Skip to main content
SpringerLink
Log in

Inhibition of Lipoprotein Lipid Oxidation

  • Chapter
Book cover Atherosclerosis: Diet and Drugs

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 170))

Abstract

According to the oxidative modification hypothesis, antioxidants that inhibit the oxidation of low-density lipoprotein (LDL) are expected to attenuate atherosclerosis, yet not all antioxidants that inhibit LDL oxidation in vitro inhibit disease in animal models of atherosclerosis. As with animal studies, a benefit with dietary supplements of antioxidants in general and vitamin E in particular was anticipated in humans, yet the overall outcome of large, randomized controlled studies has been disappointing. However, in recent years it has become clear that the role of vitamin E in LDL oxidation and the relationship between in vitro and in vivo inhibition of LDL oxidation aremore complex than previously appreciated, and that oxidative events in addition to LDL oxidation in the extracellular space need to be considered in the contextof an antioxidant as a therapeutic drug against atherosclerosis. This review focuses on some of these complexities, proposes a novel method to assess in vitro ‘oxidizability’ of lipoprotein lipids, and summarizes the present situation of development of antioxidant compounds as drugs against atherosclerosis and related cardiovascular disorders.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 429.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 549.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 549.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Alho H, Leinonen J (1999) Total anti-oxidant activity measured by chemiluminescence methods. Methods Enzymol 299:3–15

    PubMed  Google Scholar 

  • Bird DA, Tangirala RK, Fruebis J, Steinberg D, Witztum JL, Palinski W (1998) Effect of probucol on LDL oxidation and atherosclerosis in LDL receptor deficient mice. J Lipid Res 39:1079–1090

    PubMed  Google Scholar 

  • Bjorkhem I, Henriksson-Freyschuss A, Breuer O, Diczfalusy U, Berglund L, Henriksson P (1991) The anti-oxidant butylated hydroxytoluene protects against atherosclerosis. Arterioscler Thromb 11:15–22

    PubMed  Google Scholar 

  • Böger, RH, Bode-Böger SM, Phivthong-ngam L, Brandes RP, Schwedhelm E, Mügge A, Böhme M, Tsikas D, Frölich JC (1998) Dietary L-arginine and α-tocopherol reduce vascular oxidative stress and preserve endothelial function in hypercholesterolemic rabbits via different mechanisms. Atherosclerosis 141:31–43

    PubMed  Google Scholar 

  • Boring, L, Gosling J, Cleary M, Charo IF (1998) Decreased lesion formation in CCR2-/-mice reveals a role for chemokines in the initiation of atherosclerosis. Nature 394:894–897

    PubMed  Google Scholar 

  • Bowry VW, Ingold KU (1999) The unexpected role of vitamin E (α-to copherol) in the peroxidation of human low-density lipoprotein. Acc Chem Res 32:27–34

    Article  Google Scholar 

  • Bowry VW, Ingold KU, Stocker R (1992) Vitamin E in human low-density lipoprotein. When and how this anti-oxidant becomes a pro-oxidant. Biochem J 288:341–344

    PubMed  Google Scholar 

  • Bowry VW, Mohr D, Cleary J, Stocker R (1995) Prevention of tocopherol-mediated peroxidation of ubiquinol-10-free human low density lipoprotein. J Biol Chem 270:5756–5763

    Article  PubMed  Google Scholar 

  • Bowry VW, Stocker R (1993) Tocopherol-mediated peroxidation. The pro-oxidant effect of vitamin E on the radical-initiated oxidation of human low-density lipoprotein. J Am Chem Soc 115:6029–6044

    Article  Google Scholar 

  • Brattsand R (1975) Actions of vitamins A and E and some nicotinic acid derivatives on plasma lipids and on lipid infiltration of aorta in cholesterol-fed rabbits. Atherosclerosis 22:47–61

    Article  PubMed  Google Scholar 

  • Bruger M (1945) Experimental Atherosclerosis. VII. Effect of vitamin E. Proc Soc Exp Biol Med 59:56–57

    Google Scholar 

  • Carew TE, Schwenke DC, Steinberg D (1987) Antiatherogenic effect of probucol unrelated to its hypocholesterolemic effect: evidence that anti-oxidants in vivo can selectively inhibit low density lipoprotein degradation in macrophage-rich fatty streaks and slow the progression of atherosclerosis in the Watanabe heritable hyperlipidemic rabbit. Proc Natl Acad Sci USA 84:7725–7729

    PubMed  Google Scholar 

  • Carr AC, McCall MR, Frei B (2000). Oxidation of LDL by myeloperoxidase and reactive nitrogen species: reaction pathways and anti-oxidant protection. Arterioscler Thromb Vasc Biol 20:1716–1723

    PubMed  Google Scholar 

  • Choy KJ, Deng YM, Hou JY, Wu B, Lau AK, Witting PK, Stocker R (2003) Coenzyme Q10 supplementation inhibits aortic lipid oxidation but fails to attenuate intimal thickening in balloon-injured New Zealand White rabbits. Free Radic Biol Med 35:300–309

    Article  PubMed  Google Scholar 

  • Culbertson SM, Vinqvist MR, Barclay LR, Porter NA (2001) Minimizing tocopherol-mediated radical phase transfer in low-density lipoprotein oxidation with an amphiphilic unsymmetrical azo initiator. J Am Chem Soc 123:8951–8960

    Article  PubMed  Google Scholar 

  • Cushing SD, Berliner JA, Valente AJ, Territo MC, Navab M, Parhami F, Gerrity R, Schwartz CJ, Fogelman AM (1990) Minimally modified low density lipoprotein induces monocyte chemotactic protein (MCP-1) in human endothelial and smooth muscle cells. Proc Natl Acad Sci USA 87:5134–5138

    PubMed  Google Scholar 

  • Cynshi O (1997) Preventives/remedies for arteriosclerosis. Patent WO9850025

    Google Scholar 

  • Cynshi O, Kawabe Y, Suzuki T, Takashima Y, Kaise H, Nakamura M, Ohba Y, Kato Y, Tamura K, Hayasaka A, Higashida A, Sakaguchi H, Takeya M, Takahashi K, Inoue K, Noguchi N, Niki E, Kodama T (1998) Antiatherogenic effects of the anti-oxidant BO-653 in three different animal models. Proc Natl Acad Sci USA 95:10123–10128

    Article  PubMed  Google Scholar 

  • Cynshi O, Stocker R (2003) Methods for evaluating anti-oxidant potency of biological samples. WO2004083869

    Google Scholar 

  • Cyrus T, Yao Y, Rokach J, Tang LX, Pratico D (2003) Vitamin E reduces progression of atherosclerosis in low-density lipoprotein receptor-deficient mice with established vascular lesions. Circulation 107:521–523

    Article  PubMed  Google Scholar 

  • Davi G, Alessandrini P, Mezzetti A, Minotti G, Bucciarelli T, Costantini F, Cipollone F, Bon GB, Ciabattoni G, Patrono C (1997) In vivo formation of 8-Epi-prostaglandin F2 alpha is increased in hypercholesterolemia. Arterioscler Thromb Vasc Biol 17:3230–3235

    PubMed  Google Scholar 

  • Davi G, Ciabattoni G, Consoli A, Mezzetti A, Falco A, Santarone S, Pennese E, Vitacolonna E, Bucciarelli T, Costantini F, Capani F, Patrono C (1999) In vivo formation of 8-iso-prostaglandin F2α and platelet activation in diabetes mellitus: effects of improved metabolic control and vitamin E supplementation. Circulation 99:224–229

    PubMed  Google Scholar 

  • Dieber-Rotheneder M, Puhl H, Waeg G, Striegl G, Esterbauer H (1991) Effect of oral supplementation with D-alpha-tocopherol on the vitamin E content of human low density lipoproteins and resistance to oxidation. J Lipid Res 32:1325–1332

    PubMed  Google Scholar 

  • Efe H, Deger O, Kirci D, Karahan SC, Orem A, Calapoglu M (1999) Decreased neutrophil antioxidative enzyme activities and increased lipid peroxidation in hyperlipoproteinemic human subjects. Clin Chim Acta 279:155–165

    Article  PubMed  Google Scholar 

  • Erl W, Weber C, Wardemann C, Weber PC (1997) α-Tocopheryl succinate inhibits monocytic cell adhesion to endothelial cells by suppressing NF-kappa B mobilization. AmJ Physiol 273: H634–H640

    Google Scholar 

  • Esterbauer H, Dieber-Rotheneder M, Striegl G, Waeg G (1991) Role of vitamin E in preventing the oxidation of low-density lipoprotein. Am J Clin Nutr 53:314S–321S

    PubMed  Google Scholar 

  • Esterbauer H, Gebicki J, Puhl H, Jürgens G (1992) The role of lipid peroxidation and antioxidants in oxidative modification of LDL. Free Radic Biol Med 13:341–390

    Article  PubMed  Google Scholar 

  • Esterbauer H, Jürgens G, Quehenberger O, Koller E (1987) Autoxidation of human low density lipoprotein: loss of polyunsaturated fatty acids and vitamin E and generation of aldehydes. J Lipid Res 28:495–509

    PubMed  Google Scholar 

  • Esterbauer H, Striegl G, Puhl H, Rotheneder M (1989) Continuous monitoring of in vitro oxidation of human low density lipoprotein. Free Rad Res Comms 6:67–75

    Google Scholar 

  • Freyschuss A, Stiko-Rahm A, Swedenborg J, Henriksson P, Bjorkhem I, Berglund L, Nilsson J (1993) Antioxidant treatment inhibits the development of intimal thickening after balloon injury of the aorta in hypercholesterolemic rabbits. J Clin Invest 91:1282–1288

    PubMed  Google Scholar 

  • Fruebis J, Steinberg D, Dresel HA, Carew TA (1994) A comparison of the antiatherogenic effects of probucol and a structural analogue of probucol in low density lipoprotein receptor-deficient rabbits. J Clin Invest 94:392–398

    PubMed  Google Scholar 

  • Garner B, Waldeck AR, Witting PK, Rye K-A, Stocker R (1998) Oxidation of high density lipoproteins. II. Evidence for direct reduction of HDL lipid hydroperoxides by methionine residues of apolipoproteins AI and AII. J Biol Chem 273:6088–6095

    Article  PubMed  Google Scholar 

  • Godfried SL, Combs GF, Saroka JM, Dillingham LA (1989) Potentiation of atherosclerotic lesions in rabbits by high dietary level of vitamin E. Br J Nutr 61:607–617

    Article  PubMed  Google Scholar 

  • Goldstein JL, Ho YK, Basu SK, Brown MS (1979) Binding site on macrophages that mediates uptake and degradation of acetylated low density lipoprotein, producing massive cholesterol deposition. Proc Natl Acad Sci USA 76:333–337

    PubMed  Google Scholar 

  • Gosling J, Slaymaker S, Gu L, Tseng S, Zlot CH, Young SG, Rollins BJ, Charo IF (1999) MCP-1 deficiency reduces susceptibility to atherosclerosis in mice that overexpress human apolipoprotein B. J Clin Invest 103:773–778

    PubMed  Google Scholar 

  • Griendling KK, FitzGerald GA (2003) Oxidative stress and cardiovascular injury: Part I: basic mechanisms and in vivo monitoring of ROS. Circulation 108:1912–1916

    Article  PubMed  Google Scholar 

  • Griffith RL, Virella GT, Stevenson HC, Lopes-Virella MF (1988) Low density lipoprotein metabolism by human macrophages activated with low density lipoprotein immune complexes. A possible mechanism of foam cell formation. J Exp Med 168:1041–1059

    PubMed  Google Scholar 

  • Haberland ME, Fogelman AM, Edwards PA (1982). Specificity of receptor-mediated recognition of malonydialdehyde-modified low density lipoproteins. Proc Natl Acad Sci USA 79:1712–1716

    PubMed  Google Scholar 

  • Haberland ME, Olch CL, Fogelman AM (1984) Role of lysines in mediating interaction of modified low density lipoproteins with the scavenger receptor of human monocyte macrophages. J Biol Chem 259:11305–11311

    PubMed  Google Scholar 

  • Hatch GM (2002) AGI-1067. AtheroGenics. Curr Opin Investig Drugs 3:433–436

    PubMed  Google Scholar 

  • Hazell LJ, Stocker R (1997) α-Tocopherol does not inhibit hypochlorite-induced oxidation of apolipoprotein B-100 of low-density lipoprotein. FEBS Lett 414:541–544

    PubMed  Google Scholar 

  • Henriksen T, Mahoney EM, Steinberg D (1981) Enhanced macrophage degradation of low density lipoprotein previously incubated with cultured endothelial cells: recognition by receptors for acetylated low density lipoproteins. Proc Natl Acad Sci USA 78:6499–6503

    PubMed  Google Scholar 

  • Hörkkö S, Bird DA, Miller E, Itabe H, Leitinger N, Subbanagounder G, Berliner JA, Friedman P, Dennis EA, Curtiss LK, Palinski W, Witztum JL (1999) Monoclonal autoantibodies specific for oxidized phospholipids or oxidized phospholipid-protein adducts inhibit macrophage uptake of oxidized low-density lipoproteins. J Clin Invest 103:117–128

    PubMed  Google Scholar 

  • Huang HY, Appel LJ, Croft KD, Miller ER, 3rd, Mori TA, Puddey IB (2002) Effects of vitamin C and vitamin E on in vivo lipid peroxidation: results of a randomized controlled trial. Am J Clin Nutr 76:549–555

    PubMed  Google Scholar 

  • Ingold KU, Bowry VW, Stocker R, Walling C (1993) Autoxidation of lipids and antioxidation by α-tocopherol and ubiquinol in homogeneous solution and in aqueous dispersions of lipids. The unrecognized consequences of lipid particle size as exemplified by the oxidation of human low density lipoprotein. Proc Natl Acad Sci USA 90:45–49

    PubMed  Google Scholar 

  • Inoue K, Cynshi O, Kawabe Y, Nakamura M, Miyauchi K, Kimura T, Daida H, Hamakubo T, Yamaguchi H, Kodama T (2002) Effect of BO-653 and probucol on c-MYC and PDGF-A messenger RNA of the iliac artery after balloon denudation in cholesterol-fed rabbits. Atherosclerosis 161:353–363

    Article  PubMed  Google Scholar 

  • Iwatsuki M, Niki E, Stone D, Darley-Usmar VM (1995) α-Tocopherol mediated peroxidation in the copper (II) and met myoglobin induced oxidation of human low density lipoprotein: the influence of lipid hydroperoxides. FEBS Lett 360:271–276

    Article  PubMed  Google Scholar 

  • Karmansky I, Shnaider H, Palant A, Gruener N (1996) Plasma lipid oxidation and susceptibility of low-density lipoproteins to oxidation in male patients with stable coronary artery disease. Clin Biochem 29:573–579

    Article  PubMed  Google Scholar 

  • Keaney JF, Jr, Gaziano JM, Xu A, Frei B, Curran-Celentano J, Shwaery GT, Loscalzo J, Vita JA (1994) Low-dose α-tocopherol improves and high-dose α-tocopherol worsens endothelial vasodilator function in cholesterol-fed rabbits. J Clin Invest 93:844–851

    PubMed  Google Scholar 

  • Kita T, Nagano Y, Yokode M, Ishii K, Kume N, Ooshima A, Yoshida H, Kawai C (1987) Probucol prevents the progression of atherosclerosis in Watanabe heritable hyperlipidemic rabbit, an animal model for familial hypercholesterolemia. Proc Natl Acad Sci USA 84:5928–5931

    PubMed  Google Scholar 

  • Klimov AN, Denisenko AD, Popov AV, Nagornev VA, Pleskov VM, Vinogradov AG, Denisenko TV, Magracheva E, Kheifes GM, Kuznetzov AS (1985) Lipoprotein-antibody immune complexes. Their catabolism and role in foam cell formation. Atherosclerosis 58:1–15

    PubMed  Google Scholar 

  • Kodama T, Freeman M, Rohrer L, Zabrecky J, Matsudaira P, Krieger M (1990) Type I macrophage scavenger receptor contains alpha-helical and collagen-like coiled coils. Nature 343:531–535

    PubMed  Google Scholar 

  • Kontush A, Finckh B, Karten B, Kohlschütter A, Beisiegel U (1996) Antioxidant and prooxidant activity of α-tocopherol in human plasma and low density lipoprotein. J Lipid Res 37:1436–1448

    PubMed  Google Scholar 

  • Kritchevsky D, Kim HK, Tepper SA (1971) Influence of 4,4′-(isopropylidenedithio)bis(2,6-di-t-butylphenol) (DH-581) on experimental atherosclerosis in rabbits. Proc Soc Exp Biol Med 136:1216–1221

    PubMed  Google Scholar 

  • Kritharides L, Jessup W, Gifford J, Dean RT (1993) A method for defining the stages of LDL oxidation by the separation of cholesterol and cholesteryl ester-oxidation products by HPLC. Anal Biochem 213:79–89

    Article  PubMed  Google Scholar 

  • Kritharides L, Stocker R (2002) The use of anti-oxidant supplements in coronary heart disease. Atherosclerosis 164:211–219

    PubMed  Google Scholar 

  • Lynch SM, Morrow JD, Roberts LJ, II, Frei B (1994) Formation of noncyclooxygenasederived prostanoids (F2-isoprostanes) in plasma and low-density lipoprotein exposed to oxidative stress in vitro. J Clin Invest 93:998–1004

    PubMed  Google Scholar 

  • Mao SJ, Yates MT, Parker RA, Chi EM, Jackson RL (1991) Attenuation of atherosclerosis in a modified strain of hypercholesterolemic Watanabe rabbits with use of a probucol analogue (MDL 29,311) that does not lower serum cholesterol. Arterioscler Thromb 11:1266–1275

    PubMed  Google Scholar 

  • Marshall FN (1982) Pharmacology and toxicology of probucol. Artery 10:7–21

    PubMed  Google Scholar 

  • Marui N, Offermann MK, Swerlick R, Kunsch C, Rosen CA, Ahmad M, Alexander RW, Medford RM (1993) Vascular cell adhesion molecule-1 (VCAM-1) gene transcription and expression are regulated through an anti-oxidant-sensitive mechanism in human vascular endothelial cells. J Clin Invest 92:1866–1874

    PubMed  Google Scholar 

  • Mashima R, Witting PK, Stocker R (2001) Oxidants and anti-oxidants in atherosclerosis. Curr Opin Lipidol 12:411–418

    PubMed  Google Scholar 

  • Mashima R, Yoshimura S, Yamamoto Y (1999) Reduction of lipid hydroperoxides by apolipoprotein B-100. Biochem Biophys Res Commun 259:185–189

    PubMed  Google Scholar 

  • McMurray HF, Parthasarathy S, Steinberg D (1993)Oxidatively modified low density lipoprotein is a chemoattractant for human T lymphocytes. J Clin Invest 92:1004–1008

    PubMed  Google Scholar 

  • Meagher EA, Barry OP, Lawson JA, Rokach J, FitzGerald G (2001) Effects of vitamin E on lipid peroxidation in healthy persons. JAMA 285:1178–1182

    Article  PubMed  Google Scholar 

  • Medford RM, Somers P (1997) Monoesters of probucol for the treatment of cardiovascular and inflammatory disease. WO9851289

    Google Scholar 

  • Medford RM, Somers PK, Hoong LK, Meng CQ (1997) Compounds and methods for the inhibition of the expression of VCAM-1. Patent WO9851662

    Google Scholar 

  • Meng CQ (2003) BO-653. Chugai. Curr Opin Investig Drugs 4:342–346

    PubMed  Google Scholar 

  • Miyauchi K, Schwartz RS, Aihara K, Kurata T, Sato H, Yamaguchi H, Daida H (2000) Efficacy of a novel anti-oxidant on vascular remodelling after coronary angioplasty: Possible role of endothelial function and collagen accumulation. Circulation 102:915 (Abstract)

    PubMed  Google Scholar 

  • Moghadasian MH, McManus BM, Godin DV, Rodrigues B, Frohlich JJ (1999) Proatherogenic and antiatherogenic effects of probucol and phytosterols in apolipoprotein E-deficient mice: possible mechanisms of action. Circulation 99:1733–1739

    PubMed  Google Scholar 

  • Morrow JD, Awad JA, Kato T, Takahashi K, Badr KF, Roberts LJ, 2nd, Burk RF (1992) Formation of novel non-cyclooxygenase-derived prostanoids (F2-isoprostanes) in carbon tetrachloride hepatotoxicity. An animal model of lipid peroxidation. J Clin Invest 90:2502–2507

    PubMed  Google Scholar 

  • Morrow JD, Frei B, Longmire AW, Gaziano JM, Lynch SM, Shyr Y, Strauss WE, Oates JA, Roberts LJ, 2nd. (1995) Increase in circulating products of lipid peroxidation (F2-isoprostanes) in smokers. Smoking as a cause of oxidative damage. N Engl J Med 332:1198–1203

    PubMed  Google Scholar 

  • Morrow JD, Hill KE, Burk RF, Nammour TM, Badr KF, Roberts LJ, 2nd (1990) A series of prostaglandin F2-like compounds are produced in vivo in humans by a noncyclooxygenase, free radical-catalyzed mechanism. Proc Natl Acad Sci USA 87:9383–9387

    PubMed  Google Scholar 

  • Morrow JD, Minton TA, Badr KF, Roberts LJ, 2nd (1994) Evidence that the F2-isoprostane, 8-epi-prostaglandin F2 alpha, is formed in vivo. Biochim Biophys Acta 1210:244–248

    PubMed  Google Scholar 

  • Mosca L, Rubenfire M, Mandel C, Rock C, Tarshis T, Tsai A, Pearson T (1997) Antioxidant nutrient supplementation reduces the susceptibility of low density lipoprotein to oxidation in patients with coronary artery disease. J Am Coll Cardiol 30:392–399

    Article  PubMed  Google Scholar 

  • Moses C, Rhodes GL, Levinson JP (1952) The effect of alpha-tocopherol on experimental aptherosclerosis. Angiology 3:397–407

    PubMed  Google Scholar 

  • Navab M, Imes SS, Hama SY, Hough GP, Ross LA, Bork RW, Valente AJ, Berliner JA, Drinkwater DC, Laks H, Fogelman AM (1991) Monocyte transmigration induced by modification of low density lipoprotein in cocultures of human aortic wall cells is due to induction of monocyte chemotactic protein 1 synthesis and is abolished by high density lipoprotein. J Clin Invest 88:2039–2046

    PubMed  Google Scholar 

  • Neuzil J, Witting PK, Stocker R (1997) α-Tocopheryl hydroquinone is an efficient multifunctional inhibitor of radical-initiated oxidation of low-density lipoprotein lipids. Proc Natl Acad Sci USA 94:7885–7890

    PubMed  Google Scholar 

  • Niu X, Zammit V, Upston JM, Dean RT, Stocker R (1999) Co-existence of oxidized lipids and α-tocopherol in all lipoprotein fractions isolated from advanced human atherosclerotic plaques. Arterioscler Thromb Vasc Biol 19:1708–1718

    PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  • Parker RA, Sabrah T, Cap M, Gill BT (1995) Relation of vascular oxidative stress, α-tocopherol, and hypercholesterolemia to early atherosclerosis in hamsters. Arterioscler Thromb Vasc Biol 15:349–358

    PubMed  Google Scholar 

  • Parthasarathy S, Young SG, Witztum JL, Pittman RC, Steinberg D (1986). Probucol inhibits oxidative modification of low density lipoprotein. J Clin Invest 77:641–644

    PubMed  Google Scholar 

  • Parums DV, Brown DL, Mitchinson MJ (1990) Serum antibodies to oxidized low-density lipoprotein and ceroid in chronic periaortitis. Arch Pathol Lab Med 114:383–387

    PubMed  Google Scholar 

  • Patrono C, FitzGerald GA (1997) Isoprostanes: potential markers of oxidant stress in atherothrombotic disease. Arterioscler Thromb Vasc Biol 17:2309–2315

    PubMed  Google Scholar 

  • Podrez EA, Poliakov E, Shen Z, Zhang R, Deng Y, Sun M, Finton PJ, Shan L, Febbraio M, Hajjar DP, Silverstein RL, Hoff HF, Salomon RG, Hazen SL (2002) A novel family of atherogenic oxidized phospholipids promotes macrophage foam cell formation via the scavenger receptor CD36 and is enriched in atherosclerotic lesions. J Biol Chem 277:38517–38523

    Article  PubMed  Google Scholar 

  • Podrez EA, Poliakov E, Shen Z, Zhang R, Deng Y, Sun M, Finton PJ, Shan L, Gugiu B, Fox PL, Hoff HF, Salomon RG, Hazen SL (2002) Identification of a novel family of oxidized phospholipids that serve as ligands for the macrophage scavenger receptor CD36. J Biol Chem 277:38503–38516

    Article  PubMed  Google Scholar 

  • Prasad K, Kalra J (1993) Oxygen free radicals and hypercholesterolemic atherosclerosis: effect of vitamin E. Am Heart J 125:958–973

    PubMed  Google Scholar 

  • Pratico D, Tangirala RK, Radar D, Rokach J, FitzGerald GA (1998) Vitamin E suppresses isoprostane generation in vivo and reduces atherosclerosis in apoE-deficient mice. Nat Med 4:1189–1192

    Article  PubMed  Google Scholar 

  • Pryor WA, Cornicelli JA, Devall LJ, Tait B, Trivedi BK, Witiak DT, Wu M (1993) A rapid screening test to determine the anti-oxidant potencies of natural and synthetic antioxidants. J Org Chem 58:3521–3532

    Google Scholar 

  • Qiao Y, Yokoyama M, Kameyama K, Asano G (1993) Effect of vitamin E on vascular integrity in cholesterol-fed guinea pigs. Arterioscl Thromb 13:1885–1892

    PubMed  Google Scholar 

  • Quinn MT, Parthasarathy S, Fong LG, Steinberg D (1987) Oxidatively modified low density lipoproteins: a potential role in recruitment and retention of monocyte/macrophages during atherogenesis. Proc Natl Acad Sci USA 84:2995–2998

    PubMed  Google Scholar 

  • Quinn MT, Parthasarathy S, Steinberg D (1985) Endothelial cell-derived chemotactic activity for mouse peritoneal macrophages and the effects of modified forms of low density lipoprotein. Proc Natl Acad Sci USA 82:5949–5953

    PubMed  Google Scholar 

  • Rajavashisth TB, Andalibi A, Territo MC, Berliner JA, Navab M, Fogelman AM, Lusis AJ (1990) Induction of endothelial cell expression of granulocyte and macrophage colony-stimulating factors by modified low-density lipoproteins. Nature 344:254–257

    PubMed  Google Scholar 

  • Reaven PD, Parthasarathy S, Beltz WF, Witztum JL (1992) Effect of probucol dosage on plasma lipid and lipoprotein levels and on protection of low density lipoprotein against in vitro oxidation in humans. Arterioscler Thromb 12:318–324

    PubMed  Google Scholar 

  • Reilly M, Delanty N, Lawson JA, FitzGerald GA (1996) Modulation of oxidant stress in vivo in chronic cigarette smokers. Circulation 94:19–25

    PubMed  Google Scholar 

  • Rice-Evans C, Miller NJ (1994) Total anti-oxidant status in plasma and body fluids. Methods Enzymol 234:279–293

    PubMed  Google Scholar 

  • Salonen JT, Ylä-Herttuala S, Yamamoto R, Butler S, Korpela H, Salonen R, Nyyssönen K, Palinski W, Witztum JL (1992) Autoantibody against oxidised LDL and progression of carotid atherosclerosis. Lancet 339:883–887

    Article  PubMed  Google Scholar 

  • Santanam N, Penumetcha M, Speisky H, Parthasarathy S (2004) A novel alkaloid antioxidant, Boldine and synthetic anti-oxidant, reduced form of RU486, inhibit the oxidation of LDL in-vitro and atherosclerosis in vivo in LDLR(-/-) mice. Atherosclerosis 173:203–210

    PubMed  Google Scholar 

  • Sasahara M, Raines EW, Chait A, Carew TE, Steinberg D, Wahl PW, Ross R (1994) Inhibition of hypercholesterolemia-induced atherosclerosis in the nonhuman primate by probucol. I. Is the extent of atherosclerosis related to resistance of LDL to oxidation? J Clin Invest 94:155–164

    PubMed  Google Scholar 

  • Sawayama Y, Shimizu C, Maeda N, Tatsukawa M, Kinukawa N, Koyanagi S, Kashiwagi S, Hayashi J (2002) Effects of probucol and pravastatin on common carotid atherosclerosis in patients with asymptomatic hypercholesterolemia. Fukuoka Atherosclerosis Trial (FAST). J Am Coll Cardiol 39:610–616

    PubMed  Google Scholar 

  • Shaish A, Daugherty A, O'sullivan F, Schonfeld G, Heinecke JW (1995) Beta-carotene inhibits atherosclerosis in hypercholesterolemic rabbits. J Clin Invest 96:2075–2082

    PubMed  Google Scholar 

  • Sparrow CP, Doebber TW, Olszewski J, Wu MS, Ventre J, Stevens KA, Chao YS (1992) Low density lipoprotein is protected from oxidation and the progression of atherosclerosis is slowed in cholesterol-fed rabbits by the anti-oxidant N,N′-diphenyl-phenylenediamine. J Clin Invest 89:1885–1891

    PubMed  Google Scholar 

  • Steinberg D, Parthasarathy S, Carew TE, Khoo JC, Witztum JL (1989) Beyond cholesterol: Modifications of low-density lipoprotein that increase its atherogenicity. N Engl J Med 320:915–924

    PubMed  Google Scholar 

  • Steinbrecher UP, Lougheed M, Kwan W-C, Dirks M (1989) Recognition of oxidized low density lipoprotein by the scavenger receptor of macrophages results from derivatization of apolipoprotein B by products of fatty acid peroxidation. J Biol Chem 264:15216–15223

    PubMed  Google Scholar 

  • Steinbrecher UP, Parthasarathy S, Leake DS, Witztum JL, Steinberg D (1984) Modification of low density lipoprotein by endothelial cells involves lipid peroxidation and degradation of low density lipoprotein phospholipids. Proc Natl Acad Sci USA 81:3883–3887

    PubMed  Google Scholar 

  • Stocker R (1999) The ambivalence of vitamin E in atherogenesis. TiBS 24:219–223

    PubMed  Google Scholar 

  • Stocker R (1999) Dietary and pharmacological anti-oxidants in atherosclerosis. Curr Opin Lipidol 10:589–597

    Article  PubMed  Google Scholar 

  • Stocker R, Bowry VW, Frei B (1991) Ubiquinol-10 protects human low density lipoprotein more efficiently against lipid peroxidation than does α-tocopherol. Proc Natl Acad Sci USA 88:1646–1650

    PubMed  Google Scholar 

  • Stocker R, Keaney JF, Jr (2004) The role of oxidative modifications in atherosclerosis. Physiol Rev 84:1381–1478

    Article  PubMed  Google Scholar 

  • Suarna C, Dean RT, May J, Stocker R (1995) Human atherosclerotic plaque contains both oxidized lipids and relatively large amounts of α-tocopherol and ascorbate. Arterioscler Thromb Vasc Biol 15:1616–1624

    PubMed  Google Scholar 

  • Sun J, Giraud DW, Moxley RA, Driskell JA (1997) β-Carotene and α-tocopherol inhibit the development of atherosclerotic lesions in hypercholesterolemic rabbits. Int J Vitam Nutr Res 67:155–163

    PubMed  Google Scholar 

  • Sundell CL, Somers PK, Meng CQ, Hoong LK, Suen KL, Hill RR, Landers LK, Chapman A, Butteiger D, Jones M, Edwards D, Daugherty A, Wasserman MA, Alexander RW, Medford RM, Saxena U (2003) AGI-1067: a multifunctional phenolic anti-oxidant, lipid modulator, anti-inflammatory and antiatherosclerotic agent. J Pharmacol Exp Ther 305:1116–1123

    Article  PubMed  Google Scholar 

  • Suzuki H, Kurihara Y, Takeya M, Kamada N, Kataoka M, Jishage K, Ueda O, Sakaguchi H, Higashi T, Suzuki T, Takashima Y, Kawabe Y, Cynshi O, Wada Y, Honda M, Kurihara H, Aburatani H, Doi T, Matsumoto A, Azuma S, Noda T, Toyoda Y, Itakura H, Yazaki Y, Horiuchi S, Takahashi K, Kruijt JK, van Berkel TJC, Steinbrecher UP, Ishibashi S, Maeda N, Gordon S, Kodama T (1997) A role for macrophage scavenger receptors in atherosclerosis and susceptibility to infection. Nature 386:292–296

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  • Tangirala RK, Casanada F, Miller E, Witztum JL, Steinberg D, Palinski W (1995) Effect of the anti-oxidant N,N′-diphenyl 1,4-phenylenediamine (DPPD) on atherosclerosis in apoE-deficient mice. J Lipid Res 15:1625–1630

    Google Scholar 

  • Tardif J-C, Côté G, Lespérance J, Bourassa M, Lambert J, Doucet S, Bilodeau L, Nattel S, de Guise P (1997) Probucol and multivitamins in the prevention of restenosis after coronary angioplasty. N Engl J Med 337:365–372

    Article  PubMed  Google Scholar 

  • Tardif JC, Gregoire J, Schwartz L, Title L, Laramee L, Reeves F, Lesperance J, Bourassa MG, L'Allier PL, Glass M, Lambert J, Guertin MC (2003) Effects of AGI-1067 and probucol after percutaneous coronary interventions. Circulation 107:552–558

    Article  PubMed  Google Scholar 

  • Tawara K, Ishihara M, Ogawa H, Tomikawa M (1986) Effect of probucol, pantethine and their combinations on serum lipoprotein metabolism and on the incidence of atheromatous lesions in the rabbit. Jpn J Pharmacol 41:211–222

    PubMed  Google Scholar 

  • Terentis AC, Thomas SR, Burr JA, Liebler DC, Stocker R (2002) Vitamin E oxidation in human atherosclerotic lesions. Circ Res 90:333–339

    Article  PubMed  Google Scholar 

  • Thomas SR, Davies MJ, Stocker R (1998) Oxidation and antioxidation of human low-density lipoprotein and plasma exposed to 3-morpholinosydnonimine and reagent peroxynitrite. Chem Res Toxicol 11:484–494

    Article  PubMed  Google Scholar 

  • Thomas SR, Leichtweis SB, Pettersson K, Croft KD, Mori TA, Brown AJ, Stocker R (2001) Dietary co-supplementation with vitamin E and coenzyme Q10 inhibits atherosclerosis in apolipoprotein E gene knockout mice. Arterioscler Thromb Vasc Biol 21:585–593

    PubMed  Google Scholar 

  • Thomas SR, Witting PK, Stocker R (1996) 3-Hydroxyanthranilic acid is an efficient, cell-derived co-anti-oxidant for α-tocopherol, inhibiting human low density lipoprotein and plasma lipid peroxidation. J Biol Chem 271:32714–32721

    Article  PubMed  Google Scholar 

  • Upston JM, Niu X, Brown AJ, Mashima R, Wang H, Senthilmohan R, Kettle AJ, Dean RT, Stocker R (2002) Disease stage-dependent accumulation of lipid and protein oxidation products in human atherosclerosis. Am J Pathol 160:701–710

    PubMed  Google Scholar 

  • Upston JM, Terentis AC, Morris K, Keaney JF, Jr., Stocker R (2002) Oxidized lipid accumulates in the presence of a-tocopherol in atherosclerosis. Biochem J 363:753–760

    Article  PubMed  Google Scholar 

  • Upston JM, Terentis AC, Stocker R (1999) Tocopherol-mediated peroxidation (TMP) of lipoproteins: implications for vitamin E as a potential antiatherogenic supplement. FASEB J 13:977–994

    PubMed  Google Scholar 

  • Upston JM, Witting PK, Brown AJ, Stocker R, Keaney JF, Jr. (2001) Effect of vitamin E on aortic lipid oxidation and intimal proliferation after vascular injury in cholesterol-fed rabbits. Free Radic Biol Med 31:1245–1253

    Article  PubMed  Google Scholar 

  • Walldius G, Olsson AG, Bergstrand L, Hadell K, Johansson J, Kaijser L, Lassvik C, Molgaard J, Nilsson S, et al. (1994) The effect of probucol on femoral atherosclerosis: the Probucol Quantitative Regression Swedish Trial (PQRST). Am J Cardiol 74:875–883

    Article  PubMed  Google Scholar 

  • Wang Z, Ciabattoni G, Créminon C, Lawson J, FitzGerald GA, Patrono C, Maclouf J (1995) Immumologival characterization of urinary 8-epi-prostaglandin F2α excretion in man. J Pharmacol Exp Therapeutics 275:94–100

    Google Scholar 

  • Wasserman MA, Sundell CL, Kunsch C, Edwards D, Meng CQ, Medford RM (2003) Chemistry and pharmacology of vascular protectants: a novel approach to the treatment of atherosclerosis and coronary artery disease. Am J Cardiol 91:34A–40A

    Article  PubMed  Google Scholar 

  • Wayner DDM, Burton GM, Ingold KU, Locke S (1985) Quantitative measurement of the total, peroxyl radical-trapping anti-oxidant capability of human blood plasma by controlled peroxidation. FEBS Lett 187:33–37

    Article  PubMed  Google Scholar 

  • Westrope KL, Miller RA, Wilson RB (1982) Vitamin E in a rabbit model of endogenous hypercholesterolemia and atherosclerosis. Nutr Rep Int 25:83–88

    Google Scholar 

  • Wissler RW, Vesselinovitch D (1983) Combined effects of cholestyramine and probucol on regression of atherosclerosis in rhesus monkey aortas. Appl Pathol 1:89–96

    PubMed  Google Scholar 

  • Witting PK, Pettersson K, Letters J, Stocker R (2000) Anti-atherogenic effect of coenzyme Q10 in apolipoprotein E gene knockout mice. Free Radic Biol Med 29:295–305

    Article  PubMed  Google Scholar 

  • Witting PK, Pettersson K, Letters J, Stocker R (2000) Site-specific anti-atherogenic effect of probucol in apolipoprotein E deficient mice. Arterioscler Thromb Vasc Biol 20: e26–e33

    PubMed  Google Scholar 

  • Witting PK, Pettersson K, Östlund-Lindqvist A-M, Westerlund C, Wågberg M, Stocker R (1999) Dissociation of atherogenesis from aortic accumulation of lipid hydro(pero)xides in Watanabe heritable hyperlipidemic rabbits. J Clin Invest 104:213–220

    PubMed  Google Scholar 

  • Witting PK, Pettersson K, Östlund-Lindqvist A-M, Westerlund C, Westin Eriksson A, Stocker R (1999) Inhibition by a co-anti-oxidant of aortic lipoprotein lipid peroxidation and atherosclerosis in apolipoprotein E and low density lipoprotein receptor gene double knockout mice. FASEB J 13:667–675

    PubMed  Google Scholar 

  • Witting PK, Upston JM, Stocker R (1997) The role of α-tocopheroxyl radical in the initiation of lipid peroxidation in human low density lipoprotein exposed to horse radish peroxidase. Biochemistry 36:1251–1258

    Article  PubMed  Google Scholar 

  • Witting PK, Upston JM, Stocker R (1998) Themolecular action of α-to copherol in lipoprotein lipid peroxidation: pro-and anti-oxidant activity of vitamin E in complex heterogeneous lipid emulsions. In: Quinn PJ, Kagan VE (eds) Subcellular biochemistry: fat-soluble vitamins. Plenum Press, London, pp 345–390

    Google Scholar 

  • Witting PK, Westerlund C, Stocker R (1996) A rapid and simple screening test for potential inhibitors of tocopherol-mediated peroxidation of LDL lipids. J Lipid Res 37:853–867

    PubMed  Google Scholar 

  • Yagi K (1984) Assay for blood plasma or serum. Methods Enzymol 105:328–331

    PubMed  Google Scholar 

  • Yamamoto Y, Ames BN (1987) Detection of lipid hydroperoxides and hydrogen peroxide at picomole levels by an HPLC and isoluminol chemiluminescence assay. Free Rad Biol Med 3:359–361

    PubMed  Google Scholar 

  • Yamamoto Y, Niki E (1989) Presence of cholesteryl ester hydroperoxide in human blood plasma. Biochem Biophys Res Comm 165:988–993

    Article  PubMed  Google Scholar 

  • Yeo HC, Helbock HJ, Chyu DW, Ames BN (1994) Assay of malondialdehyde in biological fluids by gas chromatography-mass spectrometry. Anal Biochem 220:391–396

    Article  PubMed  Google Scholar 

  • Zamburlini A, Maiorino M, Barbera P, Roveri A, Ursini F (1995) Direct measurement by single photon counting of lipid hydroperoxides in human plasma and lipoproteins. Anal Biochem 232:107–113

    Article  PubMed  Google Scholar 

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

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Fuji-Gotemba Research Laboratories, Chugai Pharmaceutical Co. Ltd, 1-135 Komakado, 412-8513, Gotemba, Shizuoka, Japan

    O. Cynshi

  2. Centre for Vascular Research, School of Medical Sciences, Faculty of Medicine, University of New SouthWales, 2052, Sydney, NSW, Australia

    R. Stocker

Authors
  1. O. Cynshi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R. Stocker
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Institute of Clinical Chemistry, University Hospital of Zurich, Rämistrasse 100, 8091, Zürich, Switzerland

    Arnold von Eckardstein

Rights and permissions

Reprints and permissions

Copyright information

© 2005 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Cynshi, O., Stocker, R. (2005). Inhibition of Lipoprotein Lipid Oxidation. In: von Eckardstein, A. (eds) Atherosclerosis: Diet and Drugs. Handbook of Experimental Pharmacology, vol 170. Springer, Berlin, Heidelberg. https://doi.org/10.1007/3-540-27661-0_21

Download citation

Publish with us

Policies and ethics

Search

Navigation