Antioxidant Vitamin Supplements and Cardiovascular Disease

Kris‐Etherton, Penny M.; Lichtenstein, Alice H.; Howard, Barbara V.; Steinberg, Daniel; Witztum, Joseph L.

doi:10.1161/01.cir.0000137822.39831.f1

Cited by 348 publications

(192 citation statements)

References 42 publications

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“…The better elucidated protein-tyrosine nitration mechanism supports a radical recombination of NO 2 • with protein-tyr • to produce 3-nitrotyrosine residues. Not unexpectedly, efficient Tyr nitration has been demonstrated so far with systems that directly or indirectly produce Tyr • in addition to NO 2…”

mentioning

confidence: 78%

“…D espite the substantial evidence indicating that oxidative mechanisms contribute to the pathogenesis of many human diseases, multiple large prospective intervention trials with classical antioxidants such as vitamin C, vitamin E and ␤-carotene failed to have a significant impact on disease risk and progression (1,2). Among the many reasons responsible for such inconclusive results, we may include incomplete knowledge of the chemical biology of redox processes and limited actions of classical antioxidants (2,3).…”

mentioning

confidence: 99%

“…Among the many reasons responsible for such inconclusive results, we may include incomplete knowledge of the chemical biology of redox processes and limited actions of classical antioxidants (2,3). The need to translate the basic information about cellular redox processes gained in the past 40 years into clinical applications justifies a better understanding of the properties of nonclassical antioxidants such as cyclic nitroxides (4).…”

mentioning

confidence: 99%

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Inhibition of myeloperoxidase-mediated protein nitration by tempol: Kinetics, mechanism, and implications

Vaz

Augusto

2008

Proc. Natl. Acad. Sci. U.S.A.

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Despite the therapeutic potential of tempol (4-hydroxy-2,2,6,6-tetra-methyl-1-piperidinyloxy) and related nitroxides as antioxidants, their effects on peroxidase-mediated protein tyrosine nitration remain unexplored. This posttranslational protein modification is a biomarker of nitric oxide-derived oxidants, and, relevantly, it parallels tissue injury in animal models of inflammation and is attenuated by tempol treatment. Here, we examine tempol effects on ribonuclease (RNase) nitration mediated by myeloperoxidase (MPO), a mammalian enzyme that plays a central role in various inflammatory processes. Some experiments were also performed with horseradish peroxidase (HRP). We show that tempol efficiently inhibits peroxidase-mediated RNase nitration. For instance, 10 M tempol was able to inhibit by 90% the yield of 290 M 3-nitrotyrosine produced from 370 M RNase. The effect of tempol was not completely catalytic because part of it was consumed by recombination with RNase-tyrosyl radicals. The second-order rate constant of the reaction of tempol with MPO compound I and II were determined by stopped-flow kinetics as 3.3 ؋ 10 6 and 2.6 ؋ 10 4 M ؊1 s ؊1 , respectively (pH 7.4, 25°C); the corresponding HRP constants were orders of magnitude smaller. Time-dependent hydrogen peroxide and nitrite consumption and oxygen production in the incubations were quantified experimentally and modeled by kinetic simulations. The results indicate that tempol inhibits peroxidase-mediated RNase nitration mainly because of its reaction with nitrogen dioxide to produce the oxammonium cation, which, in turn, recycles back to tempol by reacting with hydrogen peroxide and superoxide radical to produce oxygen and regenerate nitrite. The implications for nitroxide antioxidant mechanisms are discussed.antioxidant ͉ tyrosine ͉ tyrosine nitration ͉ nitroxides ͉ nitric oxide-derived oxidants

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confidence: 78%

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confidence: 99%

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confidence: 99%

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Inhibition of myeloperoxidase-mediated protein nitration by tempol: Kinetics, mechanism, and implications

Vaz

Augusto

2008

Proc. Natl. Acad. Sci. U.S.A.

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“…Clinical trial data not only indicate the lack of benefit with respect to glycemic control and progression of complications but also provide evidence of the potential harm of vitamin E, carotene, and other antioxidant supplements (1,72,73). In addition, available data do not support the use of antioxidant supplements for CVD risk reduction (74). Chromium, other minerals, and herbs in diabetes management.…”

Section: Optimal MIX Of Macronutrientsmentioning

confidence: 99%

Nutrition Recommendations and Interventions for Diabetes–2006

Bantle¹,

Wylie‐Rosett²,

Albright³

et al. 2006

Diabetes Care

194

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“…Moreover, accumulating in vitro and animal data continue to support a role for both vitamins, and especially for vitamin C, in countering multiple steps in the atherosclerotic process. In a commentary on this dichotomy, the Nutrition committee of the American Heart Association stated: "we recommend that antioxidant research continue in order to resolve whether the oxidative modification hypothesis is relevant to human atherosclerosis" (Kris-Etherton et al, 2004). This review deals with the potential role of vitamin C, or ascorbic acid, to prevent the early stages of atherosclerosis.…”

Section: Introduction: Atherosclerosis and Vitamin Cmentioning

confidence: 99%

Inflammation in the vascular bed: Importance of vitamin C

Aguirre

May

2008

Pharmacology & Therapeutics

111

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Despite decreases in atherosclerotic coronary vascular disease over the last several decades, atherosclerosis remains a major cause of mortality in developed nations. One possible contributor to this residual risk is oxidant stress, which is generated by the inflammatory response of atherosclerosis. Although there is a wealth of in vitro, cellular, and animal data supporting a protective role for antioxidant vitamins and nutrients in the atherosclerotic process, the best clinical trials have been negative. This may be due to the fact that antioxidant therapies are applied "too little and too late." This review considers the role of vitamin C, or ascorbic acid in preventing the earliest inflammatory changes in atherosclerosis. It focuses on the three major vascular cell types involved in atherosclerosis: endothelial cells, vascular smooth muscle cells, and macrophages. Ascorbate chemistry, recycling, and function are described for these cell types, with emphasis on whether and how the vitamin might affect the inflammatory process. For endothelial cells, ascorbate helps to prevent endothelial dysfunction, stimulates type IV collagen synthesis, and enhances cell proliferation. For vascular smooth muscle cells, ascorbate inhibits dedifferentiation, recruitment, and proliferation in areas of vascular damage. For macrophages, ascorbate decreases oxidant stress related to their activation, decreases uptake and degradation of oxidized LDL in some studies, and enhances several aspects of their function. Although further studies of ascorbate function in these cell types and in novel animal models are needed, available evidence generally supports a salutary role for this vitamin in ameliorating the earliest stages of atherosclerosis.

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Antioxidant Vitamin Supplements and Cardiovascular Disease

Cited by 348 publications

References 42 publications

Inhibition of myeloperoxidase-mediated protein nitration by tempol: Kinetics, mechanism, and implications

Inhibition of myeloperoxidase-mediated protein nitration by tempol: Kinetics, mechanism, and implications

Nutrition Recommendations and Interventions for Diabetes–2006

Inflammation in the vascular bed: Importance of vitamin C

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