Skip to main content
Log in

Factors affecting resistance of low density lipoproteins to oxidation

  • Antioxidant Status and Peroxidation
  • Published:


Oxidation resistance (OR) of low density lipoproteins (LDL) is frequently determined by the conjugated diene (CD) assay, in which isolated LDL is exposed to Cu2+ as prooxidant in the range of 1–10 μM. A brief review on major findings obtained with this assay will be given. A consistent observation is that vitamin E supplements or oleic acid-rich diets increase OR. Oxidation indices measured by the CD assay and effects of antioxidants very significantly depend on the Cu2+ concentration used for LDL oxidation. For medium and high Cu2+ concentrations, the relationship between lag time and propagation rate can be described by a simple hyperbolic saturation function, which has the same mathematical form as the Michaelis-Menten equation. At medium and high Cu2+ concentrations (0.5 to 5 μM), vitamin E increases lag time in a dose-dependent manner. The increase is higher for 0.5 μM Cu2+ as compared to 5 μM. At low Cu2+ concentrations (0.5 μM or less), the mechanism of LDL oxidation changes. Significant oxidation occurs in a preoxidation phase, which commences shortly after addition of Cu2+. Preoxidation is not inhibited by vitamin E. It is concluded that much additional work is needed to validate the importance of oxidation indices derived from CD and similar assays.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others



conjugated diene


low density lipoprotein


oxidation resistance


  1. Steinberg, D., Parthasarathy, S., Carew, T.E., Khoo, J.C., and Witztum J.L. (1989) Beyond Cholesterol. Modifications of Low-Density Lipoprotein that Increase Its Atherogenicity,N. Engl J. Med. 320, 915–924.

    Article  PubMed  CAS  Google Scholar 

  2. Esterbauer, H., Gebicki, J., Puhl, H., and Jürgens, G. (1992) The Role of Lipid Peroxidation and Antioxidants in Oxidative Modification of LDL,Free Rad. Biol. Med. 13, 341–390.

    Article  PubMed  CAS  Google Scholar 

  3. Halliwell, B. (1995) Oxidation of Low-Density Lipoproteins: Questions of Initiation, Propagation, and the Effect of Antioxidants,Am. J. Clin. Nutr. 61, 670S-677S.

    PubMed  CAS  Google Scholar 

  4. Esterbauer, H., Striegl, G., Puhl, H., and Rotheneder, M. (1989) Continuous Monitoring ofin Vitro Oxidation of Human Low Density Lipoprotein,Free Rad. Res. Comm. 6, 67–75.

    CAS  Google Scholar 

  5. Regnström, J., Nilsson, J., Tornvall, P., Landau, C., and Hamsten, A. (1992) Susceptibility to Low-Density Lipoprotein Oxidation and Coronary Atherosclerosis in Man,Lancet 339, 1183–1186.

    Article  PubMed  Google Scholar 

  6. Stalenhoef, A.F.H., Defesche, J.C., Kleinveld, H.A., Demacker, P.N.M., and Kastelein, J.J.P. (1994) Decreased Resistance Againstin Vitro Oxidation of LDL from Patients with Familial Defective Apolipoprotein β-100,Arterioscler. Thromb. 14, 489–493.

    PubMed  CAS  Google Scholar 

  7. Kontush, A., Hübner, C., Finckh, B., Kohlschütter, A., and Beisiegel, U. (1994) Low Density Lipoprotein Oxidizability by Copper Correlates to Its Initial Ubiquinol-10 and Polyunsaturated Fatty Acid Content,FEBS Lett. 341, 69–73.

    Article  PubMed  CAS  Google Scholar 

  8. Reaven, P.D., Grasse, B.J., and Tribble, D.L. (1994) Effects of Linoleate-Enriched and Oleate-Enriched Diets in Combination with α-Tocopherol on the Susceptibility of LDL and LDL Subfractions to Oxidative Modification in Humans,Arterioscler. Thromb. 14, 557–566

    PubMed  CAS  Google Scholar 

  9. Sasahara, M., Raines, E.W., Chait, A., Carew, T.E., Steinberg, D., Wahl, P.W., and 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  CAS  Google Scholar 

  10. Nenseter, M.S., Gudmundsen, O., Malterud, K.E., Berg, T., and Drevon, C.A. (1994) Effect of Cholesterol Feeding on the Susceptibility of Lipoproteins to Oxidative Stress,Biochim. Biophys. Acta 1213, 207–214.

    PubMed  CAS  Google Scholar 

  11. Fruebis, J., Steinberg, D., Dresel, H.A., and Carew, T.E. (1994) A Comparison of the Antiatherogenic Effects of Probucol and of a Structural Analogue of Probucol in Low Density Lipoprotein Receptor-Deficient Rabbits,J. Clin. Invest. 94, 392–398.

    PubMed  CAS  Google Scholar 

  12. Thomas, M.J., Thornburg, T., Manning, J., Hooper, K., and Rudel, L.L. (1994) Fatty Acid Composition of Low-Density Lipoprotein Influences Its Susceptibility to Autoxidation,Biochemistry 33, 1828–1834.

    Article  PubMed  CAS  Google Scholar 

  13. Kleinveld, H.A., Demacker, P.N.M., Stalenhoef, A.F.H. (1994) Comparative Study on the Effect of Low-Dose Vitamin E and Probucol on the Susceptibility of LDL to Oxidation and the Progression of Atherosclerosis in Watanabe Heritable Hyperlipidemic Rabbits,Arterioscler. Thromb. 14, 1386–1391.

    PubMed  CAS  Google Scholar 

  14. Maggi, E., Bellazzi, R., Falaschi, F., Frattoni, A., Perani, G., Finardi, G., Gazo, A., Nai, M., Romanini, D., and Bellomo, G. (1994) Enhanced LDL Oxidation in Uremic Patients: An Additional Mechanism for Accelerated Atherosclerosis?Kidney Int. 45, 876–883.

    PubMed  CAS  Google Scholar 

  15. Tribble, D.L., van der Berg, J.J., Motchnik, P.A., Ames, B.N., Lewis D.M., Chait, A., and Krauss, R.M. (1994) Oxidative Susceptibility of Low Density Lipoprotein Subfractions is Related to Their Ubiquinol-10 and α-Tocopherol Content,Proc. Natl. Acad. Sci. USA 91, 1183–1187

    Article  PubMed  CAS  Google Scholar 

  16. Tsai, E.C., Hirsch, I.B., Brunzell, I.D., and Chait A. (1994) Reduced Plasma Peroxyl Radical Trapping Capacity and Increased Susceptibility of LDL to Oxidation in Poorly Controlled IDDM,Diabetes 43, 1010–1014.

    Article  PubMed  CAS  Google Scholar 

  17. Nyyssonen, K., Porkkala, E., Salonen, R., Korpela, H., and Salonen, J.T. (1994) Increase in Oxidation Resistance of Atherogenic Serum Lipoproteins Following Antioxidant Supplementation: A Randomized Double-Blind,Eur. J. Clin. Nutr. 48, 633–642.

    PubMed  CAS  Google Scholar 

  18. Winklhofer-Roob, B.M., Puhl, H., Khoschsorur, G., van't Hof, M.A., Esterbauer, H., and Shmerling, D.H. (1995) Enhanced Resistance to Oxidation of Low Density Lipoproteins and Decreased Lipid Peroxide Formation During β-Carotene Supplementation in Cystic Fibrosis,Free Rad. Biol. Med. 18, 849–859

    Article  PubMed  CAS  Google Scholar 

  19. Jialal, I., Fuller, C.J., and Huet, B.A. (1995) The Effect of α-Tocopherol Supplementation on LDL Oxidation: A Dose-Response Study, Arterioscler. Thromb. Vasc. Biol. 15, 190–198.

    PubMed  CAS  Google Scholar 

  20. Suzukawa, M., Ishikawa, T., Yoshida, H., and Nakamura, H. (1995) Effect ofin vivo Supplementation with Low-Dose Vitamin E on Susceptibility of Low-Density Lipoprotein and High Density Lipoprotein to Oxidative Modification.J. Am. Coll. Nutr. 14, 46–52.

    PubMed  CAS  Google Scholar 

  21. Livrea, M.A., Tesoriere, L., Bongiorno, A., Pintaudi, A.M., Ciaccio, M., and Riccio A. (1995) Contribution of Vitamin A to the Oxidation Resistance of Human Low Density Lipoproteins,Free Rad. Biol. Med. 18, 401–409.

    Article  PubMed  CAS  Google Scholar 

  22. Croft, K.D., Williams, P., Dimmitt, S., Abu-Amsha, R., and Beilin, L.J. (1995) Oxidation of Low Density Lipoproteins: Effect of Antioxidant Content, Fatty Acid Composition and Intrinsic Phospholipase Activity on Susceptibility to Metal Ion-Induced Oxidation,Biochim. Biophys. Acta 1254, 250–256.

    PubMed  Google Scholar 

  23. Gaziano, J.M., Hatta, A., Flynn, M., Johnson, E.J., Krinsky, N.I., Ridler, P.M., Hennekens, C.H., and Frei, B. (1995) Supplementation with β-Carotenein vivo andin vitro Does Not Inhibit Low Density Lipoprotein Oxidation,Atherosclerosis 112, 187–195.

    Article  PubMed  CAS  Google Scholar 

  24. Mosinger, B.J. (1995) Copper-Induced and Photosensitive Oxidation of Serum Low-Density Lipoprotein: The Relation to Cholesterol Level and Inter-Species Differences,Biochim. Biophys. Acta 1270, 73–80.

    PubMed  Google Scholar 

  25. Ramos, P., Gieseg, S.P., Schuster, B., and Esterbauer, H. (1995) Effect of Temperature and Phase Transition on Oxidation Resistance of Low-Density Lipoprotein,J. Lipid Res. 35, 2113–2128.

    Google Scholar 

  26. Gieseg, S.P., and Esterbauer, H. (1994) Low Density Lipoprotein is Saturable by Pro-oxidant Copper,FEBS Lett. 343, 188–194.

    Article  PubMed  CAS  Google Scholar 

  27. Puhl, H., Waeg, G., and Esterbauer, H. (1994) Methods to Determine Oxidation of Low-Density LipoproteinsMethods Enzymol. 233, 425–441.

    Article  PubMed  CAS  Google Scholar 

  28. Esterbauer, H., Dieber-Rotheneder, M., Striegl, G., and Waeg, G. (1991) Role of Vitamin E in Preventing the Oxidation of Low Density Lipoprotein,Am. J. Clin. Nutr. 53, 314S-321S.

    PubMed  CAS  Google Scholar 

  29. Esterbauer, H., Puhl, H., Waeg, G., Krebs, A., and Dieber-Rotheneder, M. (1992) The Role of Vitamin E in Lipoprotein Oxidation, inVitamin E in Health and Disease (Packer, L., and Fuchs, J., eds.) Marcel Dekker, Inc., New York, pp. 649–671.

    Google Scholar 

  30. Bowry, V.W., and Stocker, R. (1993) The Pro-Oxidant Effect of Vitamin E on the Radical-Initiated Oxidation of Human Low-Density Lipoprotein,J. Am. Chem. Soc. 115, 6029–6043.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations


About this article

Cite this article

Ziouzenkova, O., Gieseg, S.P., Ramos, P. et al. Factors affecting resistance of low density lipoproteins to oxidation. Lipids 31, S71–S76 (1996).

Download citation

  • Issue Date:

  • DOI: