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The Autoantibody Repertoire Against Copper- or Macrophage-Modified LDL Differs in Normolipidemics and Hypercholesterolemic Patients

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Abstract

We have analyzed the antibody repertoire from normo- and hypercholesterolemic subjects to investigate how it can be related to macrophage-dependent modification of low-density lipoproteins, in comparison to the commonly used copper-oxidized LDL. Preexisting natural antibodies in plasma from normo- and hypercholesterolemic individuals were tested for their reactivity against copper ion oxidized LDL and LDL modified by macrophages. A crosswise comparison between these two antigen preparations demonstrated a different antibody repertoire in normo- and hypercholesterolemic patients. This study suggest that the search for antibodies that can influence the progression or regression of an atherosclerotic process has to take into account the process by which LDL is modified, and the repertoire of antibodies that is generated in the normal population, in comparison to that with, or at risk for, coronary artery diseases.

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REFERENCES

  1. Ross R, Glomset JA: The pathogenesis of atherosclerosis. N Eng J Med 295:369-377, 1976

    Google Scholar 

  2. Ross R: Atherosclerosis—An inflammatory disease. N Engl J Med 340:115-126, 1999

    Google Scholar 

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

    Google Scholar 

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

    Google Scholar 

  5. Frostegard J, Haegerstrand A, Gidlund M, Nilsson J: Biologically modified LDL increases the adhesive properties of endothelial cells. Atherosclerosis 90:119-126, 1991

    Google Scholar 

  6. Libby P: Changing concepts of atherogenesis. J Intern Med 247:349-358, 2000

    Google Scholar 

  7. Folcik VA, Aamir R, Cathcart MK: Cytokine modulation of LDL oxidation by activated human monocytes. Arterioscler Thromb Vasc Biol 17:1954-1961, 1997

    Google Scholar 

  8. Jonasson L, Holm J, Skalli O, Bondjers G, and Hansson GK: Regional accumulations of T cells, macrophages, and smooth muscle cells in the human atherosclerotic plaque. Arteriosclerosis 6:131-138, 1986

    Google Scholar 

  9. Ross R: The patogenesis of atherosclerosis: A perspective for the 1990s. Nature 362:801-809, 1993

    Google Scholar 

  10. Stemme S, Faber B, Holm J, Wiklund O, Witztum JL, Hansson GK: T lymphocytes from human atherosclerotic plaques recognize oxidized low density lipoprotein. Proc Natl Acad Sci USA 92:3893-3897, 1995

    Google Scholar 

  11. Zhou X, Hansson GK: Detection of B cells and proinflammatory cytokines in atherosclerotic plaques of hypercholesterolaemic apolipoprotein E knockout mice. Scand J Immunol 50:25-30, 1999

    Google Scholar 

  12. Shoenfeld Y, Sherer Y, George J, Harats D: Autoantibodies associated with atherosclerosis. Ann Med 32(Suppl 1):37-40, 2000

    Google Scholar 

  13. Palinski W, Yla-Herttuala S, Rosenfeld ME, Butler SW, Socher SA, Parthasarathy S, Curtiss LK, Witztum JL: Antisera and monoclonal antibodies specific for epitopes generated during oxidative modification of low density lipoprotein. Arteriosclerosis 10:325-335, 1990

    Google Scholar 

  14. Bui MN, Sack MN, Moutsatsos G, Lu DY, Katz P, McCown R, Breall JA, Rackley CE: Autoantibody titers to oxidized low-density lipoprotein in patients with coronary atherosclerosis. Am Heart J 131:663-667, 1996

    Google Scholar 

  15. Puurunen M, Manttari M, Manninen V, Tenkanen L, Alfthan G, Ehnholm C, Vaarala O, Aho K, Palosuo T: Antibody against oxidized low-density lipoprotein predicting myocardial infarction. Arch Intern Med 154:2605-2609, 1994

    Google Scholar 

  16. Maggi E, Marchesi E, Ravetta V, Martignoni A, Finardi G, Bellomo G: Presence of autoantibodies against oxidatively modified low-density lipoprotein in essential hypertension: A biochemical signature of an enhanced in vivo low-density lipoprotein oxidation. J Hypertens 13:129-138, 1995

    Google Scholar 

  17. Bergmark C, Wu R, de Faire U, Lefvert AK, Swedenborg J: Patients with early-onset peripheral vascular disease have increased levels of autoantibodies against oxidized LDL. Arterioscler Thromb Vasc Biol 15:441-445, 1995

    Google Scholar 

  18. Zaratin A, Gidlund M, Boschcov P, Castilho L, Cotta de Faria E: Antibodies against oxidized low-density lipoprotein in normolipidemic smokers. Am J Cardiol 90:651, 2002

    Google Scholar 

  19. Shoji T, Nishizawa Y, Fukumoto M, Shimamura K, Kimura J, Kanda H, Emoto M, Kawagishi T, Morii H: Inverse relationship between circulating oxidized low density lipoprotein (oxLDL) and anti-oxLDL antibody levels in healthy subjects. Atherosclerosis 148:171-177, 2000

    Google Scholar 

  20. Uusitupa MI, Niskanen L, Luoma J, Vilja P, Mercuri M, Rauramaa R, Yla-Herttuala S: Autoantibodies against oxidized LDL do not predict atherosclerotic vascular disease in non-insulin-dependent diabetes mellitus. Arterioscler Thromb Vasc Biol 16:1236-1242, 1996

    Google Scholar 

  21. Hulthe J, Wikstrand J, Lidell A, Wendelhag I, Hansson GK, Wiklund O: Antibody titers against oxidized LDL are not elevated in patients with familial hypercholesterolemia. Arterioscler Thromb Vasc Biol 18:1203-1211, 1998

    Google Scholar 

  22. van de Vijver LP, Steyger R, van Poppel G, Boer JM, Kruijssen DA, Seidell JC, Princen HM: Autoantibodies against MDA-LDL in subjects with severe and minor atherosclerosis and healthy population controls. Atherosclerosis 122:245-253, 1996

    Google Scholar 

  23. Sherer Y, Shoenfeld Y: Immunomodulation for treatment and prevention of atherosclerosis. Autoimmunity Rev 1:21-27, 2002

    Google Scholar 

  24. Damasceno NR, Goto H, Rodrigues FM, Dias CT, Okawabata FS, Abdalla DS, Gidlund M: Soy protein isolate reduces the oxidizability of LDL and the generation of oxidized LDL autoantibodies in rabbits with diet-induced atherosclerosis. J Nutr 130:2641-2647, 2000

    Google Scholar 

  25. Uint L, Gebara OCE, Pinto LB, Boschcov P, Luz PL, Gildund M: Hormone replacement therapy (HRT) increases antibodies against heat shock protein 65 (Hsp 65) and oxidized LDL (oxLDL). Brazil J Med Biolog Res 36:491-494, 2003

    Google Scholar 

  26. Havel RJ, Eeder HA, Gragdon JH: [The distribution and chemical composition of ultracentrifugally separated lipoproteins in human serum]. J Clin Invest 34:345-353, 1955

    Google Scholar 

  27. Lowry OH, Rosebbough NJ, Farr AL, Randall RJ: Protein measurement with the folin phenol reagent. J Biol Chem. 193:265-275, 1951

    Google Scholar 

  28. Svensjo E, Boschcov P, Ketelhuth DFJ, Jancar S, Gidlund M: Increased microvascular permeability in the hamster cheek pouch induced by oxidized low density lipoprotein (oxLDL) and some fragmented apolipoprotein B proteins. Inflamm Res 52:215-220, 2003

    Google Scholar 

  29. Puhl H, Waeg G, Esterbauer H: Methods to determine oxidation of low-density lipoproteins. Methods Enzymol 233:425-441, 1994

    Google Scholar 

  30. Carvalho MD, Harada LM, Gidlund M, Ketelhuth DF, Boschcov P, Quintao EC: Macrophages take up triacylglycerol-rich emulsions at a faster rate upon co-incubation with native and modified LDL: An investigation on the role of natural chylomicrons in atherosclerosis. J Cell Biochem 84:309-323, 2002

    Google Scholar 

  31. Ketelhuth DFJBP, Carvalho MDT, Gidlund M: Separation of low-density lipoprotein (LDL) and oxidised LDL (oxLDL) subspecies and reactivity against autoantibodies. Revista da Sociedade Brasileira de Medicina Tropical 34, 2001 (Abstract)

  32. Brown MS, Goldstein JL: Lipoprotein metabolism in the macrophage: Implications for cholesterol deposition in atherosclerosis. Annu Rev Biochem 52:223-261, 1983

    Google Scholar 

  33. Hamilton TA, Major JA, Armstrong D, Tebo JM: Oxidized LDL modulates activation of NFkappaB in mononuclear phagocytes by altering the degradation if IkappaBs. J Leukoc Biol 64:667-674, 1998

    Google Scholar 

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Authors and Affiliations

  1. Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil

    Eva C. Fernvik, Daniel F. J. Ketelhuth, Momtchilo Russo & Magnus Gidlund

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  1. Eva C. Fernvik
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  2. Daniel F. J. Ketelhuth
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  3. Momtchilo Russo
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  4. Magnus Gidlund
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Correspondence to Magnus Gidlund.

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Fernvik, E.C., Ketelhuth, D.F.J., Russo, M. et al. The Autoantibody Repertoire Against Copper- or Macrophage-Modified LDL Differs in Normolipidemics and Hypercholesterolemic Patients. J Clin Immunol 24, 170–176 (2004). https://doi.org/10.1023/B:JOCI.0000019782.67993.0b

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  • DOI: https://doi.org/10.1023/B:JOCI.0000019782.67993.0b

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