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Inhibition of LDL oxidation by antioxidants

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Free Radicals and Aging

Part of the book series: EXS ((EXS,volume 62))

Summary

Low density lipoprotein (LDL) consists of about 3000 fatty acids (50% polyunsaturated) and a single molecule apolipoprotein B (500 kDa). The endogenous antioxidants of LDL consist mainly of tocopherols and few carotenoids, which protect the PUFAS against oxidation. That native LDL contains traces of oxidation products has not been proved yet.

Oxidatively modified LDL (oLDL) exhibits cytotoxic and chemotactic activities, furthermore it leads to foam cell formation, a critical step in atherogenesis. The oxidation of LDL is a free radical process and leads to various aldehydic products. The oxidation of LDL is initiated by cells as well as by transition metals like Cu2+. In both cases the oxidation goes through three consecutive phases. The lag-phase is characterized by minimal degradation of PUFAs but a loss of the antioxidants. Thereafter the PUFAs are oxidized to lipid hydroperoxides, which are only intermediates (propagation-phase). These intermediates will decompose to aldehydic products, accompanied by several additional changes in the LDL particle (decomposition-phase). For increased macrophage uptake oLDL must reach the late decomposition-phase; the presence of lipid hydroperoxides in LDL is not sufficient. It is suggested that binding of aldehydes to free amino groups of Apo B is the reason for macrophage uptake. This is supported by the finding that antibodies against aldehyde-modified LDL are able to recognize oxidized LDL in atherosclerotic lesions. Antioxidants like α-tocopherol are able to protect LDL against oxidation. The duration of the lag-phase shows a linear relationship with the content of α-tocopherol in LDL. Yet the efficiency of α-tocopherol to protect LDL shows strong individual variation.

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References

  • Avogaro, P., Bittolo-Bon, G., and Cazzolato, G. (1988) Presence of a modified low density lipoprotein in humans. Arteriosclerosis 8: 79–87.

    Article  PubMed  CAS  Google Scholar 

  • Bedwell, S., Dean, R. T., and Jessup, W. (1989) The action of defined oxygen-centred free radical on human low-density lipoprotein. Biochem. J. 262: 707–712.

    PubMed  CAS  Google Scholar 

  • Boscoboinik, D., Szewczyk, A., Hensey, C., and Azzi, A. (1991) Inhibition of cell prohferation by a-tocopherol. J. Biol. Chem. 266: 6188–6194.

    PubMed  CAS  Google Scholar 

  • Carew, T. E., Schwenke, D. C., and Steinberg, D. (1987) Antiatherogenic effect of probucal unrelated to its hypocholesterolemic effect: evidence that antioxidants in vivo can selectively inhibit low density hpoprotein 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.

    Article  PubMed  CAS  Google Scholar 

  • Cazzolato, G., Avogaro, P., and Bittolo-Bon, G. (1991) Characterization of a more electroneg- atively charged LDL subfraction by ion exchange HPLC. Free Rad. Biol. Med. 11: 247–253.

    Article  PubMed  CAS  Google Scholar 

  • Curzio, M., Esterbauer, H., Di Mauro, C., Cecchini, G., and Dianzani, M. U. (1986) Chemotactic activity of the Hpid peroxidation product 4-hydroxynonenal and homologous hydroxyalkenals. Biol. Chem. Hoppe-Seyler 367: 321–329.

    Article  PubMed  CAS  Google Scholar 

  • Dieber-Rotheneder, M., Puhl, H., Wäg, G., Striegl, G., and Esterbauer, H. (1991) Effect of oral supplementation with d-alpha-tocopherol on the vitamin E content of human low density lipoproteins and its oxidation resistance. J. Lipid Res. 8: 1325–1332.

    Google Scholar 

  • Esterbauer, H., Juergens, G., Quehenberger, O., and 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  CAS  Google Scholar 

  • Esterbauer, H., Quehenberger, O., and Juergens, G. (1988) Oxidation of human low density lipoprotein with special attention to aldehydic lipid peroxidation products, in: Free Radicals: Methodology and Concepts, pp. 243–268.

    Google Scholar 

  • Eds C. Rice-Evans and B. Halliwell. Richelieu Press, London.

    Google Scholar 

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

    Article  CAS  Google Scholar 

  • Esterbauer, H., Zollner, H., and Schaur, R. J. (1989b) Aldehydes formed by lipid peroxidation: Mechanism of formation, occurrence and determination, in: Membrane Lipid Oxidation, vol. 1, pp. 239–268.

    Google Scholar 

  • Ed. C. Vigo-Pelfrey. CRC Press, Boca Raton.

    Google Scholar 

  • Esterbauer, H., Rotheneder, M., Waeg, G., Striedl, G., and Juergens, G. (1990a) Biochemical, structural, and functional properties of oxidized low-density lipoproteins. Chem. Res. Toxicol. 3: 77–92.

    Article  PubMed  CAS  Google Scholar 

  • Esterbauer, H., Dieber-Rotheneder, M., Waeg, G., Puhl, H., and Tatzber, F. (1990b) Endogenous antioxidants and lipoprotein oxidation. Biochem. Soc. Trans. 18: 1059–1061.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Esterbauer, H., Schaur, R. J., and Zollner, H. (1991b) Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes. Free Rad. Biol. Med. 11: 81–128.

    Article  PubMed  CAS  Google Scholar 

  • Esterbauer, H., Puhl, H., Dieber-Rotheneder, M., Waeg, G., and Rabl, H. (1991c) Effect of antioxidants on oxidative modification of LDL. Ann. Med. 23: 574–581.

    Article  Google Scholar 

  • Gaziano, J. M., Manson, J. E., Ridker, P. M., Buring, J. E., and Hennekens, C. H. (1990) Beta carotene for chronic stable angina. Circulation 82 (4 Suppl. Ill): 202.

    Google Scholar 

  • Gey, K. F., and Puska, P. (1989) Plasma vitamins E and A inversely related to mortality from ischemic heart disease in cross-cultural epidemiology. Ann. N.Y. Acad. Sci. 570: 268–282.

    Article  PubMed  CAS  Google Scholar 

  • Gey, F., Puska, P., Jordan, P., and Moser, U. K. (1991) Inverse correlation between plasma vitamin E and mortality from ischemic heart disease in cross-cultural epidemiology. Am. J. CHn. Nutr. 53: 326S-334S.

    CAS  Google Scholar 

  • Haberland, M. E., Fogelman, A. M., and Edwards, P. A. (1982) Specificity of receptor-medi- ated recognition of malondialdehyde-modified low density lipoprotein. Proc. Natl. Acad. Sci. USA 79: 1712–1716.

    Article  PubMed  CAS  Google Scholar 

  • Haberland, M. E., Fong, D., and Cheng, L. (1988) Malondialdehyde-altered protein occurs in atheroma of Watanabe heritable hyperlipidemic rabbits. Science 241: 215–218.

    Article  PubMed  CAS  Google Scholar 

  • Harats, D., Ben-Naim, M., Dabach, Y., Hollander, G., Stein, O., and Stein, Y. (1989) Cigarette smoking renders LDL susceptible to peroxidative modification and enhanced metabolism by macrophages. Atherosclerosis 79: 245–252.

    Article  PubMed  CAS  Google Scholar 

  • Hoff, H. F., Chisolm, G. M. Ill, Morel, D. W., Juergens, G., and Esterbauer, H. (1988) Chemical and functional changes in LDL following modification by 4-hydroxynonenal, in: oxy-Radicals Molecular Biology and Pathology, pp. 459–472.

    Google Scholar 

  • Eds P. A. Cerutti, J. M. McCord and T. Fridovich. Alan R. Liss, New York.

    Google Scholar 

  • Hoff, H. F., O’Neil, J., Chisolm, G. M., Cole, T. B., Quehenberger, O., Esterbauer, H., and Juergens, G. (1989) Modification of low-density lipoprotein with 4-hydroxynonenal induces uptake by macrophages. Arteriosclerosis 9: 538–549.

    Article  PubMed  CAS  Google Scholar 

  • Janero, D. R. (1991) Therapeutic potential of vitamin E in the pathogenesis of spontaneous athersclerosis. Free Rad. Biol. Med. 11: 129–144.

    Article  PubMed  CAS  Google Scholar 

  • Jessup, W., Rankin, S. M., De Whalley, C. V., Hoult, J. R. S., Scott, J., and Leake, D. S. (1990) Alpha-tocopherol consumption during low-density Hpoprotein oxidation. Biochem. J. 265: 399–405.

    PubMed  CAS  Google Scholar 

  • Juergens, G., Hoff, H. F., Chisolm, G. M., and Esterbauer, H. (1987) Modification of human serum low density lipoprotein by oxidation-characterization and pathophysiological implications. Chem. Phys. Lipids. 45: 315–336.

    Article  CAS  Google Scholar 

  • Juergens, G., Ashy, A., and Esterbauer, H. (1990) Detection of new epitopes formed upon oxidation of low-density lipoprotein, lipoprotein (a) and very-low-density lipoprotein. Use of an antiserum against 4-hydroxynonenal-modified low-density lipoprotein. Biochem. J. 265: 605–608.

    CAS  Google Scholar 

  • Kaneko, T., Kaji, K., and Matsuo, M. (1988) Cytotoxicities of a linoleic acid hydroperoxide and its related aliphatic aldehydes toward cultured human umbilical vein endothelial cells. Chem.-Biol. Interact. 67: 295–304.

    Article  PubMed  CAS  Google Scholar 

  • Kita, T., Nagano, Y., Yokode, M., Ishii, K., Kume, N., Narumiya, S., and Kawai, C. (1988) Prevention of atherosclerotic progession in Watanabe rabbits by probucol. Am. J. Cardiol. 62: 13B-19B.

    Article  PubMed  CAS  Google Scholar 

  • Liu, S. K., Dolensek, E. P., and Tappe, J. P. (1984) Cardiomyopathy associated with vitamin E deficiency in seven gelada baboons. J. Am. Vet. Med. Assoc. 185: 1347–1350.

    PubMed  CAS  Google Scholar 

  • Mino, M., Miki, M., Miyake, M., and Ogihara, T. (1989) Nutritional assessment of vitamin E in oxidative stress. Ann. N.Y. Acad. Sci. 570: 296–310.

    Article  PubMed  CAS  Google Scholar 

  • Morel, D. W., DiCorleto, P. E., and Chisolm, G. M. (1984) Endothelial and smooth muscle cells alter low density hpoprotein in vitro by free radical oxidation. Arteriosclerosis 4: 357–364.

    Article  PubMed  CAS  Google Scholar 

  • Morel, D. W., and Chisolm, G. M. (1989) Antioxidant treatment of diabetic rats inhibits Hpoprotein oxidation and cytotoxicity. J. Lipid Res. 30: 1827–1834.

    PubMed  CAS  Google Scholar 

  • Palinski, W., Rosenfeld, M. E., Ylä-Herttuala, S., Gurtner, G. C., Socher, S. S., Butler, S. W., Parthasarathy, S., Carew, T. E., Steinberg, D., and Witztum, J. L. (1989) Low density Hpoprotein undergoes oxidative modification in vivo. Proc. Natl. Acad. Sci. USA 86: 1372–1376.

    Article  PubMed  CAS  Google Scholar 

  • Parthasarathy, S., Young, S. G., Witztum, J. L., Pittman, R. C., and Steinberg, D. (1986) Probucol inhibits oxidative modification of low density Hpoprotein. J. CHn. Invest. 7: 641–644.

    Article  Google Scholar 

  • Quinn, M. T., Parthasarathy, S., Fong, L. G., and Steinberg, D. (1987) Oxidatively modified low density Hpoproteins: A potential role in recruitment and retention of monocyte/ macrophages during atherogenesis. Proc. Natl. Acad. Sci. USA 84: 2995–2998.

    Article  PubMed  CAS  Google Scholar 

  • Riemersma, R. A., Wood, D. A., Macintyre, C. C. A., Elton, R. A., Gey, K. F., and Oliver, M. F. (1991) Risk of angina pectoris and plasma concentrations of vitamins A, C and E and carotene. Lancet 337: 1–5.

    Article  PubMed  CAS  Google Scholar 

  • Rosenfeld, M. E., PaHnski, W., Ylä-Herttuala, S., Butler, S., and Witztum, J. L. (1990) Distribution of oxidation specific Hpid-protein adducts and apolipoprotein B in atherosclerotic lesions of varying severity from WHHL rabbits. Arteriosclerosis 10: 336–349.

    Article  PubMed  CAS  Google Scholar 

  • Smith, T. L., and Kummerow, F. A. (1989) Effect of dietary vitamin E on plasma Hpids and atherogenesis in restricted ovulatory chickens. Atherosclerosis 75: 105–109.

    CAS  Google Scholar 

  • Steinberg, D., Parthasarathy, S., Carew, T. E., Khoo, J. C., and Witztum, J. L. (1989) Beyond cholesterol. Modifications of low-density Hpoprotein that increase its atherogenicity. J. Engl. J. Med. 302: 915–924.

    Google Scholar 

  • Steinbrecher, U. P., Parathasarathy, S., Leake, D. S., Witztum J. L., and Steinberg, D. (1984) Modification of low density Hpoprotein by endothelial cells involves Hpid peroxidation and degradation of low density Hpoprotein phospholipids. Proc. Natl. Acad. Sci. USA 81: 3883–3887.

    Google Scholar 

  • Steinbrecher, U. P. (1987) Oxidation of human low density Hpoprotein results in derivatisa- tion of lysine residues of apolipoprotein B by Hpid peroxide decomposition products. J. Biol. Chem. 262: 3603–3608.

    PubMed  CAS  Google Scholar 

  • Steinbrecher, U. P., Zhang, H., and Lougheed, M. (1990) Role of oxidatively modified LDL in atherosclerosis. Free Rad. Biol. Med. 9: 155–168.

    Article  PubMed  CAS  Google Scholar 

  • Stocker, R., Bowry, V. W., and Frei, B. (1991) Ubiquinol-10 protects human low density Hpoprotein more efficiently against Hpid peroxidation than does a-tocopherol. Proc. Natl. Acad. Sci. USA 88: 1646–1650.

    Article  PubMed  CAS  Google Scholar 

  • Tolonen, M., Sarna, S., Halme, M., Tuominen, S. E. J., Westermarck, T., Nordberg, U., Keinonen, M., and Schrijer, J. (1988) Antioxidant supplementation decreases TBA reac- tants in serum of elderly. Biol. Trace Element Res. 17: 221–228.

    Article  CAS  Google Scholar 

  • Veriangieri, A. J., and Bush, M. J. (1992) Eff’ects of d-alpha-tocopherol supplementation on experimentally induced primate atherosclerosis. J. Am. Coll. Nutr. 11: 131–138.

    Google Scholar 

  • Weitzel, G., Schön, H., Gey, K. F., and Buddecke, E. (1956) Lipid-soluble vitamins and atherosclerosis. Hoppe Seylers Z. Physiol. Chem. 304: 247–72

    Article  CAS  Google Scholar 

  • Westrope, K. L., Miller, R. A., and Wilson, R. B. (1982) Vitamin E in a rabbit model of endogenous hypercholesterolemia and atherosclerosis. Nutr. Reports Int. 25: 83–88.

    CAS  Google Scholar 

  • Wilson, R. B., Middleton, C. C., and Sun, G. Y. (1978) Vitamin E antioxidants and Hpid peroxidation in experimental atherosclerosis of rabbits. J. Nutr. 108: 1858–67.

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Institute of Biochemistry, University of Graz, A-8010, Graz, Austria

    Hermann Esterbauer, Georg Waeg, Herbert Puhl, M. Dieber-Rotheneder & Franz Tatzber

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  1. Hermann Esterbauer
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  2. Georg Waeg
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  3. Herbert Puhl
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  4. M. Dieber-Rotheneder
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  5. Franz Tatzber
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Editors and Affiliations

  1. C.N.R.S., Institut Biomédical des Cordeliers, Université Pierre et Marie Curie, 15–21, Rue de l’Ecole de Médecine, F-75006, Paris, France

    Ingrid Emerit (Directeur de Recherche) (Directeur de Recherche)

  2. Department of Biochemistry and Biophysics, University of Pennsylvania, D-501 Richards Building, 19104-6089, Philadelphia, PA, USA

    Britton Chance

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© 1992 Birkhäuser Verlag Basel/Switzerland

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Esterbauer, H., Waeg, G., Puhl, H., Dieber-Rotheneder, M., Tatzber, F. (1992). Inhibition of LDL oxidation by antioxidants. In: Emerit, I., Chance, B. (eds) Free Radicals and Aging. EXS, vol 62. Birkhäuser Basel. https://doi.org/10.1007/978-3-0348-7460-1_15

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  • DOI: https://doi.org/10.1007/978-3-0348-7460-1_15

  • Publisher Name: Birkhäuser Basel

  • Print ISBN: 978-3-0348-7462-5

  • Online ISBN: 978-3-0348-7460-1

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