosis.
Atherosclerosis 2002 Jul
PMID:Increased macrophage glutathione content reduces cell-mediated oxidation of LDL and atherosclerosis in apolipoprotein E-deficient mice. 1204 18

Advanced glycation end products (AGEs) play an important role in the development of angiopathy in diabetes mellitus and atherosclerosis. Here, we show that adducts of N(epsilon)-(carboxymethyl)lysine (CML), a major AGE, and bovine serum albumin (CML-BSA) stimulated gamma-glutamylcysteine synthetase (gamma-GCS), which is a key enzyme of glutathione (GSH) synthesis, in RAW264.7 mouse macrophage-like cells. CML-BSA stimulated the expression of gamma-GCS heavy subunit (h) time- and dose-dependently and concomitantly increased GSH levels. CML-BSA also stimulated DNA-binding activity of activator protein-1 (AP-1) within 3h, but the stimulatory effect decreased in 5h, and nuclear factor-kappaB (NF-kappaB) with a peak activity at 1h and the stimulatory effect diminished in 3h. Studies of luciferase activity of the gamma-GCSh promoter showed that deletion and mutagenesis of the AP-1-site abolished CML-BSA-induced up-regulation, while that of NF-kappaB-site did not affect CML-BSA-induced activity. CML-BSA also stimulated the activity of protein kinase C, Ras/Raf-1, and MEK/ERK1/2. Inhibition of ERK1/2 abolished CML-BSA-stimulated AP-1 DNA-binding activity and gamma-GCSh mRNA expression. Our results suggest that induction of gamma-GCS by CML adducts seems to increase the defense potential of cells against oxidative stress produced during glycation processes.
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PMID:Nepsilon-(Carboxymethyl)lysine induces gamma-glutamylcysteine synthetase in RAW264.7 cells. 1214 23

Hypertension and coronary artery disease are intimately connected. The migration of circulating monocytes into the subendothelial occurs through the expression of some adhesion molecules on endothelial cells. The nuclear factor (NF)-kappaB, a redox-sensitive element, plays a key role in adhesion molecule gene induction. In this study we have compared the effects of two different angiotensin converting enzyme (ACE) inhibitors, one possessing an active sulfhydryl group (zofenopril) and one lacking this group (enalapril) on the cellular redox state (monitored by measuring intracellular reactive oxygen species and thiol status), expression of adhesion molecules, and activation of NF-kappaB in human umbilical vein endothelial cells (HUVECs). Zofenoprilat, the active form of zofenopril, significantly and dose dependently reduced the intracellular reactive oxygen species (ROS) and superoxide formation induced by oxidized low-density lipoprotein (ox-LDL) (P <.001) and tumor necrosis factor-alpha (TNF-alpha) (P <.001). Enalaprilat, the active form of enalapril, was ineffective. Zofenoprilat but not enalaprilat also decreased the consumption of the intracellular GSH induced by ox-LDL (P <.01) and TNF-alpha (P <.01). Although zofenoprilat significantly and dose dependently reduced the expression of vascular cell adhesion molecule-1 (VCAM-1), intercellular cell adhesion molecule-1 (ICAM-1), and E-selectin induced by ox-LDL (P <.01) and TNF-alpha (P <.01) on HUVECs, enalaprilat did not. Ox-LDL and TNF-alpha increased the activation of NF-kappaB and the preincubation of HUVECs with zofenoprilat, but not with enalaprilat, dose dependently reduced its activation (P <.001). The conclusion is that the sulfhydryl (SH)-containing ACE inhibitors may be useful in inhibiting foam cell formation and thus slow the development of atherosclerosis.
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PMID:Zofenopril inhibits the expression of adhesion molecules on endothelial cells by reducing reactive oxygen species. 1237 76


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