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Oxygen/Nitrogen Radicals: Cell Injury and Disease pp 19–25Cite as

Effects of antioxidants against atherosclerosis

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Part of the book series: Developments in Molecular and Cellular Biochemistry ((DMCB,volume 37))

Abstract

It is generally accepted that the oxidative modification of low density lipoprotein (LDL) plays a pivotal role in the progression of atherosclerosis. This suggests that the antioxidants which suppress the oxidative modification of LDL should be effective in preventing atherogenesis. This brief article reviews the role and potency of antioxidants against the oxidation of LDL. It is emphasized that the LDL can be oxidized by different oxidants by different mechanisms and the efficacy of antioxidants depends on the type of oxidants. (Mol Cell Biochem 234/235: 19–25, 2002)

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References

  1. Glass CK, Witztum JL: Atherosclerosis: The road ahead. Cell 104: 503–516, 2001

    Google Scholar 

  2. Steinberg D, Witztum JL: Lipoproteins, Oxidation, andAtherogenesis. In: K.R. Chien (ed). Molecular Basis of Cardiovascular Diseases. W.B. Saunders Co., Philadelphia, 1999, pp 458–475

    Google Scholar 

  3. Jha P, Flather M, Lonn E, Farkouh M, Yusuf S: The antioxidant vitamins and cardiovascular disease. A critical review ofepidemiologic and clinical trial data. Ann Intern Med 123: 860–872, 1995

    PubMed  CAS  Google Scholar 

  4. Esterbauer H, Gebicki J, Puhl H, Jurgens G: The role of lipid peroxidation and antioxidants in oxidative modification of LDL. Free Rad Biol Med 13: 341 390, 1992

    Google Scholar 

  5. Gotoh N, Noguchi N, Tsuchiya J, Morita K, Sakai H, Shimasaki H, Niki E: Inhibition of oxidation of low density lipoprotein by vitamin E and related compounds. Free Rad Res 24: 123–134, 1996

    Article  CAS  Google Scholar 

  6. Tsuchihashi H, Kigoshi M, Iwatsuki M, Niki E: Action of 13-carotene as an antioxidant against lipid peroxidation. Arch Biochem Biophys 323: 137–147, 1995

    Article  PubMed  CAS  Google Scholar 

  7. Niki E,Noguchi N,Tsuchihashi H,Gotoh N:Interaction among vitamin C, Vitamin E,andβ-carotene.Am J Clin Nutr 62(suppl):1322S–1326S, 1995

    Google Scholar 

  8. Niki E, Takahashi M, Komuro E: Antioxidant activity of vitamin E in liposomal membranes. Chem Lett 6: 1573–1576, 1986

    Article  Google Scholar 

  9. Barclay LRC: Model biomembranes: Quantitative studies of peroxidation, antioxidant action, partitioning, and oxidative stress. Can J Chem 71: 1–16, 1993

    Article  CAS  Google Scholar 

  10. Niki E: Free radicals in the 1900’s: Fromin vitrotoin vivo.Free Rad Res 33: 693–704, 2000

    Article  CAS  Google Scholar 

  11. Noguchi N, Iwaki Y, Takahashi M, Komuro E, Kato Y, Tamura K, Cynshi O, Kodama T, Niki E: 2,3-Dihydro-5-hydroxy-2,2-dipentyl-4,6-di-tert-butyl-benzofuran: Design and evaluation as a novel radical-scavenging antioxidant against lipid peroxidation. Arch Biochem Biophys 342: 236–243, 1997

    Article  PubMed  CAS  Google Scholar 

  12. Noguchi N, Okimoto Y, Tsuchiya J, Cynshi O, Kodama T, Niki E: Inhibition of oxidation of low-density lipoprotein by a novel antioxidant BO-653 prepared by theoretical design. Arch Biochem Biophys 347: 141–147,1997

    Article  PubMed  CAS  Google Scholar 

  13. Cynshi 0, Kawabe Y, Suzuki T, Takashima Y, Kaise H, Nakamura M, Noguchi N, Niki E, Kodama T: Antiatherogenic effects of the antioxidant BO-653 in three different animal models. Proc Natl Acad Sci USA 95: 10123–10128, 1998

    Article  PubMed  CAS  Google Scholar 

  14. Watanabe A, Noguchi N, Fujisawa A, Kodama T, Tamura K, Cynshi 0, Niki E: Stability and reactivity of aryloxyl radicals derived from a novel antioxidant BO-653 and related compounds. Effects of substituent and side chain in solution and membranes. J Am Chem Soc 122: 5438–5442, 2000

    Article  Google Scholar 

  15. Kamada N, Kodama T, Suzuki H: Macrophage scavenger receptor (SRAI/II) deficiency reduced diet-induced atherosclerosis in C57BL/6J mice. J Atheroscler Thromb 8: 1–6, 2001

    PubMed  CAS  Google Scholar 

  16. Niki E, Noguchi N: Antioxidant properties of probucol. In: L. Packer, E. Cadenas (eds). Handbook of Synthetic Antioxidants. Marcel Dekker, New York, 1997, pp 225–239

    Google Scholar 

  17. Zhang SH, Reddick RL, Avdievich E, Surles LK, Jones RG, Reynolds JB, Quarfordt SH, Maeda N: Paradoxical enhancement of atherosclerosis by probucol treatment in apolipoprotein E-deficient mice. J Clin Invest 99: 2858–2866, 1997

    Article  PubMed  CAS  Google Scholar 

  18. Benson AM, Batzinger RP, Ou SY, Bueding E, Cha YN, Talalay P: Elevation of hepatic gultathione 5-transferase activities and protection against mutagenic metabolities of benzo[a]pyrene by dietary antioxidants. Cancer Res 38: 4486–4495, 1978

    PubMed  CAS  Google Scholar 

  19. Cha YN, Martz F, Bueding E: Enhancement of liver microsome epoxide hydrolase activity in rodents by treatment with 2(3)-tert-butyl-4hydroxyanisole. Cancer Res 38: 4496–4498, 1978

    PubMed  CAS  Google Scholar 

  20. Keaney JF Jr, Simon DI, Freedman JE: Vitamin E and vascular homeostasis: Implications for atherosclerosis. FASEB J 13: 965–975, 1999

    PubMed  CAS  Google Scholar 

  21. Stewart-Lee AL, Forster LA, Nourooz-Zadeh J, Ferns GAA, Anggard EE: Vitamin E protects against impairment of endothelium-mediated relaxations in cholesterol-fed rabbits. Arterioscler Thromb 14: 494–499, 1994

    Article  PubMed  CAS  Google Scholar 

  22. Keaney JF Jr, Guo Y, Cunningham D, Shwaery GT, Xu A, Vita JA: Vascular incorporation of a-tocopherol prevents endothelial dysfunction due to oxidizied LDL by inhibiting protein kinase C stimulation. J Clin Invest 98: 386–394, 1996

    Article  PubMed  CAS  Google Scholar 

  23. Tasinato A, Boscoboinik D, Bartoli GM, Maroni P, Azzi A: d-Alphatocopherol inhibition of vascular smooth muscle cell proliferation occurs at physiological concentrations, correlates with protein kinaseC inhibition, and independent of its antioxidant properties. Proc Natl Acad Sci USA 92: 12190–12194, 1995

    Article  PubMed  Google Scholar 

  24. Farugi R, de la Motta C, DiCorleto P: Alpha-tocopherol inhibits agonist-induced monocytic cell adhesion to cultured human endothelial cells. J Clin Invest 94: 592–600, 1994

    Article  Google Scholar 

  25. Devaraj S, Li D, halal I: The effects of alpha-tocopherol supplementation on monocyte function: Decreased lipid oxidation interleukin 1 secretion, and monocyte adhesion to endothelium. J Clin Invest 98: 756–763,1996

    Article  PubMed  CAS  Google Scholar 

  26. Rao NK, Simon DI, Xu H, Keaney JF Jr: a-Tocopherol inhibits Mac-1 (CD1 1 b/CD18)-dependent monocyte adhesion. Circulation 96: 1489, 1997

    Google Scholar 

  27. Yoshida N, Yoshikawa T, Manabe H, Terasawa Y, Nondo M, Noguchi N, Niki E: Vitamin E protects against polymorphonuclear leukocyte-dependent adhesion to endothelial cells. J Leukocyte Biol 65: 757–763, 1999

    PubMed  CAS  Google Scholar 

  28. Rushmore TH, Morton MR, Pickett CB: The antioxidant responsive element. J Biol Chem 266: 11632–11639, 1991

    PubMed  CAS  Google Scholar 

  29. Frilling RS, Bensimon S, Daniel V: Xenobiotic-inducible expression of murine glutathione S-transferase Ya subunit gene is controlled by electrophile-responsive element. Proc Natl Acad Sci USA 87: 6258–6262, 1990

    Article  Google Scholar 

  30. Takabe W, Mataki C, Wada Y, Ishii M, Izumi A, Aburatani H, Hamakubo T, Niki E, Kodama T, Noguchi N: Gene expression induced by BO-653, probucol and BHQ in human endothelial cells. J Atheroscler Thromb 7: 223–230, 2000

    PubMed  CAS  Google Scholar 

  31. Takabe W, Kodama T, Hamakubo T, Tanaka K, Suzuki T, Aburatani H, Matsukawa N, Noguchi N: Anti-atherogenic antioxidants regulate the expression and function of proteasome a-type subunits in human endothelial cells. J Biol Chem 276:40497–40501, 2001

    Article  PubMed  CAS  Google Scholar 

  32. Azzi A, Stocker A: Vitamin E: Non-antioxidant roles. Prog Lipid Res 39: 231–255, 2000

    Article  PubMed  CAS  Google Scholar 

  33. Heinecke JW: Oxidants and antioxidants in the pathogenesis of atherosclerosis: implications for the oxidized low density lipoprotein hypothesis. Atherosclerosis 141: 1–15, 1998

    Article  PubMed  CAS  Google Scholar 

  34. Kuhn H, Chan L: The role of 15-lipoxygenase in atherogenesis: Pro-and antiatherogenic actions. Curr Opin Lipidol 8: 111–117, 1997

    Article  PubMed  CAS  Google Scholar 

  35. Cathcart MK, Folcik VA: Lipoxygenases and atherosclerosis: Protection vs. pathogenesis. Free Rad Biol Med 28: 1726–1734, 2000

    Article  PubMed  CAS  Google Scholar 

  36. Cyrus T, Witztum JL, Rader DJ, Tangirala R, Fazio S, Linton MF, Funk CD: Disruption of the 12/15-lipoxygenase gene diminishes atherosclerosis in apo E-deficient mice. J Clin Invest 103: 1597–1604, 1999

    Article  PubMed  CAS  Google Scholar 

  37. Harats D, Shaish A, George J, Mulkins M, Kurihara H, Levkovitz H, Sigal E: Overexpression of 15-lipoxygenase in vascular endothelium accelerates early atherosclerosis in LDL receptor-deficient mice. Arterioscler Thromb Vasc Biol 20: 2100–2105, 2000

    Article  PubMed  CAS  Google Scholar 

  38. Shen J, Herderick E, Cornhill JF, Zsigmond E, Kim HS, Kuhn H, Guevara NV, Chan L: Macrophage-mediated 15-lipoxygenase expression protects against atherosclerosis development. J Clin Invest 98: 2201–2208,1996

    Article  PubMed  CAS  Google Scholar 

  39. Heinecke JW: Pathways for oxidation of low density lipoprotein by myeloperoxidase: Tyrosyl radical, reactive aldehydes, hypochlorous acid and molecular chlorine. Biofactors 6: 145–155, 1997

    Article  PubMed  CAS  Google Scholar 

  40. Carr AC, McCall MR, Frei B: Oxidation of LDL myeloperoxidase and reactive nitrogen species: Reaction pathways and antioxidant protection. Arterioscler Thromb Vasc Biol 20: 1716–1723, 2000

    Article  Google Scholar 

  41. Hazen SL, Heinecke JW: 3-Chlorotyrosine, a specific marker of myeloperoxidase-catalyzed oxidation, is markedly elevated in low density lipoprotein isolated from human atherosclerotic intima. J Clin Invest 99: 2075–2081, 1997

    Article  PubMed  CAS  Google Scholar 

  42. Hazell LJ, Arnold L, Flowers D, Waeg G, Malle E, Stocker R: Presence of hypochlorite-modified proteins in human atherosclerotic lesions. J Clin Invest 97: 1535–1544, 1996

    Article  PubMed  CAS  Google Scholar 

  43. Noguchi N, Nakano K, Aratani Y, Koyama H, Kodama T, Niki E: Role of myeloperoxidase in the neutrophil-indueced oxidation of low density lipoprotein as studied by myeloperoxidase-knockout mouse. J Biochem 127: 971–976, 2000

    Article  PubMed  CAS  Google Scholar 

  44. Brennan ML, Anderson MM, Shih DM, Qu XD, Wang XP, Mehta AC, Lim LL, Shi WB, Hazen SL, Jacob JS, Crowley JR, Heinecke JW, Lusis AJ: Increased atherosclerosis in myeloperoxidase-deficient mice. J Clin Invest 107: 419–430, 2001

    Article  PubMed  CAS  Google Scholar 

  45. Davies MJ, Hawkins CL: Hypochlorite-induced oxidation of thiols: Formation of thiyl radicals and the role of sulfenyl chlorides as intermediates. Free Rad Res 33: 719–729, 2000

    Article  CAS  Google Scholar 

  46. Pullar JM, Vissers MCM, Winterbourn CC: Living with a killer: The effects of hypochlorous acid on mammalian cells. IUBMB Life 50: 259–266, 2000

    Article  PubMed  CAS  Google Scholar 

  47. Cheseny JA, Mahoney JR, Eaton JW: A spectrophotometric assay for chlorine-containing compounds. Anal Biochem 196: 262–266, 1991

    Article  Google Scholar 

  48. Can AC, Tijerina T, Frei B: Vitamin C protects against and reverses specific hypochlorous acid-and chloramine-dependent modifications of low-density lipoprotein. Biochem J 346: 491–499, 2000

    Article  Google Scholar 

  49. Upston JM, Witting PK, Brown AJ, Stocker R, Keaney JF Jr: Effect of vitamin E on aortic lipid oxidation and intimal proliferation after arterial injury in cholesterol-fed rabbits. Free Radic Biol Med 31: 12451253,2001

    Google Scholar 

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Author information

Authors and Affiliations

  1. Human Stress Signal Research Center, National Institute of Advanced Industrial Science and Technology (AIST), Ikeda, Japan

    Etsuo Niki

  2. Research Center for Advanced Science and Technology, University of Tokyo, Komaba, Tokyo, Japan

    Noriko Noguchi

Authors
  1. Etsuo Niki
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  2. Noriko Noguchi
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Editors and Affiliations

  1. Pathology and Physiology Research Branch, National Institute for Occupational Safety and Health, 1095 Willowdale Road Mall Stop B167, Morgantown, WV, 26505, USA

    Val Vallyathan , Xianglin Shi Ph.D.  & Vince Castranova ,  & 

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Niki, E., Noguchi, N. (2002). Effects of antioxidants against atherosclerosis. In: Vallyathan, V., Shi, X., Castranova, V. (eds) Oxygen/Nitrogen Radicals: Cell Injury and Disease. Developments in Molecular and Cellular Biochemistry, vol 37. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-1087-1_3

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  • DOI: https://doi.org/10.1007/978-1-4615-1087-1_3

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-5388-1

  • Online ISBN: 978-1-4615-1087-1

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