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)

In humans, increased plasma homocysteine (Hcy) has been shown to be correlated with occlusive arterial diseases and atherosclerosis. Studies of isolated conductance vessels of experimental animals suggest that Hcy may interfere with local vasoregulatory mechanisms, yet the effect of hyperhomocysteinemia (HHcy) on the function of microvessels, such as skeletal muscle arterioles, has not been investigated. Male Wistar rats were divided into 2 groups: control rats (C; plasma Hcy, 7.1+/-0.3 micromol/L; n=25), and rats made HHcy by 1 g/kg body weight daily intake of methionine in the drinking water for 4 weeks (plasma Hcy, 23.6+/-2.9 micromol/L; P<0.01 versus C; n=25). First-order arterioles ( approximately 130 micrometer in diameter) were isolated from gracilis muscle, cannulated, and pressurized (80 mm Hg, no-flow conditions). Changes in diameter were observed by videomicroscopy. Arteriolar constrictions to norepinephrine (NE; 3x10(-7) mol/L) were significantly (P<0.01) greater in HHcy compared with C rats (C, 37.7+/-4.9%; HHcy, 59.5+/-5. 2%). Removal of the endothelium (-E) augmented NE-induced constrictions only in arterioles from C rats, whereas it had no effect on responses of arterioles from HHcy rats (C-E, 55.9+/-6.9%; HHcy-E, 56.5+/-7.0%). Dilations to cumulative doses of acetylcholine (ACh; 10(-8) mol/L) were significantly reduced in arterioles from HHcy rats (C, 64.0+/-5.2%; HHcy, 24.1+/-6.8%). Inhibition of nitric oxide (NO) synthesis with N(omega)-nitro-L-arginine (L-NNA; 10(-4) mol/L) significantly decreased ACh-induced dilations of C arterioles, whereas it did not affect HHcy arterioles. Similar alterations were found in arteriolar dilations to histamine, another known NO-dependent agonist. Endothelium-independent dilations to the NO donor sodium nitroprusside were not different in arterioles from C and HHcy rats, either in the presence or absence of L-NNA. Presence of superoxide dismutase and catalase (scavenger of reactive oxygen metabolites) did not affect HHcy-induced alterations in the ACh response. We conclude that hyperhomocysteinemia reduces rat skeletal muscle arteriolar dilations in response to ACh and histamine, and enhances constrictions to NE, alterations that are likely to be caused by the reduced mediation of these responses by NO. The reduced activity of NO in arterioles may contribute to the microvascular impairment described in HHcy.
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PMID:Dysfunction of nitric oxide mediation in isolated rat arterioles with methionine diet-induced hyperhomocysteinemia. 1044 68

Reactive oxygen metabolites such as hydrogen peroxide (H(2)O(2)) and oxidized fatty acids are proinflammatory and are involved in the pathophysiology of various diseases including atherosclerosis. The effects of these oxidants could be inhibited by the external addition of an antioxidant, suggesting the promotion or propagation of further oxidation. In this study, we describe the stable overexpression of human catalase in smooth muscle cells and the resistance of these cells to cytotoxicity induced not only by the addition of H(2)O(2) but also by the addition of 13-hydroperoxyoctadecadienoic acid (13-HPODE). The results pose an intriguing possibility of the generation of H(2)O(2) from a peroxidized fatty acid. Accordingly, incubation of cells with both 13-HPODE and 13-hydroxyoctadecadienoic acid resulted in the generation of intracellular H(2)O(2). To explain the observed results by which catalase could overcome the effects of 13-HPODE, we propose that oxidized fatty acids are degraded in the cellular peroxisomes, resulting in the generation of H(2)O(2). In other words, the cellular effects of peroxidized fatty acids could be attributed to the generation of H(2)O(2).
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PMID:Overexpression of human catalase gene decreases oxidized lipid-induced cytotoxicity in vascular smooth muscle cells. 1044 70

In recent years it has become apparent that the oxidation of lipids, or lipid peroxidation, is a crucial step in the pathogenesis of several disease states in adult and infant patients. Lipid peroxidation is a process generated naturally in small amounts in the body, mainly by the effect of several reactive oxygen species (hydroxyl radical, hydrogen peroxide etc.). It can also be generated by the action of several phagocytes. These reactive oxygen species readily attack the polyunsaturated fatty acids of the fatty acid membrane, initiating a self-propagating chain reaction. The destruction of membrane lipids and the end-products of such lipid peroxidation reactions are especially dangerous for the viability of cells, even tissues. Enzymatic (catalase, superoxide dismutasse) and nonenzymatic (vitamins A and E) natural antioxidant defence mechanisms exist; however, these mechanisms may be overcome, causing lipid peroxidation to take place. Since lipid peroxidation is a self-propagating chain-reaction, the initial oxidation of only a few lipid molecules can result in significant tissue damage. Despite extensive research in the field of lipid peroxidation it has not yet been precisely determined if it is the cause or an effect of several pathological conditions. Lipid peroxidation has been implicated in disease states such as atherosclerosis, IBD, ROP, BPD, asthma, Parkinson's disease, kidney damage, preeclampsia and others.
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PMID:Lipid peroxidation and tissue damage. 1045 7

Oxidative stress imposed by reactive oxygen species is now believed to contribute to hypertension, atherosclerosis and ageing of the vasculature all involving a loss of relaxation. The antioxidant enzymes glutathione peroxidase, superoxide dismutase and catalase play a crucial role in defending against the ravages of oxidative stress. Our purpose was to characterize age-related changes in glutathione peroxidase, superoxide dismutase and catalase in the rat aorta. Aortas were extracted from seven young (4 months), seven middle aged (18 months) and seven old (24 months) animals. Analysis of variance was used with Fisher-LSD post hoc to determine mean differences among glutathione peroxidase, superoxide dismutase and catalase. Aortic glutathione peroxidase activities rose steadily with age expressed in micromol mg protein-1 min-1 +/- SEM (young: 141 +/- 22; middle aged: 198 +/- 18; old: 229 +/- 26) reaching significance between young and old. Superoxide dismutase activities significantly decreased in middle aged when compared with young (young: 22 +/- 2 vs. middle aged: 15 +/- 2 U mg protein-1) before trending upward again in old age (19 +/- 2). Catalase activities dropped significantly between young and old when expressed in mU mg protein-1 (young: 230 +/- 30; middle aged: 173 +/- 18; old: 144 +/- 23). Ratios for the various enzymes indicate a shrinking contribution of catalase with ageing, with an enhanced role for glutathione peroxidase in the antioxidant defence. These data in aortas of ageing rats show a complex alteration of the antioxidant profile.
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PMID:Ageing alters aortic antioxidant enzyme activities in Fischer-344 rats. 1046 56

Nicotine, a major component of tobacco, is partly responsible for the development of atherosclerosis. It has been suggested that antioxidant nutrients are protective against degenerative diseases. So we have studied the antioxidant effect of oils isolated from onion and garlic on nicotine-induced lipid peroxidation in rat tissues. The lipid peroxidation products and scavenging enzymes were assessed in liver, lungs, heart and kidney. The rats were treated with 0.6 mg nicotine/kg bw and simultaneously given 100 mg garlic or onion oils/kg bw for 21 d. Thiobarbituric acid reactive substances, conjugated dienes and hydroperoxides concentrations were significantly increased in the tissues of nicotine-treated rats. Both the garlic oil and onion oil supplementation to nicotine-treated rats increased resistance to lipid peroxidation. The activities of catalase, superoxide dismutase and glutathione peroxidase decreased in nicotine-treated rats, but there was a trend to increased glutathione content. With garlic oil or onion oil supplementation, nicotine-treated rats had increased activities of antioxidant enzymes and increased concentrations of glutathione. These results indicate that oils of garlic and onion are effective antioxidants against the oxidative damage caused by nicotine.
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PMID:Antioxidant role of oils isolated from garlic (Allium sativum Linn) and onion (Allium cepa Linn) on nicotine-induced lipid peroxidation. 1050 36

Protein nitration and lipid peroxidation are implicated in the pathogenesis of atherosclerosis; however, neither the cellular mediators nor the reaction pathways for these events in vivo are established. In the present study, we examined the chemical pathways available to monocytes for generating reactive nitrogen species and explored their potential contribution to the protein nitration and lipid peroxidation of biological targets. Isolated human monocytes activated in media containing physiologically relevant levels of nitrite (NO(2)(-)), a major end product of nitric oxide ((*)NO) metabolism, nitrate apolipoprotein B-100 tyrosine residues and initiate LDL lipid peroxidation. LDL nitration (assessed by gas chromatography-mass spectrometry quantification of nitrotyrosine) and lipid peroxidation (assessed by high-performance liquid chromatography with online tandem mass spectrometric quantification of distinct products) required cell activation and NO(2)(-); occurred in the presence of metal chelators, superoxide dismutase (SOD), and scavengers of hypohalous acids; and was blocked by myeloperoxidase (MPO) inhibitors and catalase. Monocytes activated in the presence of the exogenous (*)NO generator PAPA NONOate (Z-[N-(3-aminopropyl)-N-(n-propyl)amino]diazen-1-ium-1,2- diolate) promoted LDL protein nitration and lipid peroxidation by a combination of pathways. At low rates of (*)NO flux, both protein nitration and lipid peroxidation were inhibited by catalase and peroxidase inhibitors but not SOD, suggesting a role for MPO. As rates of (*)NO flux increased, both nitrotyrosine formation and 9-hydroxy-10,12-octadecadienoate/9-hydroperoxy-10,12-octadecadieno ic acid production by monocytes became insensitive to the presence of catalase or peroxidase inhibitors, but they were increasingly inhibited by SOD and methionine, suggesting a role for peroxynitrite. Collectively, these results demonstrate that monocytes use distinct mechanisms for generating (*)NO-derived oxidants, and they identify MPO as a source of nitrating intermediates in monocytes.
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PMID:Formation of nitric oxide-derived oxidants by myeloperoxidase in monocytes: pathways for monocyte-mediated protein nitration and lipid peroxidation In vivo. 1055 42

Flavonoids are reported to exhibit a wide variety of biological effects, including antioxidant and free radical-scavenging activities. Reactive oxygen species have been implicated in a range of human pathological diseases such as atherosclerosis and certain cancers. The aims of this present study were 1) to investigate the effect of the flavonoids myricetin, quercetin, and rutin on cell viability, endogenous antioxidant enzyme activities, and DNA integrity in Caco-2 and Hep G2 cells and 2) to determine whether these flavonoids could protect against H2O2-induced DNA damage. Both cell lines were supplemented with various concentrations (0-200 microM) of myricetin, quercetin, and rutin for 24 hours or H2O2 (50 microM) for 30 minutes, and cell viability was assessed. Over the concentration range tested, neither the flavonoids nor H2O2 significantly affected cell viability. The effect of the flavonoids on the activities of the antioxidant enzymes catalase (EC 1.11.1.6) and superoxide dismutase (EC 1.15.1.1) and on DNA integrity was assessed. The flavonoids did not significantly affect catalase or superoxide dismutase activity and did not induce DNA damage in either cell line. Exposure to 50 microM H2O2 for 30 minutes at 37 degrees C resulted in significant DNA damage, and preincubation with the flavonoids before H2O2 exposure significantly (p < 0.05) protected Caco-2 and Hep G2 cells against H2O2-induced DNA damage.
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PMID:Protection by the flavonoids myricetin, quercetin, and rutin against hydrogen peroxide-induced DNA damage in Caco-2 and Hep G2 cells. 1057 83

Aldose reductase has been implicated in the etiology of diabetic complications, atherosclerosis, and ischemia-reperfusion injury. Aldose reductase inhibitors are known to have species-dependent differences in biotransformation enzyme induction. Whether aldose reductase inhibitors, which have antioxidant potential, alter the oxidative stress pathway is unknown. This study has determined whether four daily ip treatments of either low (10 mg/kg) or high (50 mg/kg) doses of AL-1576 or AL-4114 alter the activities of the antioxidant defense enzymes catalase, glutathione reductase, glutathione peroxidase, superoxide dismutase, and the concentrations of reduced and oxidized glutathione in livers of normal rats and rabbits. There was no change in the concentration of thiobarbituric acid reactive substances in either rat or rabbit livers, indicating that lipid peroxidation was not increased by any treatment. Hepatic catalase, superoxide dismutase, and glutathione peroxidase activities and concentrations of reduced and oxidized glutathione were not significantly altered in rat, though glutathione reductase activity was increased after high doses of both drugs. However, in rabbit liver, glutathione reductase activity decreased in a dose-dependent manner after AL-4114 treatment, while superoxide dismutase and glutathione peroxidase activities decreased only after the low dose of AL-4114. Although AL-4114 and AL-1576 did not directly generate increased lipid peroxidation within normal rat and rabbit livers, some of the enzymes responsible for oxidative defense were altered, particularly in rabbit livers.
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PMID:Effects of aldose reductase inhibitors on antioxidant defense in rat and rabbit liver. 1065 32

BACKGROUND: Investigations of the effects of high cholesterol diet in the presence and absence of garlic on the genesis of atherosclerosis, the blood lipid profile, aortic tissue lipid peroxidation product malondialdehyde, chemiluminescence, a marker for antioxidant reserve and activity of antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase were made in rabbits. METHODS AND RESULTS: Four groups of 10 rabbits each were studied: group 1 was given regular rabbit chow, group 2 was given rabbit chow diet supplemented with garlic powder (300 mg twice daily orally), group 3 was given 1% cholesterol diet, group 4 was given 1% cholesterol diet supplemented with garlic powder (300 mg twice daily orally). Blood concentration of triglyceride, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and very low-density lipoprotein cholesterol were measured before and after 4 and 10 weeks of experimental diets. The aorta was removed at the end of protocol (10 weeks) for assessment of atherosclerotic changes (gross and microscopic), malondialdehyde concentration, chemiluminescence, and activity of antioxidant enzymes. Total cholesterol, low density-lipoprotein cholesterol and ratio of low-density lipoprotein cholesterol/high-density lipoprotein cholesterol and ratio of low-density lipoprotein cholesterol/high-density lipoprotein cholesterol increaserd in group 3 and 4; the increase was smaller in group 4 than in in group 3 although not significant. Serum high-density lipoprotein cholesterol decreased to a similar extent in groups 3 and 4. Serum triglyceride and very low-density lipoprotein cholesterol remained unchanged in group 3 but increased in group 4. These values were significantly higher than those in group 1. Garlic in rabbits with control diet decreased the levels of triglyceride and very low density lipoprotein but did not affect the levels of total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol and the ratio of low-density lipoprotein cholesterol/high-density lipoprotein cholesterol. There was an increase in aortic tissue malondialdehyde, chemiluminescence, and activities of catalase and glutathione peroxidase in group 3 compared with those in group 1. Levels of aortic malondialdehyde, chemiluminescence, catalase, and glutathione peroxidase were lower in group 4 compared with group 3; however, values for malondialdehyde and chemiluminescence were lower and that of catalase and glutathione peroxidase were higher in group 4 compared with group 1. Superoxide dismutase activity was similar in all the four groups. Malondialdehyde, chemiluminescence, and activity of catalase of aortic tissue decreased while activity of glutathione peroxidase increased in group 2. Atherosclerotic changes were lower in group 4 compared with group 3. Histologic changes were practically similar in groups 3 and 4. CONCLUSIONS: Increased levels of malondialdehyde, chemiluminescence, and antioxidant enzymes associated with development of atherosclerosis suggests a role for oxygen free radicals in the pathogenesis of hypercholesterolemic atherosclerosis. The protection afforded by garlic was associated with decrease in aortic malondialdehyde and chemiluminescence inspite of no change in serum cholesterol. These findings suggest that oxygen free radicals are involved in the genesis and maintenance of hypercholesterolemic atherosclerosis and that use of garlic can be useful in preventing the development of hypercholesterolemic atherosclerosis.
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PMID:Prevention of Hypercholesterolemic Atherosclerosis by Garlic, an Antixoidant. 1068 72

The recruitment of monocytes via the endothelial expression of vascular cell adhesion molecule-1 (VCAM-1) is a key step in the formation of the initial lesion in atherosclerosis. Because angiotensin (Ang) II may be involved in this process, we investigated its role on the signaling cascade leading to VCAM-1 expression in endothelial cells. Ang II stimulates mRNA and protein expression of VCAM-1 in these cells via the AT(1) receptor. This effect was enhanced by N(G)-nitro-L-arginine methyl ester, a nitric oxide synthase inhibitor, and blocked by pyrrolidinedithiocarbamate, an antioxidant molecule. Ang II activated the redox-sensitive transcription factor nuclear factor-kappaB and stimulated the degradation of both inhibitor of kappaB (IkappaB)alpha and IkappaBbeta with different kinetics. The degradation of IkappaBs induced by Ang II was not modified by incubation with exogenous superoxide dismutase and catalase, suggesting that this effect was not mediated by the extracellular production of O(2)(-). In contrast, rotenone and antimycin, 2 inhibitors of the mitochondrial respiratory chain, inhibited the Ang II-induced IkappaB degradation, showing that generation of reactive oxygen species in the mitochondria is involved on Ang II action. BXT-51702, a glutathione peroxidase mimic, inhibited the effect of Ang II, and aminotriazole, an inhibitor of catalase, enhanced it, suggesting a role for H(2)O(2) in IkappaB degradation. This is confirmed by experiments showing that Ang II stimulates the intracellular production of H(2)O(2) in endothelial cells. These results demonstrate that Ang II induced an intracellular oxidative stress in endothelial cells, which stimulates IkappaB degradation and nuclear factor-kappaB activation. This activation enhances the expression of VCAM-1 and probably other genes involved in the early stages of atherosclerosis.
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PMID:Angiotensin II stimulates endothelial vascular cell adhesion molecule-1 via nuclear factor-kappaB activation induced by intracellular oxidative stress. 1071 86

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