Skip to main content
SpringerLink
Log in

Vaccination Against Atherosclerosis

  • Chapter
  • First Online:
Inflammation and Atherosclerosis

  • 1932 Accesses

Abstract

The development of a vaccine to prevent the build-up of atherosclerotic plaques would drastically change the life for millions of individuals and hopefully strongly reduce the number of fatal and nonfatal cardiovascular events. At present, there are several treatments for the disease (e.g. statins, acetylsalicylic acid, and ADP-receptor antagonists) and much can be accomplished through lifestyle changes such as giving up smoking or switching to a low-fat low-cholesterol diet. A large number of prospective, randomized, controlled clinical trials have demonstrated both angiographic and clinical benefits of lipid-lowering therapy. Overall, a significant and clinically worthwhile relative risk reduction ranging from 20% to 40% in major cardiovascular events has been achieved with these strategies, without significant adverse effects or increased noncardiovascular mortality. However, around 60–70% of adverse cardiovascular events continue to occur despite oxidized low-density lipoprotein (oxLDL)-lowering therapies, indicating an obvious need for new therapeutic interventions.

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 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
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

  1. Glass CK, Witztum JL (2001) Atherosclerosis. The road ahead. Cell 104(4):503–516

    PubMed  CAS  Google Scholar 

  2. Palinski W, Witztum JL (2000) Immune responses to oxidative neoepitopes on LDL and phospholipids modulate the development of atherosclerosis. J Intern Med 247(3):371–380

    PubMed  CAS  Google Scholar 

  3. Calara F, Dimayuga P, Niemann A, Thyberg J, Diczfalusy U, Witztum JL et al (1998) An animal model to study local oxidation of LDL and its biological effects in the arterial wall. Arterioscler Thromb Vasc Biol 18(6):884–893

    PubMed  CAS  Google Scholar 

  4. Stemme S, Faber B, Holm J, Wiklund O, Witztum JL, Hansson GK (1995) T lymphocytes from human atherosclerotic plaques recognize oxidized low density lipoprotein. Proc Natl Acad Sci USA 92(9):3893–3897

    PubMed  CAS  Google Scholar 

  5. Regnstrom J, Nilsson J (1994) Lipid oxidation and inflammation-induced intimal fibrosis in coronary heart disease. J Lab Clin Med 124(2):162–168

    PubMed  CAS  Google Scholar 

  6. De Palma R, Del Galdo F, Abbate G, Chiariello M, Calabro R, Forte L et al (2006) Patients with acute coronary syndrome show oligoclonal T-cell recruitment within unstable plaque: evidence for a local, intracoronary immunologic mechanism. Circulation 113(5):640–646

    PubMed  Google Scholar 

  7. Paulsson G, Zhou X, Tornquist E, Hansson GK (2000) Oligoclonal T cell expansions in atherosclerotic lesions of apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol 20(1):10–17

    PubMed  CAS  Google Scholar 

  8. Gordon S (2002) Pattern recognition receptors: doubling up for the innate immune response. Cell 111(7):927–930

    PubMed  CAS  Google Scholar 

  9. Binder CJ, Chang MK, Shaw PX, Miller YI, Hartvigsen K, Dewan A et al (2002) Innate and acquired immunity in atherogenesis. Nat Med 8(11):1218–1226

    PubMed  CAS  Google Scholar 

  10. Shoenfeld Y, Wu R, Dearing LD, Matsuura E (2004) Are anti-oxidized low-density lipoprotein antibodies pathogenic or protective? Circulation 110(17):2552–2558

    PubMed  Google Scholar 

  11. Ameli S, Hultgardh-Nilsson A, Regnstrom J, Calara F, Yano J, Cercek B et al (1996) Effect of immunization with homologous LDL and oxidized LDL on early atherosclerosis in hypercholesterolemic rabbits. Arterioscler Thromb Vasc Biol 16(8):1074–1079

    PubMed  CAS  Google Scholar 

  12. Palinski W, Miller E, Witztum JL (1995) Immunization of low density lipoprotein (LDL) receptor-deficient rabbits with homologous malondialdehyde-modified LDL reduces atherogenesis. Proc Natl Acad Sci USA 92(3):821–825

    PubMed  CAS  Google Scholar 

  13. Fredrikson GN, Soderberg I, Lindholm M, Dimayuga P, Chyu KY, Shah PK et al (2003) Inhibition of atherosclerosis in apoE-null mice by immunization with apoB-100 peptide sequences. Arterioscler Thromb Vasc Biol 23(5):879–884

    PubMed  CAS  Google Scholar 

  14. Freigang S, Horkko S, Miller E, Witztum JL, Palinski W (1998) Immunization of LDL receptor-deficient mice with homologous malondialdehyde-modified and native LDL reduces progression of atherosclerosis by mechanisms other than induction of high titers of antibodies to oxidative neoepitopes. Arterioscler Thromb Vasc Biol 18(12):1972–1982

    PubMed  CAS  Google Scholar 

  15. Nilsson J, Calara F, Regnstrom J, Hultgardh-Nilsson A, Ameli S, Cercek B et al (1997) Immunization with homologous oxidized low density lipoprotein reduces neointimal formation after balloon injury in hypercholesterolemic rabbits. J Am Coll Cardiol 30(7):1886–1891

    PubMed  CAS  Google Scholar 

  16. Maggi E, Chiesa R, Melissano G, Castellano R, Astore D, Grossi A et al (1994) LDL oxidation in patients with severe carotid atherosclerosis. A study of in vitro and in vivo oxidation markers. Arterioscler Thromb 14(12):1892–1899

    PubMed  CAS  Google Scholar 

  17. Palinski W, Ord VA, Plump AS, Breslow JL, Steinberg D, Witztum JL (1994) ApoE-deficient mice are a model of lipoprotein oxidation in atherogenesis. Demonstration of oxidation-specific epitopes in lesions and high titers of autoantibodies to malondialdehyde-lysine in serum. Arterioscler Thromb 14(4):605–616

    PubMed  CAS  Google Scholar 

  18. Palinski W, Rosenfeld ME, Yla-Herttuala S, Gurtner GC, Socher SS, Butler SW et al (1989) Low density lipoprotein undergoes oxidative modification in vivo. Proc Natl Acad Sci USA 86(4):1372–1376

    PubMed  CAS  Google Scholar 

  19. Salonen JT, Yla-Herttuala S, Yamamoto R, Butler S, Korpela H, Salonen R et al (1992) Autoantibody against oxidised LDL and progression of carotid atherosclerosis. Lancet 339(8798):883–887

    PubMed  CAS  Google Scholar 

  20. Yla-Herttuala S, Palinski W, Butler SW, Picard S, Steinberg D, Witztum JL (1994) Rabbit and human atherosclerotic lesions contain IgG that recognizes epitopes of oxidized LDL. Arterioscler Thromb 14(1):32–40

    PubMed  CAS  Google Scholar 

  21. Zhou X, Paulsson G, Stemme S, Hansson GK (1998) Hypercholesterolemia is associated with a T helper (Th) 1/Th2 switch of the autoimmune response in atherosclerotic apoE-knockout mice. J Clin Invest 101(8):1717–1725

    PubMed  CAS  Google Scholar 

  22. Faviou E, Vourli G, Nounopoulos C, Zachari A, Dionyssiou-Asteriou A (2005) Circulating oxidized low density lipoprotein, autoantibodies against them and homocysteine serum levels in diagnosis and estimation of severity of coronary artery disease. Free Radical Res 39(4):419–429

    CAS  Google Scholar 

  23. Soltesz P, Veres K, Laczik R, Der H, Csipo I, Timar O et al (2007) Evaluation of antibodies to oxidized low-density lipoprotein and assessment of C-reactive protein in acute coronary syndrome and stable coronary artery disease. Thromb Haemost 98(2):413–419

    PubMed  CAS  Google Scholar 

  24. Tsai WC, Li YH, Chao TH, Chen JH (2002) Relation between antibody against oxidized low-density lipoprotein and extent of coronary atherosclerosis. J Formos Med Assoc 101(10):681–684

    PubMed  CAS  Google Scholar 

  25. Smook ML, van Leeuwen M, Heeringa P, Damoiseaux JG, Theunissen R, Daemen MJ et al (2008) Anti-oxLDL antibody isotype levels, as potential markers for progressive atherosclerosis in APOE and APOECD40L mice. Clin Exp Immunol 154(2):264–269

    PubMed  CAS  Google Scholar 

  26. Tornvall P, Waeg G, Nilsson J, Hamsten A, Regnstrom J (2003) Autoantibodies against modified low-density lipoproteins in coronary artery disease. Atherosclerosis 167(2):347–353

    PubMed  CAS  Google Scholar 

  27. Steinberg D, Lewis A (1997) Conner memorial lecture. Oxidative modification of LDL and atherogenesis. Circulation 95(4):1062–1071

    PubMed  CAS  Google Scholar 

  28. Yla-Herttuala S, Palinski W, Rosenfeld ME, Parthasarathy S, Carew TE, Butler S et al (1989) Evidence for the presence of oxidatively modified low density lipoprotein in atherosclerotic lesions of rabbit and man. J Clin Invest 84(4):1086–1095

    PubMed  CAS  Google Scholar 

  29. Ehara S, Ueda M, Naruko T, Haze K, Itoh A, Otsuka M et al (2001) Elevated levels of oxidized low density lipoprotein show a positive relationship with the severity of acute coronary syndromes. Circulation 103(15):1955–1960

    PubMed  CAS  Google Scholar 

  30. Holvoet P, Vanhaecke J, Janssens S, Van de Werf F, Collen D (1998) Oxidized LDL and malondialdehyde-modified LDL in patients with acute coronary syndromes and stable coronary artery disease. Circulation 98(15):1487–1494

    PubMed  CAS  Google Scholar 

  31. Krych-Goldberg M, Atkinson JP (2001) Structure-function relationships of complement receptor type 1. Immunol Rev 180:112–122

    PubMed  CAS  Google Scholar 

  32. Fredrikson GN, Hedblad B, Berglund G, Alm R, Ares M, Cercek B et al (2003) Identification of immune responses against aldehyde-modified peptide sequences in apoB associated with cardiovascular disease. Arterioscler Thromb Vasc Biol 23(5):872–878

    PubMed  CAS  Google Scholar 

  33. Nicoletti A, Paulsson G, Caligiuri G, Zhou X, Hansson GK (2000) Induction of neonatal tolerance to oxidized lipoprotein reduces atherosclerosis in ApoE knockout mice. Mol Med 6(4):283–290

    PubMed  CAS  Google Scholar 

  34. Chyu KY, Reyes OS, Zhao X, Yano J, Dimayuga P, Nilsson J et al (2004) Timing affects the efficacy of LDL immunization on atherosclerotic lesions in apoE(−/−) mice. Atherosclerosis 176(1):27–35

    PubMed  CAS  Google Scholar 

  35. Zhou X, Caligiuri G, Hamsten A, Lefvert AK, Hansson GK (2001) LDL immunization induces T-cell-dependent antibody formation and protection against atherosclerosis. Arterioscler Thromb Vasc Biol 21(1):108–114

    PubMed  CAS  Google Scholar 

  36. Fredrikson GN, Andersson L, Soderberg I, Dimayuga P, Chyu KY, Shah PK et al (2005) Atheroprotective immunization with MDA-modified apoB-100 peptide sequences is associated with activation of Th2 specific antibody expression. Autoimmunity 38(2):171–179

    PubMed  CAS  Google Scholar 

  37. Habets KL, van Puijvelde GH, van Duivenvoorde LM, van Wanrooij EJ, de Vos P, Tervaert JW et al (2010) Vaccination using oxidized low-density lipoprotein-pulsed dendritic cells reduces atherosclerosis in LDL receptor-deficient mice. Cardiovasc Res 85(3):622–630

    PubMed  CAS  Google Scholar 

  38. Hjerpe C, Johansson D, Hermansson A, Hansson GK, Zhou X (2010) Dendritic cells pulsed with malondialdehyde modified low density lipoprotein aggravate atherosclerosis in apoE(−/−) mice. Atherosclerosis 209(2):436–441

    PubMed  CAS  Google Scholar 

  39. Elhage R, Jawien J, Rudling M, Ljunggren HG, Takeda K, Akira S et al (2003) Reduced atherosclerosis in interleukin-18 deficient apolipoprotein E-knockout mice. Cardiovasc Res 59(1):234–240

    PubMed  CAS  Google Scholar 

  40. Hauer AD, Uyttenhove C, de Vos P, Stroobant V, Renauld JC, van Berkel TJ et al (2005) Blockade of interleukin-12 function by protein vaccination attenuates atherosclerosis. Circulation 112(7):1054–1062

    PubMed  CAS  Google Scholar 

  41. Whitman SC, Ravisankar P, Daugherty A (2002) IFN-gamma deficiency exerts gender-specific effects on atherogenesis in apolipoprotein E−/− mice. J Interferon Cytokine Res 22(6):661–670

    PubMed  CAS  Google Scholar 

  42. Pinderski LJ, Fischbein MP, Subbanagounder G, Fishbein MC, Kubo N, Cheroutre H et al (2002) Overexpression of interleukin-10 by activated T lymphocytes inhibits atherosclerosis in LDL receptor-deficient Mice by altering lymphocyte and macrophage phenotypes. Circ Res 90(10):1064–1071

    PubMed  CAS  Google Scholar 

  43. Von Der Thusen JH, Kuiper J, Fekkes ML, De Vos P, Van Berkel TJ, Biessen EA (2001) Attenuation of atherogenesis by systemic and local adenovirus-mediated gene transfer of interleukin-10 in LDLr−/− mice. FASEB J 15(14):2730–2732

    Google Scholar 

  44. Davenport P, Tipping PG (2003) The role of interleukin-4 and interleukin-12 in the progression of atherosclerosis in apolipoprotein E-deficient mice. Am J Pathol 163(3):1117–1125

    PubMed  CAS  Google Scholar 

  45. Ait-Oufella H, Salomon BL, Potteaux S, Robertson AK, Gourdy P, Zoll J et al (2006) Natural regulatory T cells control the development of atherosclerosis in mice. Nat Med 12(2):178–180

    PubMed  CAS  Google Scholar 

  46. Mallat Z, Ait-Oufella H, Tedgui A (2005) Regulatory T cell responses: potential role in the control of atherosclerosis. Curr Opin Lipidol 16(5):518–524

    PubMed  CAS  Google Scholar 

  47. Shi FD, Li H, Wang H, Bai X, van der Meide PH, Link H et al (1999) Mechanisms of nasal tolerance induction in experimental autoimmune myasthenia gravis: identification of regulatory cells. J Immunol 162(10):5757–5763

    PubMed  CAS  Google Scholar 

  48. van Puijvelde GH, Hauer AD, de Vos P, van den Heuvel R, van Herwijnen MJ, van der Zee R et al (2006) Induction of oral tolerance to oxidized low-density lipoprotein ameliorates atherosclerosis. Circulation 114(18):1968–1976

    PubMed  Google Scholar 

  49. Fredrikson GN, Berglund G, Alm R, Nilsson JA, Shah PK, Nilsson J (2006) Identification of autoantibodies in human plasma recognizing an apoB-100 LDL receptor binding site peptide. J Lipid Res 47(9):2049–2054

    PubMed  CAS  Google Scholar 

  50. Chyu KY, Zhao X, Reyes OS, Babbidge SM, Dimayuga PC, Yano J et al (2005) Immunization using an apoB-100 related epitope reduces atherosclerosis and plaque inflammation in hypercholesterolemic apoE(−/−) mice. Biochem Biophys Res Commun 338(4):1982–1989

    PubMed  CAS  Google Scholar 

  51. Fredrikson GN, Bjorkbacka H, Soderberg I, Ljungcrantz I, Nilsson J (2008) Treatment with apoB peptide vaccines inhibits atherosclerosis in human apoB-100 transgenic mice without inducing an increase in peptide-specific antibodies. J Intern Med 264(6):563–570

    PubMed  CAS  Google Scholar 

  52. Fredrikson GN, Hedblad B, Berglund G, Alm R, Nilsson JA, Schiopu A et al (2007) Association between IgM against an aldehyde-modified peptide in apolipoprotein B-100 and progression of carotid disease. Stroke 38(5):1495–1500

    PubMed  CAS  Google Scholar 

  53. Sjogren P, Fredrikson GN, Samnegard A, Ericsson CG, Ohrvik J, Fisher RM et al (2008) High plasma concentrations of autoantibodies against native peptide 210 of apoB-100 are related to less coronary atherosclerosis and lower risk of myocardial infarction. Eur Heart J 29(18):2218–2226

    PubMed  Google Scholar 

  54. Binder CJ, Horkko S, Dewan A, Chang MK, Kieu EP, Goodyear CS et al (2003) Pneumococcal vaccination decreases atherosclerotic lesion formation: molecular mimicry between streptococcus pneumoniae and oxidized LDL. Nat Med 9(6):736–743

    PubMed  CAS  Google Scholar 

  55. Binder CJ, Hartvigsen K, Chang MK, Miller M, Broide D, Palinski W et al (2004) IL-5 links adaptive and natural immunity specific for epitopes of oxidized LDL and protects from atherosclerosis. J Clin Invest 114(3):427–437

    PubMed  CAS  Google Scholar 

  56. Schiopu A, Bengtsson J, Soderberg I, Janciauskiene S, Lindgren S, Ares MP et al (2004) Recombinant human antibodies against aldehyde-modified apolipoprotein B-100 peptide sequences inhibit atherosclerosis. Circulation 110(14):2047–2052

    PubMed  CAS  Google Scholar 

  57. Horkko S, Bird DA, Miller E, Itabe H, Leitinger N, Subbanagounder G et al (1999) Monoclonal autoantibodies specific for oxidized phospholipids or oxidized phospholipid-protein adducts inhibit macrophage uptake of oxidized low-density lipoproteins. J Clin Invest 103(1):117–128

    PubMed  CAS  Google Scholar 

  58. Schiopu A, Frendeus B, Jansson B, Soderberg I, Ljungcrantz I, Araya Z et al (2007) Recombinant antibodies to an oxidized low-density lipoprotein epitope induce rapid regression of atherosclerosis in apobec-1(−/−)/low-density lipoprotein receptor(−/−) mice. J Am Coll Cardiol 50(24):2313–2318

    PubMed  CAS  Google Scholar 

  59. Strom A, Fredrikson GN, Schiopu A, Ljungcrantz I, Soderberg I, Jansson B et al (2007) Inhibition of injury-induced arterial remodelling and carotid atherosclerosis by recombinant human antibodies against aldehyde-modified apoB-100. Atherosclerosis 190(2):298–305

    PubMed  Google Scholar 

  60. Vaarala O, Alfthan G, Jauhiainen M, Leirisalo-Repo M, Aho K, Palosuo T (1993) Crossreaction between antibodies to oxidised low-density lipoprotein and to cardiolipin in systemic lupus erythematosus. Lancet 341(8850):923–925

    PubMed  CAS  Google Scholar 

  61. Kobayashi K, Kishi M, Atsumi T, Bertolaccini ML, Makino H, Sakairi N et al (2003) Circulating oxidized LDL forms complexes with beta2-glycoprotein I: implication as an atherogenic autoantigen. J Lipid Res 44(4):716–726

    PubMed  CAS  Google Scholar 

  62. Lopez D, Garcia-Valladares I, Palafox-Sanchez CA, De La Torre IG, Kobayashi K, Matsuura E et al (2004) Oxidized low-density lipoprotein/beta2-glycoprotein I complexes and autoantibodies to oxLig-1/beta2-glycoprotein I in patients with systemic lupus erythematosus and antiphospholipid syndrome. Am J Clin Pathol 121(3):426–436

    PubMed  CAS  Google Scholar 

  63. Lopez D, Kobayashi K, Merrill JT, Matsuura E, Lopez LR (2003) IgG autoantibodies against beta2-glycoprotein I complexed with a lipid ligand derived from oxidized low-density lipoprotein are associated with arterial thrombosis in antiphospholipid syndrome. Clin Dev Immunol 10(2–4):203–211

    PubMed  CAS  Google Scholar 

  64. Brey RL, Abbott RD, Curb JD, Sharp DS, Ross GW, Stallworth CL et al (2001) Beta(2)-Glycoprotein 1-dependent anticardiolipin antibodies and risk of ischemic stroke and myocardial infarction: the Honolulu heart program. Stroke 32(8):1701–1706

    PubMed  CAS  Google Scholar 

  65. Lopez LR, Dier KJ, Lopez D, Merrill JT, Fink CA (2004) Anti-beta 2-glycoprotein I and antiphosphatidylserine antibodies are predictors of arterial thrombosis in patients with antiphospholipid syndrome. Am J Clin Pathol 121(1):142–149

    PubMed  CAS  Google Scholar 

  66. George J, Harats D, Gilburd B, Afek A, Shaish A, Kopolovic J et al (2000) Adoptive transfer of beta(2)-glycoprotein I-reactive lymphocytes enhances early atherosclerosis in LDL receptor-deficient mice. Circulation 102(15):1822–1827

    PubMed  CAS  Google Scholar 

  67. Afek A, George J, Shoenfeld Y, Gilburd B, Levy Y, Shaish A et al (1999) Enhancement of atherosclerosis in beta-2-glycoprotein I-immunized apolipoprotein E-deficient mice. Pathobiology 67(1):19–25

    PubMed  CAS  Google Scholar 

  68. George J, Yacov N, Breitbart E, Bangio L, Shaish A, Gilburd B et al (2004) Suppression of early atherosclerosis in LDL-receptor deficient mice by oral tolerance with beta 2-glycoprotein I. Cardiovasc Res 62(3):603–609

    PubMed  CAS  Google Scholar 

  69. Chou MY, Hartvigsen K, Hansen LF, Fogelstrand L, Shaw PX, Boullier A et al (2008) Oxidation-specific epitopes are important targets of innate immunity. J Intern Med 263(5):479–488

    PubMed  CAS  Google Scholar 

  70. Shaw PX, Horkko S, Chang MK, Curtiss LK, Palinski W, Silverman GJ et al (2000) Natural antibodies with the T15 idiotype may act in atherosclerosis, apoptotic clearance, and protective immunity. J Clin Invest 105(12):1731–1740

    PubMed  CAS  Google Scholar 

  71. Faria-Neto JR, Chyu KY, Li X, Dimayuga PC, Ferreira C, Yano J et al (2006) Passive immunization with monoclonal IgM antibodies against phosphorylcholine reduces accelerated vein graft atherosclerosis in apolipoprotein E-null mice. Atherosclerosis 189(1):83–90

    PubMed  CAS  Google Scholar 

  72. Caligiuri G, Khallou-Laschet J, Vandaele M, Gaston AT, Delignat S, Mandet C et al (2007) Phosphorylcholine-targeting immunization reduces atherosclerosis. J Am Coll Cardiol 50(6):540–546

    PubMed  CAS  Google Scholar 

  73. Milkman R (1962) Temperature effects on day old drosophila pupae. J Gen Physiol 45:777–799

    PubMed  CAS  Google Scholar 

  74. Young RA, Elliott TJ (1989) Stress proteins, infection, and immune surveillance. Cell 59(1):5–8

    PubMed  CAS  Google Scholar 

  75. Lamb DJ, El-Sankary W, Ferns GA (2003) Molecular mimicry in atherosclerosis: a role for heat shock proteins in immunisation. Atherosclerosis 167(2):177–185

    PubMed  CAS  Google Scholar 

  76. Xu Q, Wick G (1996) The role of heat shock proteins in protection and pathophysiology of the arterial wall. Mol Med Today 2(9):372–379

    PubMed  CAS  Google Scholar 

  77. Amberger A, Maczek C, Jurgens G, Michaelis D, Schett G, Trieb K et al (1997) Co-expression of ICAM-1, VCAM-1, ELAM-1 and Hsp60 in human arterial and venous endothelial cells in response to cytokines and oxidized low-density lipoproteins. Cell Stress Chaperones 2(2):94–103

    PubMed  CAS  Google Scholar 

  78. Wick G, Knoflach M, Xu Q (2004) Autoimmune and inflammatory mechanisms in atherosclerosis. Annu Rev Immunol 22:361–403

    PubMed  CAS  Google Scholar 

  79. Wick G, Schett G, Amberger A, Kleindienst R, Xu Q (1995) Is atherosclerosis an immunologically mediated disease? Immunol Today 16(1):27–33

    PubMed  CAS  Google Scholar 

  80. Kanwar RK, Kanwar JR, Wang D, Ormrod DJ, Krissansen GW (2001) Temporal expression of heat shock proteins 60 and 70 at lesion-prone sites during atherogenesis in ApoE-deficient mice. Arterioscler Thromb Vasc Biol 21(12):1991–1997

    PubMed  CAS  Google Scholar 

  81. Xu Q, Dietrich H, Steiner HJ, Gown AM, Schoel B, Mikuz G et al (1992) Induction of arteriosclerosis in normocholesterolemic rabbits by immunization with heat shock protein 65. Arterioscler Thromb 12(7):789–799

    PubMed  CAS  Google Scholar 

  82. Metzler B, Mayr M, Dietrich H, Singh M, Wiebe E, Xu Q et al (1999) Inhibition of arteriosclerosis by T-cell depletion in normocholesterolemic rabbits immunized with heat shock protein 65. Arterioscler Thromb Vasc Biol 19(8):1905–1911

    PubMed  CAS  Google Scholar 

  83. Xu Q, Kleindienst R, Waitz W, Dietrich H, Wick G (1993) 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 91(6):2693–2702

    PubMed  CAS  Google Scholar 

  84. Benagiano M, D’Elios MM, Amedei A, Azzurri A, van der Zee R, Ciervo A et al (2005) Human 60-kDa heat shock protein is a target autoantigen of T cells derived from atherosclerotic plaques. J Immunol 174(10):6509–6517

    PubMed  CAS  Google Scholar 

  85. Rossmann A, Henderson B, Heidecker B, Seiler R, Fraedrich G, Singh M et al (2008) T-cells from advanced atherosclerotic lesions recognize hHSP60 and have a restricted T-cell receptor repertoire. Exp Gerontol 43(3):229–237

    PubMed  CAS  Google Scholar 

  86. Afek A, George J, Gilburd B, Rauova L, Goldberg I, Kopolovic J et al (2000) Immunization of low-density lipoprotein receptor deficient (LDL-RD) mice with heat shock protein 65 (HSP-65) promotes early atherosclerosis. J Autoimmun 14(2):115–121

    PubMed  CAS  Google Scholar 

  87. George J, Shoenfeld Y, Afek A, Gilburd B, Keren P, Shaish A et al (1999) Enhanced fatty streak formation in C57BL/6 J mice by immunization with heat shock protein-65. Arterioscler Thromb Vasc Biol 19(3):505–510

    PubMed  CAS  Google Scholar 

  88. Mori Y, Kitamura H, Song QH, Kobayashi T, Umemura S, Cyong JC (2000) A new murine model for atherosclerosis with inflammation in the periodontal tissue induced by immunization with heat shock protein 60. Hypertens Res 23(5):475–481

    PubMed  CAS  Google Scholar 

  89. George J, Greenberg S, Barshack I, Goldberg I, Keren G, Roth A (2003) Immunity to heat shock protein 65–an additional determinant in intimal thickening. Atherosclerosis 168(1):33–38

    PubMed  CAS  Google Scholar 

  90. Sun J, Hartvigsen K, Chou MY, Zhang Y, Sukhova GK, Zhang J et al (2010) Deficiency of antigen-presenting cell invariant chain reduces atherosclerosis in mice. Circulation 122(8):808–820

    PubMed  CAS  Google Scholar 

  91. Xu Q, Kleindienst R, Schett G, Waitz W, Jindal S, Gupta RS et al (1996) Regression of arteriosclerotic lesions induced by immunization with heat shock protein 65-containing material in normocholesterolemic, but not hypercholesterolemic, rabbits. Atherosclerosis 123(1–2):145–155

    PubMed  CAS  Google Scholar 

  92. Shoenfeld Y, Harats D, George J (2000) Heat shock protein 60/65, beta 2-glycoprotein I and oxidized LDL as players in murine atherosclerosis. J Autoimmun 15(2):199–202

    PubMed  CAS  Google Scholar 

  93. Foteinos G, Afzal AR, Mandal K, Jahangiri M, Xu Q (2005) Anti-heat shock protein 60 autoantibodies induce atherosclerosis in apolipoprotein E-deficient mice via endothelial damage. Circulation 112(8):1206–1213

    PubMed  CAS  Google Scholar 

  94. Mayr M, Metzler B, Kiechl S, Willeit J, Schett G, Xu Q et al (1999) Endothelial cytotoxicity mediated by serum antibodies to heat shock proteins of escherichia coli and chlamydia pneumoniae: immune reactions to heat shock proteins as a possible link between infection and atherosclerosis. Circulation 99(12):1560–1566

    PubMed  CAS  Google Scholar 

  95. Schett G, Xu Q, Amberger A, Van der Zee R, Recheis H, Willeit J et al (1995) Autoantibodies against heat shock protein 60 mediate endothelial cytotoxicity. J Clin Invest 96(6):2569–2577

    PubMed  CAS  Google Scholar 

  96. Harats D, Yacov N, Gilburd B, Shoenfeld Y, George J (2002) Oral tolerance with heat shock protein 65 attenuates Mycobacterium tuberculosis-induced and high-fat-diet-driven atherosclerotic lesions. J Am Coll Cardiol 40(7):1333–1338

    PubMed  CAS  Google Scholar 

  97. Huber SA, Sakkinen P, David C, Newell MK, Tracy RP (2001) T helper-cell phenotype regulates atherosclerosis in mice under conditions of mild hypercholesterolemia. Circulation 103(21):2610–2616

    PubMed  CAS  Google Scholar 

  98. Maron R, Sukhova G, Faria AM, Hoffmann E, Mach F, Libby P et al (2002) Mucosal administration of heat shock protein-65 decreases atherosclerosis and inflammation in aortic arch of low-density lipoprotein receptor-deficient mice. Circulation 106(13):1708–1715

    PubMed  CAS  Google Scholar 

  99. Cobelens PM, Heijnen CJ, Nieuwenhuis EE, Kramer PP, van der Zee R, van Eden W et al (2000) Treatment of adjuvant-induced arthritis by oral administration of mycobacterial Hsp65 during disease. Arthritis Rheum 43(12):2694–2702

    PubMed  CAS  Google Scholar 

  100. Prakken BJ, Samodal R, Le TD, Giannoni F, Yung GP, Scavulli J et al (2004) Epitope-specific immunotherapy induces immune deviation of proinflammatory T cells in rheumatoid arthritis. Proc Natl Acad Sci USA 101(12):4228–4233

    PubMed  CAS  Google Scholar 

  101. Albani S, Tuckwell JE, Esparza L, Carson DA, Roudier J (1992) The susceptibility sequence to rheumatoid arthritis is a cross-reactive B cell epitope shared by the Escherichia coli heat shock protein dnaJ and the histocompatibility leukocyte antigen DRB10401 molecule. J Clin Invest 89(1):327–331

    PubMed  CAS  Google Scholar 

  102. Fox DA (1997) The role of T cells in the immunopathogenesis of rheumatoid arthritis: new perspectives. Arthritis Rheum 40(4):598–609

    PubMed  CAS  Google Scholar 

  103. Nepom GT, Byers P, Seyfried C, Healey LA, Wilske KR, Stage D et al (1989) HLA genes associated with rheumatoid arthritis. Identification of susceptibility alleles using specific oligonucleotide probes. Arthritis Rheum 32(1):15–21

    PubMed  CAS  Google Scholar 

  104. van Puijvelde GH, van Es T, van Wanrooij EJ, Habets KL, de Vos P, van der Zee R et al (2007) Induction of oral tolerance to HSP60 or an HSP60-peptide activates T cell regulation and reduces atherosclerosis. Arterioscler Thromb Vasc Biol 27(12):2677–2683

    PubMed  Google Scholar 

  105. Xiong Q, Li J, Jin L, Liu J, Li T (2009) Nasal immunization with heat shock protein 65 attenuates atherosclerosis and reduces serum lipids in cholesterol-fed wild-type rabbits probably through different mechanisms. Immunol Lett 125(1):40–45

    PubMed  CAS  Google Scholar 

  106. Elias D, Cohen IR (1996) The hsp60 peptide p277 arrests the autoimmune diabetes induced by the toxin streptozotocin. Diabetes 45(9):1168–1172

    PubMed  CAS  Google Scholar 

  107. Jin L, Zhu A, Wang Y, Chen Q, Xiong Q, Li J et al (2008) A Th1-recognized peptide P277, when tandemly repeated, enhances a Th2 immune response toward effective vaccines against autoimmune diabetes in nonobese diabetic mice. J Immunol 180(1):58–63

    PubMed  CAS  Google Scholar 

  108. Van Eden W, Wick G, Albani S, Cohen I (2007) Stress, heat shock proteins, and autoimmunity: how immune responses to heat shock proteins are to be used for the control of chronic inflammatory diseases. Ann N Y Acad Sci 1113:217–237

    PubMed  Google Scholar 

  109. Thompson SJ, Butcher PD, Patel VK, Rook GA, Stanford J, van der Zee R et al (1991) Modulation of pristane-induced arthritis by mycobacterial antigens. Autoimmunity 11(1):35–43

    PubMed  CAS  Google Scholar 

  110. Quintana FJ, Carmi P, Mor F, Cohen IR (2004) Inhibition of adjuvant-induced arthritis by DNA vaccination with the 70-kd or the 90-kd human heat-shock protein: immune cross-regulation with the 60-kd heat-shock protein. Arthritis Rheum 50(11):3712–3720

    PubMed  CAS  Google Scholar 

  111. Wieten L, Berlo SE, Ten Brink CB, van Kooten PJ, Singh M, van der Zee R et al (2009) IL-10 is critically involved in mycobacterial HSP70 induced suppression of proteoglycan-induced arthritis. PLoS One 4(1):e4186

    PubMed  Google Scholar 

  112. Lee HJ, Takemoto N, Kurata H, Kamogawa Y, Miyatake S, O’Garra A et al (2000) GATA-3 induces T helper cell type 2 (Th2) cytokine expression and chromatin remodeling in committed Th1 cells. J Exp Med 192(1):105–115

    PubMed  CAS  Google Scholar 

  113. Barrios C, Lussow AR, Van Embden J, Van der Zee R, Rappuoli R, Costantino P et al (1992) Mycobacterial heat-shock proteins as carrier molecules. II: the use of the 70-kDa mycobacterial heat-shock protein as carrier for conjugated vaccines can circumvent the need for adjuvants and Bacillus Calmette Guerin priming. Eur J Immunol 22(6):1365–1372

    PubMed  CAS  Google Scholar 

  114. Liang J, Aihua Z, Yu W, Yong L, Jingjing L (2010) HSP65 serves as an immunogenic carrier for a diabetogenic peptide P277 inducing anti-inflammatory immune response in NOD mice by nasal administration. Vaccine 28(19):3312–3317

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratory of Autoimmunity, Division of Experimental Pathophysiology and Immunology, Biocenter, Innsbruck Medical University, Schöpfstraße 41, A-6020, Innsbruck, Austria

    Cecilia Grundtman

Authors
  1. Cecilia Grundtman
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Cecilia Grundtman .

Editor information

Editors and Affiliations

  1. Medical University Innsbruck, Peter-Mayr-Strasse 4 a, Innsbruck, 6020, Austria

    Georg Wick

  2. Laboratory of Autoimmunity, Division of Experimental Pathophysiology, Biocenter, Innsbruck Medical University, Schöpfstraße 41, Innsbruck, 6020, Austria

    Cecilia Grundtman

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer-Verlag/Wien

About this chapter

Cite this chapter

Grundtman, C. (2012). Vaccination Against Atherosclerosis. In: Wick, G., Grundtman, C. (eds) Inflammation and Atherosclerosis. Springer, Vienna. https://doi.org/10.1007/978-3-7091-0338-8_27

Download citation

Publish with us

Policies and ethics

Search

Navigation