Clinical Reviews in Allergy & Immunology

, Volume 18, Issue 1, pp 73–86 | Cite as

Autoimmunity in atherosclerosis

The role of autoantigens
  • Jacob George
  • Dror Harats
  • Yehuda Shoenfeld
Article

Keywords

Clinical Review Immunology Volume apoE Deficient Mouse apoE Mouse Fatty Streak Formation 

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References

  1. 1.
    Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 1993; 362:801–809.PubMedCrossRefGoogle Scholar
  2. 2.
    Ross R Atherosclerosis: an inflammatory condition. N Eng J Med 1999; 340:115–126.CrossRefGoogle Scholar
  3. 3.
    Capron L. Chlamydia in coronary plaques: hidden culprits or harmless hobo? Nature Med 1996; 8:856–857.Google Scholar
  4. 4.
    Cook PJ, Lip GYH. Infectious agents and atherosclerotic vascular disease. Q J Med 1996; 89:727–735.Google Scholar
  5. 5.
    Libby P, Egan D, Scarlatos S. Roles of infectious agents in atherosclerosis and restenosis. An assessment of the evidence and need for future research. Circulation 1997; 96:4095–4103.PubMedGoogle Scholar
  6. 6.
    Plump AS, Smith JD, Hayek T, Aalto-Setala, K, Walsh A, Verstuyft JG, et al. Severe hypercholesterolemia and atherosclerosis in apolipoprotein-E deficient mice created by homologous recombination in ES cells. Cell 1992; 71:343–353.PubMedCrossRefGoogle Scholar
  7. 7.
    Zhang SH, Reddick RL, Piedrahita, JA, Maeda N. Spontaneous hypercholes-terolemia and arterial lesions in mice lacking apolipoprotein E. Science 1992; 258:468–471.PubMedCrossRefGoogle Scholar
  8. 8.
    Ishibashi S, Brown MS, Goldstein JL, Gerard RD, Hammer RE, Herz J. Hyper-cholesterolemia in LDL receptor knockout mice and its reversal by adenovirus mediated gene delivery. J. Clin Invest 1993; 92:883–893.PubMedGoogle Scholar
  9. 9.
    Palinski W, Ord VA, Plump AS, Breslow JL, Steinberg D, Witztum JL. Apo-Edeficient mice are a model of lipoprotein oxidastion in atherogenesis. Demonstration of oxidation-specific epitopes in lesions and high titers of autoantibodies to malondialdehy de-lysine in serum. Arterioscler Thromb 1994; 14:605–616.PubMedGoogle Scholar
  10. 10.
    Rosellaar SE, Kakkanathu PX, Daugherty A. Lymphocyte populations in athero-sclerotic lesions of apo-E−/− and LDL receptor−/− mice; Decreasing density with disease progression. Arteriolscler Thromb Vasc Biol 1996; 16:1013–1018.Google Scholar
  11. 11.
    Paigen B, Morrow A, Holmes PA, Mitchell D, Williams RA. Quantitative assessment of atherosclerotic lesions in mice. Atherosclerosis 1987; 68:231–240.PubMedCrossRefGoogle Scholar
  12. 12.
    Libby P, Hansson GK. Involvement of the immune system in human atherogenesis: Current knowledge and unanswered questions. Lab Invest 1991; 64:5–11.PubMedGoogle Scholar
  13. 13.
    Wick G, Schett G, Amberger A, Kleindienst R, Xu Q. Is atherosclerosis an immunologically mediated disease? Immunol Today 1995; 16:27–33.PubMedCrossRefGoogle Scholar
  14. 14.
    George J, Harats D, Gilburd B, Shoenfeld Y. Emerging cross-regulatory roles of immunity and autoimmunity in atherosclerosis. Immunol Res 1996; 155:315–322.Google Scholar
  15. 15.
    Witztum J, Steinberg D. Role of oxidized low density lipoprotein in atherogenesis. J Clin Invest 1991; 88:1785–1792.PubMedGoogle Scholar
  16. 16.
    Palinski W, Rosenfeld ME, YIa-Herttuala S, et al. Low density lipoprotein undergoes oxidative modification in vivo. Proc Natl Acad Sci USA 1989; 86:1372–1376.PubMedCrossRefGoogle Scholar
  17. 17.
    Quinn MT, Parthasarathy S, Steinberg D. Lysophosphatidylcholine: a chemotactic factor for human monocytes and its potential role in atherogenesis. Proc Natl Acad Sci. USA 1988; 85:2805–2809.PubMedCrossRefGoogle Scholar
  18. 18.
    Schafer-Elinder L, Hedin U, Dumitrescu A, Larsson P, Frostegard J, Claesson HE. Presence of different isoforms of phsospholipase A2 in tissue slices from atherosclerotic carotid plaque. Arteriscler Thromb Vasc Biol 1997; 17:2257–2263.Google Scholar
  19. 19.
    Berliner JA, Territo MC, Sevanian A, et al. Minimally modified LDL stimulates monocyte endothelial interactions, J Clin Invest 1990; 85:1260–1266.PubMedGoogle Scholar
  20. 20.
    McMurray HE, Parthasarathy HF, Steinberg D. Oxidatively modified low density lipoprotein is a chemoreactant for human T lymphocytes. J Clin Invest 1993; 92:1004–1008.PubMedGoogle Scholar
  21. 21.
    Cushing SD, Berliner AJ, Valente MC, et al. Minimally modified LDL induces monocyte chemotactic factor 1 in human endothelial and smooth muscle cells. Proc Nantl Acad Sci USA 1990; 87:5134–5138.CrossRefGoogle Scholar
  22. 22.
    Rajavahishisth TB, Andalibi A, Tedrrito MC. Induction of endothelial cell expression of granulocyte and macrophage colony stimulating factors by modified low density lipoproteins. Nature (Lond.) 1990; 344:254–257.CrossRefGoogle Scholar
  23. 23.
    Heery JM, Kozak M, Stafforini DM, et al. Oxidatively modified LDL contains phospholipids with platelet activating factor like activity and stimulates the growth of smooth muscle cells. J Clin Invest 1995; 96:2322–2330.PubMedGoogle Scholar
  24. 24.
    Stemme S, Faber B, Holm J. T lymphocytes from human atherosclerotic plaques recognize oxidized low density lipoprotein. Proc Natl Acad Sci USA 1995; 92:3893–3897.PubMedCrossRefGoogle Scholar
  25. 25.
    Bergmark C, Wu R, De Faire U, et al. Patients with early onset peripheral vascular disease have increased levels of antibodies against oxidized LDL. Arterioscler Throm Vasc Biol 1995; 15:441–445.Google Scholar
  26. 26.
    Salonen JT, Yla-Herttuala S, Yamamoto R, et al. Antibodies against oxidized LDL and the progression of carotid atherosclerosis. Lancet 1992; 339:883–887.PubMedCrossRefGoogle Scholar
  27. 27.
    Puurunen M, Manttari M, Manninen V, et al. Antibody against oxidized LDL predicting myocardial infarction. Arch Intern Med 1994; 154:2605–2609.PubMedCrossRefGoogle Scholar
  28. 28.
    Virella G, Virella I, Leman RB, et al. Anti-oxidized LDL antibodies in patients with coronary heart disease and healthy controls. Int J Clin Lab Res 1993; 23:95–101.PubMedCrossRefGoogle Scholar
  29. 29.
    Klimov AN, Denisenko AD, Popov AV, et al. Lipoprotein-antibody immune complexes; their catabolism and role in foam cell formation. Atherosclerosis 1985; 58:1–15.PubMedCrossRefGoogle Scholar
  30. 30.
    Khoo JC, Miller E, Pio F, et al. Monoclonal antibodies against LDL further enhance macrophage uptake of LDL aggregates. Arterioscler Thromb 1992; 12:1258–1266.PubMedGoogle Scholar
  31. 31.
    Horkko S, Bird DA, Miller E, Itabe H, Leitinger N, Subbanagounder R, et al. Monoclonal autoantibodies specific for oxidized phopholipid-protein adducts inhibit macrophage uptake of oxidized low density lipoprotein. J Clin Inves 1999; 103:117–128.Google Scholar
  32. 32.
    Palinski W, Miller E, Witztum JL. Immunization of low density lipoprotein (LDL) deficient rabbits with homologeous malondiatldehyde-modified LDL reduces atherogenesis. Proc Natl Acad Sci USA 1995; 92:821–825.PubMedCrossRefGoogle Scholar
  33. 33.
    Alving CR, Swartz GM, Wassef NM, et al. Immunization with cholesterol rich liposomes induces anti-cholesterol Antibodies and reduces diet induced hyper-choleste rolemia and plaque formation. J Lab Clin Med 1996; 127:40–49.PubMedCrossRefGoogle Scholar
  34. 34.
    George J, Afek A, Gilburd B, Levkovitz H, Shaish A, Goldberg I, et al. Hyper-immunization of apoE deficient mice with homologous MDA-low density lipoprotein suppresses early atherogenesis. Atherosclerosis 1998; 138:147–152.PubMedCrossRefGoogle Scholar
  35. 35.
    Freigang S, Horkko S, Miller E, Witztum JL, Palinski W. Immunization of LDL receptor deficient mice with homologous malondialdehyde modified and native LDL redcuces atherosclerosis progression by mechanisms other than induction of high titers of antibodies to oxidative neoepitopes. Arteriscler Thromb Vasc Biol 1998; 18:1972–1982.Google Scholar
  36. 36.
    Lindquist S, Craig EA. The heat shock proteins. Annu Rev Genet 1988; 22:631–677.PubMedCrossRefGoogle Scholar
  37. 37.
    Ellis J, Proteins as molecular chaperones. Nature 1987; 328:378, 379.PubMedCrossRefGoogle Scholar
  38. 38.
    Jones DB, Hunter NR, Duff GW. Heat shock protein 65 as a beta cell antigen of insulin dependent diabetes. Lancet 1990; 336:583–585.PubMedCrossRefGoogle Scholar
  39. 39.
    Winfield JB. Stress proteins, arthritis and autoimmunity. Artritis Rheum 1989; 32:1497–1504.CrossRefGoogle Scholar
  40. 40.
    Lai NS, Lan JL, Yu CL, et al. Antibody to mycoba cterium tuberculosis 65 kDa heat shock protein in patients with rheumatoid arthritis: a survey of antigen specific antibody isotypes and subclasses in an endemic area of previous tuber-culosis infection. Ann Rheum Dis 1995; 54:225–228.PubMedCrossRefGoogle Scholar
  41. 41.
    Karopoulos C, Rowley MJ, Handley CJ, et al. Antibody reactivity to mycobacterial 65 kDa heat shock protein: relevance to autoimmunity. J Autoimmunity 1995; 8:235–248.CrossRefGoogle Scholar
  42. 42.
    Xu Q, Dietrich H, Steiner HJ, et al. Induction of arteriosclerosis in normocho-lesterolemic mice rabbits by immunization with heat shock protein 65. Arteriosclerosis Thromb 1992; 12:789–799.Google Scholar
  43. 43.
    Xu Q, Kleindienst W, Waitz H. et al. Increased expression of heat shock protein 65 coincides with a population of infiltrating T lymphocytes in atherosclerotic lesions of rabbits specifically responding to heat shock protein 65. J Clin Invest 1993 91:2693–2702.PubMedGoogle Scholar
  44. 44.
    J. George, A. Afek, B. Gilburd, D. Harats, M. Blank, I. Goldberg, Y. et al. Accellerated fatty streak formation in C57BL/6J mice by immunization with heat shock protein 65. Arteriscler Thromb Vasc Biol. 1999; 19:505–510.Google Scholar
  45. 45.
    Xu Q, Willeit J, Marosi M, et al. Association of serum antibodies to heat shock protein 65 with carotid atherosclerosis. Lancet 1993; 341:255–259.PubMedCrossRefGoogle Scholar
  46. 46.
    Verdegaal EME, Zegveld S, van Furth R. Heat shock 65 induces CD62e, CD106, and CD54 on cultured human endothelial cells and increases their adhesiveness for monocytes and granulocytes. J Immunol 1996; 157:369–376.PubMedGoogle Scholar
  47. 47.
    Valesini G, Shoenfeld Y. A new player in the antiphospholipid syndrome: the \2 glycorprotein cofactor. Autoimmunity 1992; 14:105–110.PubMedGoogle Scholar
  48. 48.
    Kandia DA, Krilis SA. Beta 2-glycorprotein I. Lupus 1994; 3:207–212.Google Scholar
  49. 49.
    Galli M, Comfurius MP, Maassen C, Hemker HC, De-Bates MH, van-Breda-Vriesman PJ, et al. Anticardiolipin antibodies (ACA) directed not to cardiolipin but to a plasma protein cofator. Lancet 1990; 335:1544–1547.PubMedCrossRefGoogle Scholar
  50. 50.
    McNeil HP, Simpson RJ, Chesterman CN, Krilis SA. Antiphospholipid antibodies are directed against a complex antigen that includes a lipid binding inhibitor of coagulation: β2GPI (apolipoprotein H). Proc Natl Acad Sci USA 1990; 87:4120–4124.PubMedCrossRefGoogle Scholar
  51. 51.
    Matsuura E, Igarashi Y, Fujimoto M, Ichikawa D, Suzuki T, Sumida T, et al. Heterogeneity of anticardioloipin antibodies defined by the anticardiolipin cofactor. J Immunol 1992; 148:3885–3891.PubMedGoogle Scholar
  52. 52.
    Hojnik M, Gilburd B, Ziporen L, Blank M, Tomer Y, Scheinberg MA, et al. Anti-cardiolipin antibodies in infections are heterogenous in their dependency in β2 glycoprotein I: analysis of anticardiolipin in leprosy. Lupus 1994; 3:515–520.PubMedGoogle Scholar
  53. 53.
    Louizou S, Cazabon, JK, Walport JM, Tait D, So AK. Similarities of specificity and cofactor dependence in serum antiphospholipid antibodies from patients with human parvovirus B19 infection and from those with systemic lupus erythematosus. Arthritis Rheum 1997; 40:103–109.CrossRefGoogle Scholar
  54. 54.
    Tsutsumi A, Matsuura E, Ichikawa K, Fujisaku A, Mukai M, Kobayashi S, Koike T. Antibodies to β2GPI and clinical manifestations in patients with systemic lupus erythematosus. Arthritis Rheum 1996; 39:1466–1474.PubMedCrossRefGoogle Scholar
  55. 55.
    Simantov R, LaSala JM, Lo SK, Gharavi AE, Samaritano LR, Salmon JE, Silverstein RL. Activation of cultured endothelial cells by antiphopholipid antibodies. J Clin Invest 1995; 96:2211–2219.PubMedGoogle Scholar
  56. 56.
    George J, Blank M, Levy Y, Meroni PL, Damianovich M, Tincani A, Shoenfeld Y. Differential effects of anti-β2GPI antibodies on endothelial cells and on the manifestations of experimental antiphospholipid syndrome. Circulastion 1998; 97:900–906.Google Scholar
  57. 57.
    George J, Blank M, Gilburd B, Hojnik M, Shenkman B., Tamarin I, et al. Immunologic characterization and functional properties of murine antibodies raised against deleted mutants of β2-glycoprotein I. Int Immunol 1997; 9:913.PubMedCrossRefGoogle Scholar
  58. 58.
    Hasunuma Y, Matsuura E, Makita Z, Katahira T, Nishi S, Koike T. Involvement of β2 glycoprotein I and anticardiolipin antibodies in oxidatively modified low density lipoprotein uptake by macrophages. Clin Exp Immunol 1997; 107:569–574.PubMedCrossRefGoogle Scholar
  59. 60.
    George J, Afek A, Gilburd B, Asron-Maor A, Shaish A, Levkovitz H, et al. Induction of early atherosclerosis in LDL receptor deficient mice immunized with beta 2 glycoprotein I. Circulation 1998; 15:1108–1115.Google Scholar
  60. 61.
    Afek A, George J, Shoenfeld Y, Gilburd B, Levy Y, Keren P, Shaish A, Harats D. Enhanced atherosclerosis in apoE deficient mice by immunization with β2-glycoprotein I. Pathobiology 1999; 67:19–25.PubMedCrossRefGoogle Scholar
  61. 62.
    George J, Harats D, Gilburd B, Afek A, Levy Y, Schneiderman, J. et al. Immunolocalization of β--glycoprotein I (apolipoprotein H) to human athero-sclerotic plaques: potential implication for lesion progression. Circulation 1999; 99:2227–2230.PubMedGoogle Scholar
  62. 63.
    George J, Harats D, Gilburd B, Levy Y, Langevitz P, Shoenfeld Y. A therosclerosis related markers in systemic lupus erytheatosus patients: the role of humoral immunity in enhanced atherogenesis. Lupus 1999; 8:220–226.PubMedCrossRefGoogle Scholar
  63. 64.
    George J, Afek A, Gilburd B, Levy Y, Blank M, Kopolovic Y, et al. Athero-sclerosis in LDL receptor knockout mice is accelerated by immunization with anticardiolipin antibodies. Lupus 1997; 6:723–729.PubMedGoogle Scholar

Copyright information

© Humana Press Inc. 2000

Authors and Affiliations

  • Jacob George
    • 1
    • 3
  • Dror Harats
    • 2
    • 4
  • Yehuda Shoenfeld
    • 1
    • 3
  1. 1.Department of MedicineSheba Medical CenterTel-HashomerIsrael
  2. 2.The Institute of Lipid and Atherosclerosis ResearchSheba Medical CenterTel-HashomerIsrael
  3. 3.Research Unit of Auto immune DiseasesSheba Medical CenterTel-HashomerIsrael
  4. 4.Sackler Faculty of MedicineTel-Aviv UniversityTel-AvivIsrael

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