UMLS:C0004153 - FACTA Search

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

Arsenic is atherogenic, carcinogenic, and genotoxic. Because atherosclerotic plaque has been considered a benign smooth muscle cell tumor, we have studied the effects of arsenite on DNA integrity of human vascular smooth muscle cells. By using single-cell alkaline electrophoresis, apparent DNA strand breaks were detected in a 4-hour treatment with arsenite at a concentration above 1 micromol/L. DNA strand breaks of arsenite-treated cells were increased by Escherichia coli formamidopyrimidine-DNA glycosylase and decreased by diphenylene iodinium, superoxide dismutase, catalase, pyruvate, DMSO, or D-mannitol. Extract from arsenite-treated cells showed increased capacity for producing superoxide when NADH was included in the reaction mixture; however, addition of arsenite to extract from untreated cells did not increase superoxide production. The superoxide-producing ability of arsenite-treated cells was also suppressed by diphenylene iodinium, 4,5-dihydroxy-1, 2-benzenedisulfonic acid disodium salt (Tiron), or superoxide dismutase. Superoxide production and DNA strand breaks in arsenite-treated cells were also suppressed by transfecting antisense oligonucleotides of p22phox, an essential component of NADH oxidase. Treatment with arsenite also increased the mRNA level of p22phox. These results suggest that arsenite activates NADH oxidase to produce superoxide, which then causes oxidative DNA damage. The result that arsenite at low concentrations increases oxidant levels and causes oxidative DNA damage in vascular smooth muscle cells may be important in arsenic-induced atherosclerosis.
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PMID:NADH oxidase activation is involved in arsenite-induced oxidative DNA damage in human vascular smooth muscle cells. 1072 Apr 12

There is a large body of literature describing the causative role of oxidative stress mediated by increased levels of reactive oxygen species in the pathogenesis of cardiovascular disease such as atherosclerosis, hypertension, and restenosis after angioplasty. The positioning of a soft silicone collar around the rabbit carotid artery elicits intimal thickening. The findings from recent studies demonstrated that both intimal thickening and atherosclerosis lead to synthesis of inducible nitric oxide synthase, resulting in abundant amounts of nitric oxide. We investigated the effects of collaring and nicardipine treatment on the activities of antioxidant enzymes, superoxide dismutase and catalase, and total nitrite/nitrate levels, stable products of nitric oxide. Placing the collar increased the total nitrite/ nitrate levels and decreased superoxide dismutase activity in collared arteries. Treatment with nicardipine (20 mg/kg/day, s.c.) prevented enhanced nitric oxide degradation without affecting superoxide dismutase and catalase activities. Our results suggest that enhanced nitric oxide production and superoxide anion are generated in response to the collaring, resulting in oxidative stress within the segment in this model.
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PMID:Antioxidant enzyme activities and total nitrite/nitrate levels in the collar model. Effect of nicardipine. 1077 57

Glycated lipoproteins, which elevate the blood in diabetic patients, cause direct attenuation of endothelial function. Increased glycation of apolipoproteins may play a trigger role in the accelerated development of atherosclerosis in the patient with diabetes. Here we assessed whether glycated lipoproteins affect on the endothelial function with particular emphasis on the role of reactive oxygen species in vitro. Incubation of human aortic endothelial cells(HAEC) with glycated LDL had little influence on the expression of antioxidant enzymes such as nitric oxide synthase(NOS), Cu2+Zn(2+)-superoxide dismutase (Cu2+Zn(2+)-SOD), catalase, and p22 phox in the cells. In contrast, exposure of glycated HDL induced a marked decrease of Cu2+Zn(2+)-SOD, catalase, and endothelial NOS as well as a slight increase of p22 phox in HAEC in term of both protein and mRNA expression, suggesting that increased formation of reactive oxygen species such as O2- and OH radical participate in the deterioration for the function of vascular endothelial cells in diabetic patients.
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PMID:[Expression of reactive oxygen-species related enzymes in endothelial cells stimulated with glycated lipoproteins]. 1081 Aug 80

The objective of this study was to compare the effect of cholesterol feeding of rats and rabbits. The levels of lipid peroxidation products and oxysterols in the plasma of the two species plus the antioxidant enzyme activities in the liver and erythrocytes were measured to explain their different susceptibilities to atherosclerosis. Our study showed that rats are less susceptible than are rabbits to the atherogenic effect of a cholesterol-rich diet because of differences in lipid peroxidation products as well as antioxidant enzymes activities in their livers. In rabbits, cholesterol feeding produced severe hypercholesterolemia (43-fold increase) and increased plasma and liver lipid peroxidation. Total as well as the individual oxysterol contents of 7alpha-, 7beta-hydroxycholesterol, alpha-epoxy, beta-epoxycholesterol, cholestanetriol, 7-keto, and 27-hydroxycholesterol significantly increased in the plasma of hypercholesterolemic (HC) rabbits. Erythrocyte glutathione peroxidase (GSH-Px) activity significantly decreased whereas catalase activity significantly increased in HC rabbits. In rats cholesterol feeding increased the plasma cholesterol only twofold and had no effect on plasma or liver lipid peroxidation. Only 7alpha- and 7beta-hydroxycholesterol increased and no change was observed in any of the antioxidant enzymes activity in the erythrocytes. Although cholesterol feeding caused a 10-fold increase of liver cholesterol as ester in both rats and rabbits, the antioxidant enzyme GSH-Px and catalase activities in the liver significantly increased in rats but significantly decreased in rabbits. The increase of GSH-Px and catalase activities in the liver of cholesterol fed rats could have a protective role against oxidation, thus preventing the formation of lipid peroxidation and oxysterols.
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PMID:Cholesterol-rich diets have different effects on lipid peroxidation, cholesterol oxides, and antioxidant enzymes in rats and rabbits. 1087 4

Modulation of the biosynthesis of the vasoconstrictor peptide endothelin-1 by oxygen-derived free radicals generated by xanthine oxidase or hydrogen peroxide was studied in cultured endothelial cells. Endothelin-1 metabolism was investigated at the level of endothelin-1 promoter, preproendothelin-1 mRNA and intracellular big endothelin-1. Endothelin-1 mRNA, as characterized by Northern blotting, was increased both time- and dose-dependently by xanthine oxidase to up to 500% above baseline. Analysis of endothelin-1 promoter activity using a construct containing 1329 bp of the endothelin-1 promoter revealed that promoter activity was increased up to eight-fold by incubation with xanthine oxidase. Specificity was ascertained by co-incubation with superoxide dismutase and catalase leading to inhibition of the effect of xanthine oxidase. A significant contribution of nitric oxide was ruled out, since NOS III-mRNA transcription remained unchanged and l -NAME did not significantly alter endothelin-1 promoter activity. Synthesis of intracellular big endothelin-1 protein was increased dose-dependently by xanthine oxidase. Our results indicate that oxidative stress leads to increased endothelial synthesis of big endothelin-1, which is a previously unknown mechanism and may help to understand the detrimental association of increased oxidative stress and elevated endothelin-1 levels in pathophysiological conditions promoting atherosclerosis.
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PMID:Oxidative stress increases synthesis of big endothelin-1 by activation of the endothelin-1 promoter. 1090 Jan 69

The effects of exogenous oxidative stress due to passive smoking on cholesteryl ester (CE)-metabolizing enzymes and their regulatory kinases were examined by exposing rats to cigarette smoke (CS) for a 1-h period twice a day for 8, 12, or 20 wk. An oxidatively modified low density lipoprotein (Ox-LDL) with a high lipid peroxide was identified in three CS groups after all three exposure periods. The rat aortic acid and neutral CE hydrolases (ACEH and NCEH) were activated to similar extents by both cAMP-dependent protein kinase (PKA) and protein kinase C (PKC) in the presence of their respective cofactors. The aortic PKC activity in the three CS groups exhibited significant reductions of 72, 84, and 75% as compared with the respective controls, which coincided with the reductions in the ACEH activities (86, 71, and 80%, respectively), whereas the PKA activities increased to 121, 197, and 252% in the three CS groups, respectively. Reflecting the increase of the PKA activity, the NCEH activity exhibited increases of 112% at 8 wk and 140% until 12 wk of exposure and decreased by 50% of the control value at 20 wk of exposure, suggesting inactivation of NCEH itself. The activation of acyl-CoA:cholesterol O-acyltransferase activity was associated with an increase of free cholesterol in aorta. The vitamin E diet prevented the formation of Ox-LDL and the oxidative inactivation of most enzymes, especially PKC, until 12 wk, but was less effective by 20 wk. The oxidative inactivation of PKC, particularly its activated form that translocated to the membrane fraction, was confirmed in the in vitro exposure to active oxygen generators at an optimal concentration; this inactivation was prevented by catalase and superoxide dismutase. These results suggested that the formation of Ox-LDL and alterations in CE-metabolizing enzymes caused by passive smoking could contribute to a twofold increase in the aortic CE content, thereby contributing to one of the mechanisms for atherosclerosis associated with smoking.
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PMID:Effects of passive smoking on the regulation of rat aortic cholesteryl ester hydrolases by signal transduction. 1090 85

Various forms of oxidized low-density lipoproteins (Ox-LDL) are thought to play a major role in the development of atherosclerosis. The lipid components of Ox-LDL present a plethora of proatherogenic effects in in vitro cell culture systems, suggesting that oxidative stress could be an important risk factor for coronary artery disease. However, buried among these effects are those that could be interpreted as antiatherogenic. The present study demonstrates that various oxidants, including oxidized fatty acids and mildly oxidized forms of LDL (MO-LDL), are able to induce catalase (an antioxidant enzyme) expression in rabbit femoral arterial smooth muscle cells (RFASMC), RAW cells (macrophages), and human umbilical vein endothelial cells (HUVEC). In RFASMC, catalase protein, mRNA, and the enzyme activity are increased in response to oxidized linoleic acid (13-hydroperoxy-9,11-octadecadienoic acid [13-HPODE] and 13-hydroxy-9,11-octadecadienoic acid [13-HODE]), MO-LDL, or hydrogen peroxide (H(2)O(2)). Such an increase in catalase gene expression cannot totally be attributed to the cellular response to an intracellular generation of H(2)O(2) after the addition of 13-HPODE or 13-HODE because these agents induce a further increase of catalase as seen in catalase-transfected RFASMC. Taken together with the induction of heme oxygenase, NO synthase, manganese superoxide dismutase (Mn-SOD), and glutathione synthesis by oxidative stress, our results provide yet more evidence suggesting that a moderate oxidative stress can induce cellular antioxidant response in vascular cells, and thereby could be beneficial for preventing further oxidative stress.
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PMID:Lipid peroxides induce expression of catalase in cultured vascular cells. 1094 7

Lipid peroxides are suggested to be related to the occurrence of a variety of diseases including cancer and atherosclerosis. We examined whether lipid peroxides cause oxidative damage to DNA in intact cells. Linoleic acid hydroperoxide (LOOH) and ferric chloride were used at concentrations at which separate treatment had no effect on the formation of 8-oxo-2'-deoxyguanosine (8-oxodG) in DNA or the survival rate of cultured human diploid fibroblasts, TIG-7. The amount of 8-oxodG in the cellular DNA increased significantly when TIG-7 cells were treated concurrently with LOOH and ferric chloride. In a LOOH concentration-dependent manner 8-oxodG was formed. However, no significant induction of the activities of superoxide dismutases, catalase, or glutathione peroxidase was observed under these conditions. The formation of 8-oxodG by lipid hydroperoxides seems to be due to the generation of reactive species other than superoxide radicals and hydrogen peroxide. These results indicate that some species formed during the reaction of lipid hydroperoxides with ferric ion can cause oxidative damage to DNA.
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PMID:Formation of 8-oxo-2'-deoxyguanosine in the DNA of human diploid fibroblasts by treatment with linoleic acid hydroperoxide and ferric ion. 1102 16

Emerging evidence indicates that reactive oxygen species, especially superoxide and hydrogen peroxide, are important signaling molecules in cardiovascular cells. Their production is regulated by hormone-sensitive enzymes such as the vascular NAD(P)H oxidases, and their metabolism is coordinated by antioxidant enzymes such as superoxide dismutase, catalase, and glutathione peroxidase. Both of these reactive oxygen species serve as second messengers to activate multiple intracellular proteins and enzymes, including the epidermal growth factor receptor, c-Src, p38 mitogen-activated protein kinase, Ras, and Akt/protein kinase B. Activation of these signaling cascades and redox-sensitive transcription factors leads to induction of many genes with important functional roles in the physiology and pathophysiology of vascular cells. Thus, reactive oxygen species participate in vascular smooth muscle cell growth and migration; modulation of endothelial function, including endothelium-dependent relaxation and expression of a proinflammatory phenotype; and modification of the extracellular matrix. All of these events play important roles in vascular diseases such as hypertension and atherosclerosis, suggesting that the sources of reactive oxygen species and the signaling pathways that they modify may represent important therapeutic targets.
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PMID:Modulation of protein kinase activity and gene expression by reactive oxygen species and their role in vascular physiology and pathophysiology. 1103 Dec 1

Although philosophers and scientists have long been interested in the aging process, general interest in this fascinating and highly important topic was minimal before the 1960s. In recent decades, however, interest in aging has greatly accelerated, not only since the elderly form an ever-increasing percentage of the population, but because they utilize a significant proportion of the national expenditures. In addition, many people have come to the realization that one can now lead a very happy, active, and productive life well beyond the usual retirement age. Scientifically, aging is an extremely complex, multifactorial process, and numerous aging theories have been proposed; the most important of these are probably the genomic and free radical theories. Although it is abundantly clear that our genes influence aging and longevity, exactly how this takes place on a chemical level is only partially understood. For example, what kinds of genes are these, and what proteins do they control? Certainly they include, among others, those that regulate the processes of somatic maintenance and repair, such as the stress-response systems. The accelerated aging syndromes (i.e., Hutchinson-Gilford, Werner's, and Down's syndromes) are genetically controlled, and studies of them have decidedly increased our understanding of aging. In addition, C. elegans and D. melanogaster are important systems for studying aging. This is especially true for the former, in which the age-1 mutant has been shown to greatly increase the life span over the wild-type strain. This genetic mutation results in increased activities of the antioxidative enzymes, Cu-Zn superoxide dismutase and catalase. Thus, the genomic and free radical theories are closely linked. In addition, trisomy 21 (Down's syndrome) is characterized by a significantly shortened life span; it is also plagued by increased oxidative stress which results in various free radical-related disturbances. Exactly how this extra chromosome results in an increased production of reactive oxygen species is, however, only partially understood. There is considerable additional indirect evidence supporting the free radical theory of aging. Not only are several major age-associated diseases clearly affected by increased oxidative stress (atherosclerosis, cancer, etc.), but the fact that there are numerous natural protective mechanisms to prevent oxyradical-induced cellular damage speaks loudly that this theory has a key role in aging [the presence of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase, among others; various important intrinsic (uric acid, bilirubin, -SH proteins, glutathione, etc.) and extrinsic (vitamins C, E, carotenoids, flavonoids, etc.) antioxidants; and metal chelating proteins to prevent Fenton and Haber-Weiss chemistry]. In addition, a major part of the free radical theory involves the damaging role of reactive oxygen species and various toxins on mitochondria. These lead to numerous mitochondrial DNA mutations which result in a progressive reduction in energy output, significantly below that needed in body tissues. This can result in various signs of aging, such as loss of memory, hearing, vision, and stamina. Oxidative stress also inactivates critical enzymes and other proteins. In addition to these factors, caloric restriction is the only known method that increases the life span of rodents; studies currently underway suggest that this also applies to primates, and presumably to humans. Certainly, oxidative stress plays an important role here, although other, as yet unknown, factors are also presumably involved. Exactly how the other major theories (i.e., immune, neuroendocrine, somatic mutation, error catastrophe) control aging is more difficult to define. The immune and neuroendocrine systems clearly deteriorate with age. (ABSTRACT TRUNCATED)
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PMID:The biochemistry of aging. 1104 Sep 57

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