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

Lipoxygenase is suggested to be involved in the early event of atherosclerosis by inducing plasma low-density lipoprotein (LDL) oxidation in the subendothelial space of the arterial wall. Since flavonoids such as quercetin are recognized as lipoxygenase inhibitors and they occur mainly in the glycoside form, we assessed the effect of quercetin and its glycosides (quercetin 3-O-beta-glucopyranoside, Q3G; quercetin 4'-O-beta-glucopyranoside, Q4'G; quercetin 7-O-beta-glucopyranoside, Q7G) on rabbit reticulocyte 15-lipoxygenase (15-LOX)-induced human LDL lipid peroxidation and compared it with the inhibition obtained by ascorbic acid and alpha-tocopherol, the main water-soluble and lipid-soluble antioxidants in blood plasma, respectively. Quercetin inhibited the formation of cholesteryl ester hydroperoxides (CE-OOH) and endogenous alpha-tocopherol consumption effectively throughout the incubation period of 6 h. Ascorbic acid exhibited an effective inhibition only in the initial stage and LDL preloaded with fivefold alpha-tocopherol did not affect the formation of CE-OOH compared with the native LDL. CE-OOH formation was inhibited by both quercetin and quercetin monoglucosides in a concentration-dependent manner. Quercetin, Q3G, and Q7G exhibited a higher inhibitory effect than Q4'G (IC50: 0.3-0.5 microM for quercetin, Q3G, and Q7G and 1.2 microM for Q4'G). While endogenous alpha-tocopherol was completely depleted after 2 h of LDL oxidation, quercetin, Q7G, and Q3G prevented the consumption of alpha-tocopherol. Quercetin and its monoglucosides were also exhausted during the LDL oxidation. These results indicate that quercetin glycosides as well as its aglycone are capable of inhibiting lipoxygenase-induced LDL oxidation more efficiently than ascorbic acid and alpha-tocopherol.
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PMID:Inhibition of mammalian 15-lipoxygenase-dependent lipid peroxidation in low-density lipoprotein by quercetin and quercetin monoglucosides. 944 20

The effective action of endothelium-derived nitric oxide (EDNO) is impaired in patients with atherosclerosis. This impairment has been attributed in part to increased vascular oxidative stress. EDNO action is improved by administration of ascorbic acid, a water-soluble antioxidant. Ascorbic acid is a potent free-radical scavenger in plasma, and also regulates intracellular redox state in part by sparing cellular glutathione. We specifically investigated the role of intracellular redox state in EDNO action by examining the effect of L-2-oxo-4-thiazolidine carboxylate (OTC) on EDNO-dependent, flow-mediated dilation in a randomized double-blind placebo-controlled study of patients with angiographically proven coronary artery disease. OTC augments intracellular glutathione by providing substrate cysteine for glutathione synthesis. Brachial artery flow-mediated dilation was examined with high-resolution ultrasound before and after oral administration of 4.5 g of OTC or placebo in 48 subjects with angiographically documented coronary artery disease. Placebo treatment produced no change in flow-mediated dilation (7.0+/-3.9% vs. 7.2+/-3.7%), whereas OTC treatment was associated with a significant improvement in flow-mediated dilation (6.6+/-4.4% vs. 11.0+/-6.3%; P = 0.005). OTC had no effect on arterial dilation to nitroglycerin, systemic blood pressure, heart rate, or reactive hyperemia. These data suggest that augmenting cellular glutathione levels improves EDNO action in human atherosclerosis. Cellular redox state may be an important regulator of EDNO action, and is a potential target for therapy in patients with coronary artery disease.
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PMID:L-2-Oxothiazolidine-4-carboxylic acid reverses endothelial dysfunction in patients with coronary artery disease. 950 83

The peroxidation step of lipid transormation is considered to be essential in the pathogenesis of atherosclerosis. Although data concerning the mechanisms by which lipid peroxidation occurs in vivo are scarce, several lines of evidence suggest that some endogenous and exogenous compounds with antioxidant activity could have some beneficial effects in the prevention of atherosclerosis. Ascorbic acid (vitamin C) and alpha-tocopherol (vitamin E) act as the most important hydrophilic and lipophilic antioxidants, respectively in vivo. Accordingly, animal and human studies suggest that these compounds may have some preventive effect against the development of clinical coronary heart disease. Many plant phenols and flavonoids may be important dietary antioxidants and it has been speculated that these compounds in red wine or in the Mediterranean diet could explain the 'French paradox'. Several studies show that antioxidants such as probucol and butylated hydroxytoluene can inhibit development of atherosclerotic lesions in Watanabe and cholesterol-fed rabbits. Some drugs such as beta-blockers, calcium antagonists, hypolipodemic drugs,...appear to have at least in vitro antioxidant effects but the clinical relevance of these properties remains unkonwn. Moreover, some interventions aimed to decrease the LDL-oxidative susceptibility have not been shown to attenuate atherogenesis when cholesterol levels remain markedly elevated.
Atherosclerosis 1998 Apr
PMID:LDL oxidation: therapeutic perspectives. 969 38

Several antioxidants inhibit atherosclerosis. This study investigated the hypothesis that combining vitamin E, a lipophilic antioxidant, with vitamin C, a hydrophilic antioxidant, and/or selenium, a cofactor of peroxidases that detoxify lipid peroxides, would inhibit atherosclerosis more effectively than vitamin E alone. We also considered whether regional variation in inhibition of atherosclerosis by antioxidants would be associated with regional variation in aortic lipophilic antioxidants. Rabbits were fed an atherogenic diet (control) or an atherogenic diet supplemented with vitamin E, vitamins E and C, vitamin E+selenium, vitamins E and C+selenium, or probucol (positive control). Supplements were as follows: vitamin E, 146 IU/d; vitamin C, 791 mg/d; selenium, 22 microg/d; or probucol, 406 mg/d. Vitamin C did not influence atherosclerosis. After 22 weeks of treatment, rank order of aortic atherosclerosis was control>vitamin E (with or without vitamin C)>vitamin E+selenium (with or without vitamin C)>probucol. Antioxidant treatment reduced aortic cholesterol concentrations 21% to 56%, 29% to 86%, and 19% to 75% for the aortic arch, descending thoracic aorta, and abdominal aorta, respectively (P<0.025 to P<0.0003 by ANOVA), with slightly greatly reductions for areas of atherosclerotic lesions. Some treatments reduced plasma cholesterol concentrations, but none altered the distribution of cholesterol among lipoproteins. Corrected for differences in plasma cholesterol concentrations, aortic cholesterol concentrations were reduced up to 72% (P<0.02) by the antioxidant treatments, with equal reductions by vitamin E+selenium and by probucol. Aortic alpha-tocopherol standardized by aortic cholesterol as a measure of aortic lipids was lower in the abdominal aorta than in the aortic arch of rabbits not given alpha-tocopherol and increased relatively more in the abdominal aorta than in the aortic arch with alpha-tocopherol supplementation. The results of this study suggest that vitamin E+ selenium inhibited atherosclerosis as effectively as an equally hypocholesterolemic dose of probucol by a mechanism(s) that is in part independent of effects on plasma and lipoprotein cholesterol concentrations. The tendency for greater efficacy of antioxidant treatments in the abdominal aorta than aortic arch may relate to the lower concentrations of alpha-tocopherol in the abdominal aorta of unsupplemented rabbits.
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PMID:Vitamin E combined with selenium inhibits atherosclerosis in hypercholesterolemic rabbits independently of effects on plasma cholesterol concentrations. 972 93

Melatonin has been suggested as a potent antioxidant that may protect against development of atherosclerosis and cancer; however, these effects are unproven and controversial. The antioxidant capacity of melatonin was tested in comparison with alpha-tocopherol, ascorbic acid, and the melatonin precursors tryptophan and serotonin, by measuring inhibition of metal ion-mediated and human macrophage-mediated oxidation of LDL. Melatonin had weak antioxidant activity that was detectable only at concentrations 10000- to 100000-fold higher than physiologic concentrations. These results were comparable with published data showing that the radical scavenging activity of melatonin requires markedly supraphysiologic concentrations. In contrast, alpha-tocopherol was 50- to 100-fold more potent and was efficacious at physiologic concentrations. Ascorbic acid and tryptophan also were active at physiologic concentrations and were significantly more potent than melatonin. In summary, extremely supraphysiologic concentrations of melatonin had only weak antioxidant activity, which was surpassed by alpha-tocopherol, ascorbic acid, and tryptophan.
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PMID:Inhibition of LDL oxidation by melatonin requires supraphysiologic concentrations. 973 79

Impaired endothelium-dependent vasodilation has been reported to play an important role in the pathogenesis of cardiovascular diseases such as coronary artery disease (CAD) and congestive heart failure (CHF). However, the precise mechanism of endothelial dysfunction has not been elucidated in these conditions. To evaluate the role of oxidative stress in endothelial dysfunction, the effect of antioxidant ascorbic acid on brachial flow-mediated, endothelium-dependent vasodilation during reactive hyperemia and nitroglycerin-induced endothelium-independent vasodilation was examined with high resolution ultrasound in 12 patients with CHF caused by idiopathic dilated cardiomyopathy without established coronary atherosclerosis and in 10 patients with CAD. Flow-mediated vasodilation in CHF (4.4+/-0.5%) and CAD (4.0 - 0.8%) was significantly (p <0.05) attenuated compared with that in 10 control subjects (9.6+/-0.9%). However, nitroglycerin-induced vasodilation was similar in 3 groups (13.7+/-1.3% in control, 13.9+/-1.1% in CHF, 12.7+/-1.4% in CAD). Ascorbic acid could significantly improve flow-mediated vasodilation only in patients with CAD (9.1+/-0.9%) but not with CHF (5.6+/-0.6%), and had no influence on nitroglycerin-induced vasodilation (13.6+/-1.1% in CHF, 14.0+/-1.3% in CAD). These results suggest that, in brachial circulation, augmented oxidative stress mainly leads to endothelial dysfunction in CAD but not in CHF caused by idiopathic dilated cardiomyopathy.
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PMID:Comparison of effects of ascorbic acid on endothelium-dependent vasodilation in patients with chronic congestive heart failure secondary to idiopathic dilated cardiomyopathy versus patients with effort angina pectoris secondary to coronary artery disease. 976 Oct 87

Ascorbic acid has been shown to enhance impaired endothelium-dependent vasodilation in patients with atherosclerosis by a mechanism that is thought to involve protection of nitric oxide (NO) from inactivation by free oxygen radicals. The present study in human endothelial cells from umbilical veins and coronary arteries investigates whether L-ascorbic acid additionally affects cellular NO synthesis. Endothelial cells were incubated for 24 h with 0.1-100 microM ascorbic acid and were subsequently stimulated for 15 min with ionomycin (2 microM) or thrombin (1 unit/ml) in the absence of extracellular ascorbate. Ascorbate pretreatment led to a 3-fold increase of the cellular production of NO measured as the formation of its co-product citrulline and as the accumulation of its effector molecule cGMP. The effect was saturated at 100 microM and followed a similar kinetics as seen for the uptake of ascorbate into the cells. The investigation of the precursor molecule L-gulonolactone and of different ascorbic acid derivatives suggests that the enediol structure of ascorbate is essential for its effect on NO synthesis. Ascorbic acid did not induce the expression of the NO synthase (NOS) protein nor enhance the uptake of the NOS substrate L-arginine into endothelial cells. The ascorbic acid effect was minimal when the citrulline formation was measured in cell lysates from ascorbate-pretreated cells in the presence of known cofactors for NOS activity. However, when the cofactor tetrahydrobiopterin was omitted from the assay, a similar potentiating effect of ascorbate pretreatment as seen in intact cells was demonstrated, suggesting that ascorbic acid may either enhance the availability of tetrahydrobiopterin or increase its affinity for the endothelial NOS. Our data suggest that intracellular ascorbic acid enhances NO synthesis in endothelial cells and that this may explain, in part, the beneficial vascular effects of ascorbic acid.
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PMID:L-Ascorbic acid potentiates nitric oxide synthesis in endothelial cells. 1007 31

Endogenous oxidative damage to proteins, lipids, and DNA is thought to be an important etiologic factor in aging and the development of chronic diseases such as cancer, atherosclerosis, and cataract formation. The pathology associated with these diseases is likely to occur only after the production of reactive oxygen species has exceeded the body's or cell's capacity to protect itself and effectively repair oxidative damage. Vitamin C, vitamin E, and beta-carotene, often referred to as "antioxidant vitamins," have been suggested to limit oxidative damage in humans, thereby lowering the risk of certain chronic diseases. However, epidemiological studies and clinical trials examining the efficacy of antioxidant vitamins, either individually or in combination, to affect disease outcome rarely address possible underlying mechanisms. Thus, in these studies it is often assumed that antioxidant vitamins act by lowering oxidative damage, but evidence in support of this contention is not provided. Therefore, in this review, we examine the scientific evidence that supplementation of humans with vitamin C, vitamin E, or beta-carotene lowers in vivo oxidative damage to lipids, proteins, or DNA based on the measurement of oxidative biomarkers, not disease outcome. With the only exception of supplemental vitamin E, and possibly vitamin C, being able to significantly lower lipid oxidative damage in both smokers and nonsmokers, the current evidence is insufficient to conclude that antioxidant vitamin supplementation materially reduces oxidative damage in humans.
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PMID:Can antioxidant vitamins materially reduce oxidative damage in humans? 1023 49

Vitamin C-deficiency is known to cause a disturbance of cholesterol metabolism. Suboptimal plasma ascorbic acid levels also cause increased blood histamine levels, which are exaggerated by sleep-lack and other forms of stress. Histaminemia causes separation of vascular endothelial cells. It is here suggested that the histaminemia of stress and ascorbate depletion combine to cause damage to the arterial endothelium and predispose to atherosclerosis, the principal cause of myocardial infarction.
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PMID:The key role of histamine in the development of atherosclerosis and coronary heart disease. 1034 62

There has been a growing interest during recent years in the role of free radicals and lipid-peroxidation at tissue-level for the causation of cancer and other age-related diseases like atherosclerosis, rheumatoid arthritis, cataract etc. Free radicals and increased lipid peroxidation play a significant role for causation of human diseases by oxidative damage and functional degeneration of the tissues. Vitamin C, a well-known dietary antioxidant, and other enzymatic antioxidants like glutathione can protect the lipids of lipoproteins and other biomembranes against peroxidative damage by intercepting oxidants before they can attack the tissues. But cigarette smoking was found to affect the antioxidant protective action of Vitamin C, glutathione etc. A group of adult male smokers in this study were found to have lowered Vitamin 'C' & glutathione levels, but increased lipid-peroxide levels in their blood. Thus the increased pathogenicity of the smoking may also be due to indirect biochemical effect of enhanced oxidative stress by increased lipid-peroxidation and lowered Vitamin C & other antioxidants at tissue-level.
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PMID:Influence of cigarette smoking on Vitamin C, glutathione and lipid peroxidation status. 1038 2


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