Anti-oxidants and pro-oxidants in coronary heart disease

Ra, Riemersma; Wood, David; Macintyre, C. C. A.; Elton, R. A.; Gey, K. F.; Oliver, M.F.

doi:10.1016/0140-6736(91)92496-o

Cited by 25 publications

(20 citation statements)

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“…Dietary supplementation with ␣ -tocopherol results in enhanced LDL ␣ -tocopherol content (14) and protection of LDL from copper-(14) and cell-mediated (13) oxidation in vitro. Plasma levels of ␣ -tocopherol are inversely correlated with the development of angina pectoris (15), and recent epidemiologic studies indicate that supplemental vitamin E consumption is inversely associated with the development of coronary artery disease in both men (16) and women (17).…”

Section: Introductionmentioning

confidence: 99%

Vascular incorporation of alpha-tocopherol prevents endothelial dysfunction due to oxidized LDL by inhibiting protein kinase C stimulation.

Keaney¹,

Guo²,

Cunningham³

et al. 1996

J. Clin. Invest.

199

114

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Excess vascular oxidative stress has been linked to impaired endothelium-dependent arterial relaxation in hypercholesterolemia. ␣ -Tocopherol (AT) preserves endothelial function in hypercholesterolemia although the mechanism(s) for this protective effect is (are) not known. We examined the tissue-specific effects of AT on oxidized LDL (ox-LDL)-mediated endothelial dysfunction in male New Zealand White rabbits. Animals consumed chow deficient in ( Ͻ 10 IU/kg) or supplemented with (1,000 IU/kg) AT for 28 d. Exposure of thoracic aortae from AT-deficient animals to ox-LDL (0-500 g/ml) for 4 h produced dose-dependent inhibition of acetylcholine-mediated relaxation ( P Ͻ 0.05) while vessels derived from animals consuming AT were resistant to ox-LDL-mediated endothelial dysfunction. Animals consuming AT demonstrated a 100-fold increase in vascular AT content and this was strongly correlated with vessel resistance to endothelial dysfunction from ox-LDL ( R ϭ 0.67; P ϭ 0.0014). These results were not explained by an effect of AT on ox-LDL-mediated cytotoxicity by LDH assay or scanning electron microscopy. Vascular incorporation of AT did produce resistance to endothelial dysfunction from protein kinase C stimulation, an event that has been implicated in the vascular response to ox-LDL. Human aortic endothelial cells loaded with AT also demonstrated resistance to protein kinase C stimulation by both phorbol ester and ox-LDL. Thus, these data indicate that enrichment of vascular tissue with AT protects the vascular endothelium from ox-LDL-mediated dysfunction, at least in part, through the inhibition of protein kinase C stimulation. These findings suggest one potential mechanism for the observed beneficial effect of AT in preventing the clinical expression of coronary artery disease that is distinct from the antioxidant protection of LDL. ( J. Clin. Invest. 1996. 98: 386-394)

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Section: Introductionmentioning

confidence: 99%

Vascular incorporation of alpha-tocopherol prevents endothelial dysfunction due to oxidized LDL by inhibiting protein kinase C stimulation.

Keaney¹,

Guo²,

Cunningham³

et al. 1996

J. Clin. Invest.

199

114

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“…An important link between free radical mediated cell damage and coronary heart disease is thought to be through oxidative damage of 532 D.I. Givens et al the PUFA in low density lipoprotein (LDL) cholesterol [31]. Vitamin E is one of the most powerful antioxidants and can prevent the damaging effects of free radicals, most important being the prevention of lipid oxidation in cell membranes.…”

Section: Introductionmentioning

confidence: 99%

“…There is increasing interest in the role of free radicals in the aetiology of a number of serious medical conditions, including CHD, thrombosis and some cancers [24,31]. An important link between free radical mediated cell damage and coronary heart disease is thought to be through oxidative damage of 532 D.I.…”

Section: Introductionmentioning

confidence: 99%

Enhancement of oleic acid and vitamin E concentrations of bovine milk using dietary supplements of whole rapeseed and vitamin E

2003

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-With the aim of reducing the degree of saturation and increasing the C18:1 cis fatty acid content of milk fat, the effects of feeding high levels of whole cracked rapeseed to dairy cows was investigated together with the effect of increasing dietary intake of vitamin E on the vitamin E content of milk. Using a 3 × 3 factorial design, 90 Holstein dairy cows were fed one of three levels of whole cracked rapeseed (0 (ZR), 134 (MR) and 270 g·kg -1 diet dry matter (DM) (HR)) in combination with one of three intakes of supplementary vitamin E (0 (ZE), 2 (ME) and 4 g·cow -1 ·d -1 (HE)). Supplementing with up to almost 2 kg·d -1 of rapeseed oil (diet HR) significantly (P < 0.001) increased C18:1cis in milk fat, from 181 (ZR) to over 400 g·kg -1 (HR) of total milk fatty acids. Concentrations of C18:0, C18:2 and C18:3 fatty acids were also increased (P < 0.001) but by a much lesser degree, and the saturated fatty acids C4:0 to C16:0 decreased substantially. Vitamin E supplementation increased (P < 0.01) milk vitamin E concentrations from 1.29 (ZE) to 1.68 mg·kg -1 whole milk (HE). Thus substantial changes in milk fat composition with potentially beneficial effects on human health were achieved and without any adverse effects on milk taste. However, these improvements must be offset against the substantial reductions (P < 0.001) observed in voluntary feed DM consumption (ZR, 20.6; HR, 15.2 kg DM·d -1 ), milk yield (ZR, 22.9; HR, 13.2 kg·d -1 ) and milk fat concentration (ZR, 42.1; HR, 33.4 g·kg -1 ) which would not be commercially sustainable unless a considerable premium was paid for this modified milk. It seems likely that the optimum dose of dietary rapeseed is lower than used in this study. Résumé -Augmentation de la concentration en acide oléique et en vitamine E du lait de bovin en incorporant dans la ration des graines de colza entières et de la vitamine E. Afin de réduire le degré de saturation des acides gras et d'augmenter la teneur en C18:1 cis du lait, les effets d'une alimentation avec des niveaux élevés de graines de colza concassées entières ont été étudiés chez des vaches laitières, en relation avec les effets de l'augmentation de l'ingestion de la vitamine E sur la teneur en vitamine E du lait. Au total, 90 vaches laitières de race Holstein ont été alimentées selon un schéma factoriel 3 × 3 avec trois niveaux de graines de colza concassées (0 (ZR), 134 (MR) et 270 g·kg -1 de matière sèche (HR)) et trois teneurs en vitamine E (0 (ZE), 2 (ME) et 4 g·vache -1 ·j -1 (HE)). La supplé-mentation avec près de 2 kg·j -1 d'huile de graines de colza (régime HR) a augmenté significativement (P < 0,001) la concentration du C18:1 cis du lait, de 181 (ZR) à plus de 400 g·kg -1 d'acides gras totaux du lait (HR). Les concentrations en C18:0, C18:2 et C18:3 ont été également augmentées (P < 0,001), mais dans des proportions moindres. Dans le même temps, la concentration des acides gras saturés C4:0 à C16:0 a diminué sensiblement. La supplémentation en vitamine E a augmenté les concentrations en vitamine E du lait ...

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“…Key Words: vitamin E Ⅲ cytokine Ⅲ interleukins Ⅲ protein kinase C Ⅲ leukotriene A lthough low levels of ␣-tocopherol (AT) are associated with increased risk for cardiovascular disease, increased intakes appear to be protective. [1][2][3][4][5][6] In addition to AT decreasing the oxidative susceptibility of LDL, 7-9 it could have effects on other crucial cells in atherogenesis, such as monocytes, that could prove beneficial. We previously showed that in vivo supplementation with AT significantly decreases monocyte superoxide anion release, lipid oxidation, interleukin-1␤ (IL-1␤) release, and adhesion to endothelial cells.…”

mentioning

confidence: 99%

α-Tocopherol Decreases Interleukin-1β Release From Activated Human Monocytes by Inhibition of 5-Lipoxygenase

Devaraj

Jialal

1999

ATVB

143

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Abstract-Cardiovascular disease is the leading cause of morbidity and mortality in westernized populations. Low levels of ␣-tocopherol (AT) are associated with increased incidence of atherosclerosis and increased intakes appear to be protective. Recently, we showed that supplementation with AT resulted in significant decreases in monocyte superoxide anion release, lipid oxidation, interleukin-1␤ (IL-1␤) release, and adhesion to endothelium. The reduction in superoxide and lipid oxidation by AT seemed to be mediated by inhibition of protein kinase C. The aim of this study was to investigate the mechanism(s) by which AT inhibits IL-1␤ release. Potential mechanisms examined included its effect as an antioxidant and its inhibitory effects on protein kinase C and the cyclooxygenase-lipoxygenase pathways. Although AT decreased superoxide release from activated monocytes, superoxide dismutase and catalase had no effect on IL-1␤ release. Also, a similar antioxidant, ␤-tocopherol, had no effect on IL-1␤ release. The protein kinase C inhibitor, bisindolylmaleimide, did not inhibit IL-1␤ release from activated monocytes, in spite of AT decreasing protein kinase C activity. Leukotriene B 4 , a major product of 5-lipoxygenase, has been shown to augment IL-1␤ release. In the presence of AT, a significant reduction in leukotriene B 4 and IL-1␤ levels was observed, which was reversed by the addition of leukotriene B 4 . Similar observations were seen with specific inhibitors of 5-lipoxygenase. The product of cyclooxygenase, prostaglandin E 2 , has been shown to inhibit IL-1␤ activity in some systems. However, AT had no significant effect on prostaglandin E 2 levels in activated monocytes. In the presence of indomethacin, a cyclooxygenase inhibitor, AT inhibited IL-1␤ activity. Also, AT had no effect on IL-1␤ mRNA levels or stability, suggesting a posttranscriptional effect. Thus, in activated human monocytes, AT exerts a novel biological effect of inhibiting the release of the proinflammatory cytokine, IL-1␤, via inhibition of the 5-lipoxygenase pathway. Key Words: vitamin E Ⅲ cytokine Ⅲ interleukins Ⅲ protein kinase C Ⅲ leukotriene A lthough low levels of ␣-tocopherol (AT) are associated with increased risk for cardiovascular disease, increased intakes appear to be protective. [1][2][3][4][5][6] In addition to AT decreasing the oxidative susceptibility of LDL, 7-9 it could have effects on other crucial cells in atherogenesis, such as monocytes, that could prove beneficial. We previously showed that in vivo supplementation with AT significantly decreases monocyte superoxide anion release, lipid oxidation, interleukin-1␤ (IL-1␤) release, and adhesion to endothelial cells. 10 In that study it appeared that the inhibition of superoxide anion release and lipid oxidation was mediated by inhibition of protein kinase C (PKC) by AT. However, we did not investigate the mechanism(s) by which AT inhibits IL-1␤ release and monocyte-endothelial cell adhesion. Recently, we showed that AT enrichment of monocytes decreased agonist-induced adhe...

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Anti-oxidants and pro-oxidants in coronary heart disease

Cited by 25 publications

References 0 publications

Vascular incorporation of alpha-tocopherol prevents endothelial dysfunction due to oxidized LDL by inhibiting protein kinase C stimulation.

Vascular incorporation of alpha-tocopherol prevents endothelial dysfunction due to oxidized LDL by inhibiting protein kinase C stimulation.

Enhancement of oleic acid and vitamin E concentrations of bovine milk using dietary supplements of whole rapeseed and vitamin E

α-Tocopherol Decreases Interleukin-1β Release From Activated Human Monocytes by Inhibition of 5-Lipoxygenase

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