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Atherosclerosis—An Age-dependent Autoimmune Disease

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Handbook on Immunosenescence

With increasing age, various diseases that mostly have their roots earlier in life become clinically manifest and are, therefore, age-dependent diseases. Table 1 lists the most frequent medically as well as the most important diseases from a socioeconomical perspective. However, several age-related diseases often develop in a single patient and this multimorbidity is the major problem in geriatrics that becomes ever more important with increasing life expectancy. Worldwide, cardiovascular diseases and infections are the main causes of death followed by tumours [1]. Interestingly, in the developed world, the costs imposed upon society by treatment of age-related diseases shows a different distribution, i.e., cardiovascular diseases followed by autoimmune diseases and tumours with infections at lower ranks. Among cardiovascular diseases, atherosclerosis is the most important representative leading to the known severe sequelae, i.e., myocardial infarction, stroke and peripheral arterial occlusion. In recent years, increasing experimental and clinical evidence has emerged supporting the concept that inflammatory-immunological processes play a major role in the initiation and progression of atherosclerosis including the hypothesis of a triggering of atherogenesis by microbial-human antigenic crossreactivity as well as bona fide autoimmunity.

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References

  1. WHO (2008) Cardiovascular disease.http://www.who.int/cardiovascular_diseases/en

  2. Williams G (1996) Evolution and healing: the new science of Darwinian medicine. London. Phoenix-Orion Books

    Google Scholar 

  3. Wick G, Jansen-Durr P, Berger P, Blasko I and Grubeck-Loebenstein B (2000) Diseases of aging. Vaccine 18:1567–1583

    PubMed  CAS  Google Scholar 

  4. Wick G, Berger P, Jansen-Durr P, Grubeck-Loebenstein B (2003) A Darwinian-evolutionary concept of age-related diseases. Exp Gerontol 38:13–25

    PubMed  Google Scholar 

  5. Stary HC, Chandler AB, Dinsmore RE, Fuster V, Glagov S, Insull W, Jr., Rosenfeld ME, Schwartz CJ, Wagner WD, Wissler RW (1995) A definition of advanced types of atherosclerotic lesions and a histological classification of atherosclerosis. A report from the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association. Arterioscler Thromb Vasc Biol 15:1512–1531

    PubMed  CAS  Google Scholar 

  6. Quinn MT, Parthasarathy S, Fong LG, Steinberg D (1987) Oxidatively modified low density lipoproteins: a potential role in recruitment and retention of monocyte/macrophages during atherogenesis. Proc Natl Acad Sci U S A 84:2995–2998

    PubMed  CAS  Google Scholar 

  7. Ross R, Glomset JA (1976) The pathogenesis of atherosclerosis (first of two parts). N Engl J Med 295:369–377

    PubMed  CAS  Google Scholar 

  8. Barakat A, Lieu D (2003) Differential responsiveness of vascular endothelial cells to different types of fluid mechanical shear stress. Cell Biochem Biophys 38:323–343

    PubMed  CAS  Google Scholar 

  9. Ross R, Glomset JA (1976) The pathogenesis of atherosclerosis (second of two parts). N Engl J Med 295:420–425

    PubMed  CAS  Google Scholar 

  10. Gimbrone MA, Jr (1995) Vascular endothelium: an integrator of pathophysiologic stimuli in atherosclerosis. Am J Cardiol 75:67B–70B

    PubMed  CAS  Google Scholar 

  11. Witztum JL, Steinberg D (2001) The oxidative modification hypothesis of atherosclerosis: does it hold for humans? Trends Cardiovasc Med 11:93–102

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  13. Nieto FJ (1998) Infections and atherosclerosis: new clues from an old hypothesis? Am J Epidemiol 148:937–948

    PubMed  CAS  Google Scholar 

  14. Libby P, Hansson GK (1991) Involvement of the immune system in human atherogenesis: current knowledge and unanswered questions. Lab Invest 64:5–15

    PubMed  CAS  Google Scholar 

  15. Mayerl C, Lukasser M, Sedivy R, Niederegger H, Seiler R, Wick G (2006) Atherosclerosis research from past to present–on the track of two pathologists with opposing views, Carl von Rokitansky and Rudolf Virchow. Virchows Arch 449:96–103

    PubMed  Google Scholar 

  16. Kol A, Bourcier T, Lichtman AH, Libby P (1999) Chlamydial and human heat shock protein 60s activate human vascular endothelium, smooth muscle cells, and macrophages. J Clin Invest 103:571–577

    PubMed  CAS  Google Scholar 

  17. Kleindienst R, Xu Q, Willeit J, Waldenberger FR, Weimann S, Wick G (1993) Immunology of atherosclerosis. Demonstration of heat shock protein 60 expression and T lymphocytes bearing alpha/beta or gamma/delta receptor in human atherosclerotic lesions. Am J Pathol 142:1927–1937

    PubMed  CAS  Google Scholar 

  18. Xu QB, Oberhuber G, Gruschwitz M, Wick G (1990) Immunology of atherosclerosis: cellular composition and major histocompatibility complex class II antigen expression in aortic intima, fatty streaks, and atherosclerotic plaques in young and aged human specimens. Clin Immunol Immunopathol 56:344–359

    PubMed  CAS  Google Scholar 

  19. Metzler B, Xu Q (1997) The role of mast cells in atherosclerosis. Int Arch Allergy Immunol. 114:10–14

    PubMed  CAS  Google Scholar 

  20. Terplan KL, Witebsky E, Rose NR, Paine JR, Egan RW (1960) Experimental thyroiditis in rabbits, guinea pigs and dogs, following immunization with thyroid extracts of their own and of heterologous species. Am J Pathol 36:213–239

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  22. 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 91:2693–2702

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  24. Wick G, Kleindienst R, Dietrich H, Xu Q (1992) Is atherosclerosis an autoimmune disease. Trends Food Sci Tech 3:114–119

    CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  26. Xu Q, Kiechl S, Mayr M, Metzler B, Egger G, Oberhollenzer F, Willeit J, Wick G (1999) Association of serum antibodies to heat-shock protein 65 with carotid atherosclerosis : clinical significance determined in a follow-up study. Circulation 100:1169–1174

    PubMed  CAS  Google Scholar 

  27. Craig EA, Gambill BD, Nelson RJ (1993) Heat shock proteins: molecular chaperones of protein biogenesis. Microbiol Rev 57:402–414

    PubMed  CAS  Google Scholar 

  28. Bernhard D, Moser C, Backovic A, Wick G (2007) Cigarette smoke–an aging accelerator? Exp Gerontol 42:160–165

    PubMed  CAS  Google Scholar 

  29. Amberger A, Maczek C, Jurgens G, Michaelis D, Schett G, Trieb K, Eberl T, Jindal S, Xu Q, Wick G (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 2:94–103

    PubMed  CAS  Google Scholar 

  30. Hochleitner BW, Hochleitner EO, Obrist P, Eberl T, Amberger A, Xu Q, Margreiter R, Wick G (2000) Fluid shear stress induces heat shock protein 60 expression in endothelial cells in vitro and in vivo. Arterioscler Thromb Vasc Biol 20:617–623

    PubMed  CAS  Google Scholar 

  31. Santoro MG (2000) Heat shock factors and the control of the stress response. Biochem Pharmacol 59:55–63

    PubMed  CAS  Google Scholar 

  32. Nollen EA, Morimoto RI (2002) Chaperoning signaling pathways: molecular chaperones as stress-sensing ‘heat shock’ proteins. J Cell Sci 115:2809–2816

    PubMed  CAS  Google Scholar 

  33. Morimoto RI (1993) Cells in stress: transcriptional activation of heat shock genes. Science 259:1409–1410

    PubMed  CAS  Google Scholar 

  34. Res PC, Schaar CG, Breedveld FC, van Eden W, van Emden JD, Cohen IR, de Vries RR (1988) Synovial fluid T cell reactivity against 65 kD heat shock protein of mycobacteria in early chronic arthritis. Lancet 2:478–480

    PubMed  CAS  Google Scholar 

  35. Gaston JS, Life PF, Jenner PJ, Colston MJ, Bacon PA (1990) Recognition of a mycobacteria-specific epitope in the 65-kD heat-shock protein by synovial fluid-derived T cell clones. J Exp Med 171:831–841

    PubMed  CAS  Google Scholar 

  36. Wucherpfennig KW, Newcombe J, Li H, Keddy C, Cuzner ML, Hafler DA (1992) Gamma delta T-cell receptor repertoire in acute multiple sclerosis lesions. Proc Natl Acad Sci U S A 89:4588–4592

    PubMed  CAS  Google Scholar 

  37. Elias D, Markovits D, Reshef T, van der Zee R, Cohen IR (1990) Induction and therapy of autoimmune diabetes in the non-obese diabetic (NOD/Lt) mouse by a 65-kDa heat shock protein. Proc Natl Acad Sci U S A 87:1576–1580

    PubMed  CAS  Google Scholar 

  38. Child DF, Smith CJ, Williams CP (1993) Heat shock protein and the double insult theory for the development of insulin dependent diabetes. J R Soc Med 86:217–219

    PubMed  CAS  Google Scholar 

  39. Crouse JR, Toole JF, McKinney WM, Dignan MB, Howard G, Kahl FR, McMahan MR, Harpold GH (1987) Risk factors for extracranial carotid artery atherosclerosis. Stroke 18:990–996

    PubMed  CAS  Google Scholar 

  40. Simon A, Giral P, Levenson J (1995) Extracoronary atherosclerotic plaque at multiple sites and total coronary calcification deposit in asymptomatic men. Association with coronary risk profile. Circulation 92:1414–1421

    PubMed  CAS  Google Scholar 

  41. Cupples LA, Gagnon DR, Wong ND, Ostfeld AM, Kannel WB (1993) Preexisting cardiovascular conditions and long-term prognosis after initial myocardial infarction: the Framingham Study. Am Heart J 125:863–872

    PubMed  CAS  Google Scholar 

  42. O’Leary DH, Anderson KM, Wolf PA, Evans JC, Poehlman HW (1992) Cholesterol and carotid atherosclerosis in older persons: the Framingham Study. Ann Epidemiol 2:147–153

    PubMed  CAS  Google Scholar 

  43. Witteman JC, Kannel WB, Wolf PA, Grobbee DE, Hofman A, D’Agostino RB, Cobb JC (1990) Aortic calcified plaques and cardiovascular disease (the Framingham Study). Am J Cardiol 66:1060–1064

    PubMed  CAS  Google Scholar 

  44. Garcia-Cardena G, Comander J, Anderson KR, Blackman BR, Gimbrone MA, Jr (2001) Biomechanical activation of vascular endothelium as a determinant of its functional phenotype. Proc Natl Acad Sci U S A 98:4478–4485

    PubMed  CAS  Google Scholar 

  45. Hammond EC, Horn D (1958) Smoking and death rates: report on forty-four months of follow- up of 187,783 men. II. Death rate by cause. JAMA 166:1294–1308

    Google Scholar 

  46. Black HR, JH Laragh, Brenner BM (1995) Smoking and cardiovascular disease in hypertension: pathophysiology, diagnosis and management. New York, NY. Raven Press Ltd, 2621–2647

    Google Scholar 

  47. Knoflach M, Kiechl S, Kind M, Said M, Sief R, Gisinger M, Van Der Zee R, Gaston H, Jarosch E, Willeit J, Wick G (2003) Cardiovascular Risk Factors and Atherosclerosis in Young Males: ARMY Study (Atherosclerosis Risk-Factors in Male Youngsters). Circulation 108:1064–1069

    PubMed  Google Scholar 

  48. Bernhard D, Csordas A, Henderson B, Rossmann A, Kind M, Wick G (2005) Cigarette smoke metal-catalyzed protein oxidation leads to vascular endothelial cell contraction by depolymerization of microtubules. Faseb J 19:1096–1107

    PubMed  CAS  Google Scholar 

  49. Wick G, Henderson B, Knoflach M, Mayr A, Bernhard D (2006). Atherosclerosis: autoimmunity to Heat-Shock Proteins in The Autoimmune Diseases. Rose R, Mackay IR (Eds) New York. Elsevier Academic Press 889–897

    Google Scholar 

  50. Matsuura E, Kobayashi K, Inoue K, Lopez LR, Shoenfeld Y (2005) Oxidized LDL/beta2-glycoprotein I complexes: new aspects in atherosclerosis. Lupus 14:736–741

    PubMed  CAS  Google Scholar 

  51. Galle J, Hansen-Hagge T, Wanner C, Seibold S (2006) Impact of oxidized low density lipoprotein on vascular cells. Atherosclerosis 185:219–226

    PubMed  CAS  Google Scholar 

  52. Seitz CS, Kleindienst R, Xu Q, Wick G (1996) Coexpression of heat-shock protein 60 and intercellular-adhesion molecule-1 is related to increased adhesion of monocytes and T cells to aortic endothelium of rats in response to endotoxin. Lab Invest 74:241–252

    PubMed  CAS  Google Scholar 

  53. Henderson BR, Pfister G, Boeck G, Kind M, Wick G (2003) Expression levels of heat shock protein 60 in human endothelial cells in vitro are unaffected by exposure to 50 Hz magnetic fields. Cell Stress Chaperones 8:172–182

    PubMed  CAS  Google Scholar 

  54. Henderson B, Kind M, Boeck G, Helmberg A, Wick G (2006) Gene expression profiling of human endothelial cells exposed to 50-Hz magnetic fields fails to produce regulated candidate genes. Cell Stress Chaperones 11:227–232

    PubMed  CAS  Google Scholar 

  55. Henderson B, Tagwerker A, Mayrl C, Pfister G, Boeck G, Ulmer H, Dietrich H, Wick G (2003) Progression of arteriovenous bypass restenosis in mice exposed to a 50 Hz magnetic field. Cell Stress Chaperones 8:373–380

    PubMed  Google Scholar 

  56. Robertson AK, Hansson GK (2006) T cells in atherogenesis: for better or for worse? Arterioscler Thromb Vasc Biol 26:2421–2432

    PubMed  CAS  Google Scholar 

  57. Xu Q, Willeit J, Marosi M, Kleindienst R, Oberhollenzer F, Kiechl S, Stulnig T, Luef G, Wick G (1993) Association of serum antibodies to heat-shock protein 65 with carotid atherosclerosis. Lancet 341:255–259

    PubMed  CAS  Google Scholar 

  58. Metzler B, Schett G, Kleindienst R, Van Der Zee R, Ottenhoff T, Hajeer A, Bernstein R, Xu Q, Wick G (1997) Epitope specificity of anti-heat shock protein 65/60 serum antibodies in atherosclerosis. Arterioscler Thromb Vasc Biol 17:536–541

    PubMed  CAS  Google Scholar 

  59. Mayr M, Metzler B, Kiechl S, Willeit J, Schett G, Xu Q, Wick G (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 99:1560–1566

    PubMed  CAS  Google Scholar 

  60. Perschinka H, Wellenzohn B, Parson W, Van Der Zee R, Willeit J, Kiechl S, Wick G (2007) Identification of atherosclerosis-associated conformational heat shock protein 60 epitopes by phage display and structural alignment. Atherosclerosis 194:79–84

    PubMed  Google Scholar 

  61. Perschinka H, Mayr M, Millonig G, Mayerl C, Van Der Zee R, Morrison SG, Morrison RP, Xu Q, Wick G (2003) Cross-reactive B-cell epitopes of microbial and human heat shock protein 60/65 in atherosclerosis. Arterioscler Thromb Vasc Biol 23:1060–1065

    PubMed  CAS  Google Scholar 

  62. Chan YC, Shukla N, Abdus-Samee M, Berwanger CS, Stanford J, Singh M, Mansfield AO, Stansby G (1999) Anti-heat-shock protein 70 kDa antibodies in vascular patients. Eur J Vasc Endovasc Surg 18:381–385

    PubMed  CAS  Google Scholar 

  63. Xu Q, Schett G, Perschinka H, Mayr M, Egger G, Oberhollenzer F, Willeit J, Kiechl S, Wick G (2000) Serum soluble heat shock protein 60 is elevated in subjects with atherosclerosis in a general population. Circulation 102:14–20

    PubMed  CAS  Google Scholar 

  64. Martin-Ventura JL, Duran MC, Blanco-Colio LM, Meilhac O, Leclercq A, Michel J-B, Jensen ON, Hernandez-Merida S, Tunon J, Vivanco F, Egido J (2004) Identification by a Differential Proteomic Approach of Heat Shock Protein 27 as a Potential Marker of Atherosclerosis. Circulation 110:2216–2219

    PubMed  CAS  Google Scholar 

  65. Zhu J, Quyyumi AA, Wu H, Csako G, Rott D, Zalles-Ganley A, Ogunmakinwa J, Halcox J, Epstein SE (2003) Increased Serum Levels of Heat Shock Protein 70 Are Associated With Low Risk of Coronary Artery Disease. Arterioscler Thromb Vasc Biol 23:1055–1059

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  67. Lehtimaki T, Lehtinen S, Solakivi T, Nikkila M, Jaakkola O, Jokela H, Yla-Herttuala S, Luoma JS, Koivula T, Nikkari T (1999) Autoantibodies against oxidized low density lipoprotein in patients with angiographically verified coronary artery disease. Arterioscler Thromb Vasc Biol 19:23–27

    PubMed  CAS  Google Scholar 

  68. Salonen JT, Yla-Herttuala S, Yamamoto R, Butler S, Korpela H, Salonen R, Nyyssonen K, Palinski W, Witztum JL (1992) Autoantibody against oxidised LDL and progression of carotid atherosclerosis. Lancet 339:883–887

    PubMed  CAS  Google Scholar 

  69. Sherer Y, Tenenbaum A, Praprotnik S, Shemesh J, Blank M, Fisman EZ, Harats D, George J, Levy Y, Peter JB, Motro M, Shoenfeld Y (2001) Coronary artery disease but not coronary calcification is associated with elevated levels of cardiolipin, beta-2-glycoprotein-I, and oxidized LDL antibodies. Cardiology 95:20–24

    PubMed  CAS  Google Scholar 

  70. George J, Afek A, Gilburd B, Levkovitz H, Shaish A, Goldberg I, Kopolovic Y, Wick G, Shoenfeld Y, Harats D (1998) Hyperimmunization of apo-E-deficient mice with homologous malondialdehyde low-density lipoprotein suppresses early atherogenesis. Atherosclerosis 138:147–152

    PubMed  CAS  Google Scholar 

  71. George J, Harats D, Gilburd B, Afek A, Levy Y, Schneiderman J, Barshack I, Kopolovic J, Shoenfeld Y (1999) Immunolocalization of beta2-glycoprotein I (apolipoprotein H) to human atherosclerotic plaques: potential implications for lesion progression. Circulation 99:2227–2230

    PubMed  CAS  Google Scholar 

  72. Vaarala O, Manttari M, Manninen V, Tenkanen L, Puurunen M, Aho K, Palosuo T (1995) Anti-cardiolipin antibodies and risk of myocardial infarction in a prospective cohort of middle-aged men. Circulation 91:23–27

    PubMed  CAS  Google Scholar 

  73. Zhou X, Nicoletti A, Elhage R, Hansson GK (2000) Transfer of CD4(+) T cells aggravates atherosclerosis in immunodeficient apolipoprotein E knockout mice. Circulation 102:2919–2922

    PubMed  CAS  Google Scholar 

  74. 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 103:2610–2616

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  76. Metzler B, Mayr M, Dietrich H, Singh M, Wiebe E, Xu Q, Wick G (2001) Correction. Arteriosclerosis, Thrombosis, and Vascular Biology 21:1706

    CAS  Google Scholar 

  77. Gupta S, Pablo AM, Jiang X, Wang N, Tall AR, Schindler C (1997) IFN-gamma potentiates atherosclerosis in ApoE knock-out mice. J Clin Invest 99:2752–2761

    PubMed  CAS  Google Scholar 

  78. Buono C, Come CE, Stavrakis G, Maguire GF, Connelly PW, Lichtman AH (2003) Influence of interferon-gamma on the extent and phenotype of diet-induced atherosclerosis in the LDLR-deficient mouse. Arterioscler Thromb Vasc Biol 23:454–460

    PubMed  CAS  Google Scholar 

  79. 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 163:1117–1125

    PubMed  CAS  Google Scholar 

  80. Elhage R, Jawien J, Rudling M, Ljunggren HG, Takeda K, Akira S, Bayard F, Hansson GK (2003) Reduced atherosclerosis in interleukin-18 deficient apolipoprotein E-knockout mice. Cardiovasc Res 59:234–240

    PubMed  CAS  Google Scholar 

  81. Branen L, Hovgaard L, Nitulescu M, Bengtsson E, Nilsson J, Jovinge S (2004) Inhibition of tumor necrosis factor-alpha reduces atherosclerosis in apolipoprotein E knockout mice. Arterioscler Thromb Vasc Biol 24:2137–2142

    PubMed  CAS  Google Scholar 

  82. Born W, Harbeck R, O’Brien RL (1991) Possible links between immune system and stress response: the role of gamma delta T lymphocytes. Semin Immunol 3:43–48

    PubMed  CAS  Google Scholar 

  83. Elhage R, Gourdy P, Brouchet L, Jawien J, Fouque M-J, Fievet C, Huc X, Barreira Y, Couloumiers JC, Arnal J-F, Bayard F (2004) Deleting TCR{alpha}{beta}+ or CD4+ T Lymphocytes Leads to Opposite Effects on Site-Specific Atherosclerosis in Female Apolipoprotein E-Deficient Mice. Am J Pathol 165:2013–2018

    PubMed  Google Scholar 

  84. Bobryshev YV, Lord RS (1995) Ultrastructural recognition of cells with dendritic cell morphology in human aortic intima. Contacting interactions of Vascular Dendritic Cells in athero-resistant and athero-prone areas of the normal aorta. Arch Histol Cytol 58:307–322

    PubMed  CAS  Google Scholar 

  85. De Palma R, Del Galdo F, Abbate G, Chiariello M, Calabro R, Forte L, Cimmino G, Papa MF, Russo MG, Ambrosio G, Giombolini C, Tritto I, Notaristefano S, Berrino L, Rossi F, Golino P (2006) Patients with acute coronary syndrome show oligoclonal T-cell recruitment within unstable plaque: evidence for a local, intracoronary immunologic mechanism. Circulation 113:640–646

    PubMed  Google Scholar 

  86. Liuzzo G, Goronzy JJ, Yang H, Kopecky SL, Holmes DR, Frye RL, Weyand CM (2000) Monoclonal T-cell proliferation and plaque instability in acute coronary syndromes. Circulation 101:2883–2888

    PubMed  CAS  Google Scholar 

  87. Rossmann A, Henderson B, Heidecker B, Seiler R, Fraedrich G, Singh M, Parson W, Keller M, Grubeck-Loebenstein B, Wick G (2007) T-cells from advanced atherosclerotic lesions recognize hHSP60 and have a restricted T-cell receptor repertoire. Exp Gerontol, Epub ahead of print

    Google Scholar 

  88. Benagiano M, D’Elios MM, Amedei A, Azzurri A, van de Zee R, Ciervo A, Rombola G, Romagnani S, Cassone A, Del Prete G (2005) Human 60-kDa heat shock protein is a target autoantigen of T cells derived from atherosclerotic plaques. J Immunol 174:6509–6517

    PubMed  CAS  Google Scholar 

  89. Choi JI, Chung SW, Kang HS, Rhim BY, Kim SJ (2002) Establishment of Porphyromonas gingivalis heat-shock-protein-specific T-cell lines from atherosclerosis patients. J Dent Res 81:344–348

    PubMed  Google Scholar 

  90. Mosorin M, Surcel HM, Laurila A, Lehtinen M, Karttunen R, Juvonen J, Paavonen J, Morrison RP, Saikku P, Juvonen T (2000) Detection of Chlamydia pneumoniae-reactive T lymphocytes in human atherosclerotic plaques of carotid artery. Arterioscler Thromb Vasc Biol 20:1061–1067

    PubMed  CAS  Google Scholar 

  91. 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 U S A 92:3893–3897

    PubMed  CAS  Google Scholar 

  92. Epstein SE, Zhou YF, Zhu J (1999) Infection and atherosclerosis: emerging mechanistic paradigms. Circulation 100:E20–E28

    PubMed  CAS  Google Scholar 

  93. Millonig G, Malcom GT, Wick G (2002) Early inflammatory-immunological lesions in juvenile atherosclerosis from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY)-study. Atherosclerosis 160:441–448

    PubMed  CAS  Google Scholar 

  94. Whitman SC, Rateri DL, Szilvassy SJ, Yokoyama W, Daugherty A (2004) Depletion of natural killer cell function decreases atherosclerosis in low-density lipoprotein receptor null mice. Arterioscler Thromb Vasc Biol 24:1049–1054

    PubMed  CAS  Google Scholar 

  95. Major AS, Wilson MT, McCaleb JL, Ru SY, Stanic AK, Joyce S, Van Kaer L, Fazio S, Linton MF (2004) Quantitative and qualitative differences in proatherogenic NKT cells in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol 24:2351–2357

    PubMed  CAS  Google Scholar 

  96. Tupin E, Nicoletti A, Elhage R, Rudling M, Ljunggren HG, Hansson GK, Berne GP (2004) CD1d-dependent activation of NKT cells aggravates atherosclerosis. J Exp Med 199:417–422

    PubMed  CAS  Google Scholar 

  97. Nakai Y, Iwabuchi K, Fujii S, Ishimori N, Dashtsoodol N, Watano K, Mishima T, Iwabuchi C, Tanaka S, Bezbradica JS, Nakayama T, Taniguchi M, Miyake S, Yamamura T, Kitabatake A, Joyce S, Van Kaer L, Onoe K (2004) Natural killer T cells accelerate atherogenesis in mice. Blood 104:2051–2059

    PubMed  CAS  Google Scholar 

  98. Lipscomb MF, Masten BJ (2002) Dendritic cells: immune regulators in health and disease. Physiol Rev 82:97–130

    PubMed  CAS  Google Scholar 

  99. Steinman RM, Hawiger D, Nussenzweig MC (2003) Tolerogenic dendritic cells. Annu Rev Immunol 21:685–711

    PubMed  CAS  Google Scholar 

  100. Heath WR, Belz GT, Behrens GM, Smith CM, Forehan SP, Parish IA, Davey GM, Wilson NS, Carbone FR, Villadangos JA (2004) Cross-presentation, dendritic cell subsets, and the generation of immunity to cellular antigens. Immunol Rev 199:9–26

    PubMed  CAS  Google Scholar 

  101. de Jong EC, Smits HH, Kapsenberg ML (2005) Dendritic cell-mediated T cell polarization. Springer Semin Immunopathol 26:289–307

    PubMed  Google Scholar 

  102. Morel PA, Feili-Hariri M, Coates PT, Thomson AW (2003) Dendritic cells, T cell tolerance and therapy of adverse immune reactions. Clin Exp Immunol 133:1–10

    PubMed  CAS  Google Scholar 

  103. Millonig G, Niederegger H, Rabl W, Hochleitner BW, Hoefer D, Romani N, Wick G (2001) Network of vascular-associated dendritic cells in intima of healthy young individuals. Arterioscler Thromb Vasc Biol 21:503–508

    PubMed  CAS  Google Scholar 

  104. Bobryshev YV, Lord RS (1998) Mapping of vascular dendritic cells in atherosclerotic arteries suggests their involvement in local immune-inflammatory reactions. Cardiovasc Res 37:799–810

    PubMed  CAS  Google Scholar 

  105. Lord RS, Bobryshev YV (1999) Clustering of dendritic cells in athero-prone areas of the aorta. Atherosclerosis 146:197–198

    PubMed  CAS  Google Scholar 

  106. Banchereau J, Steinman RM (1998) Dendritic cells and the control of immunity. Nature 392:245–252

    PubMed  CAS  Google Scholar 

  107. Chen Y, Kuchroo VK, Inobe J, Hafler DA, Weiner HL (1994) Regulatory T cell clones induced by oral tolerance: suppression of autoimmune encephalomyelitis. Science 265:1237–1240

    PubMed  CAS  Google Scholar 

  108. Levings MK, Sangregorio R, Roncarolo MG (2001) Human cd25(+)cd4(+) t regulatory cells suppress naive and memory T cell proliferation and can be expanded in vitro without loss of function. J Exp Med 193:1295–1302

    PubMed  CAS  Google Scholar 

  109. Ait-Oufella H, Salomon BL, Potteaux S, Robertson AK, Gourdy P, Zoll J, Merval R, Esposito B, Cohen JL, Fisson S, Flavell RA, Hansson GK, Klatzmann D, Tedgui A, Mallat Z (2006) Natural regulatory T cells control the development of atherosclerosis in mice. Nat Med 12:178–180

    PubMed  CAS  Google Scholar 

  110. Mor A, Planer D, Luboshits G, Afek A, Metzger S, Chajek-Shaul T, Keren G, George J (2007) Role of Naturally Occurring CD4+CD25+ Regulatory T Cells in Experimental Atherosclerosis. Arterioscler Thromb Vasc Biol 27:893–900

    PubMed  CAS  Google Scholar 

  111. Mor A, Luboshits G, Planer D, Keren G, George J (2006) Altered status of CD4+CD25+regulatory T cells in patients with acute coronary syndromes. Eur Heart J 27:2530–2537

    PubMed  CAS  Google Scholar 

  112. Yang K, Li D, Luo M, Hu Y (2006) Generation of HSP60-specific regulatory T cell and effect on atherosclerosis. Cell Immunol 243:90–95

    PubMed  CAS  Google Scholar 

  113. 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 40:1333–1338

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  115. Stary HC (1980) The intimal macrophage in atherosclerosis. Artery 8:205–207

    PubMed  CAS  Google Scholar 

  116. Stary HC, Chandler AB, Glagov S, Guyton JR, Insull W, Jr., Rosenfeld ME, Schaffer SA, Schwartz CJ, Wagner WD, Wissler RW (1994) A definition of initial, fatty streak, and intermediate lesions of atherosclerosis. A report from the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association. Arterioscler Thromb 14:840–856

    PubMed  CAS  Google Scholar 

  117. Schonbeck U, Gerdes N, Varo N, Reynolds RS, Horton DB, Bavendiek U, Robbie L, Ganz P, Kinlay S, Libby P (2002) Oxidized low-density lipoprotein augments and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors limit CD40 and CD40L expression in human vascular cells. Circulation 106:2888–2893

    PubMed  Google Scholar 

  118. Ramprasad MP, Terpstra V, Kondratenko N, Quehenberger O, Steinberg D (1996) Cell surface expression of mouse macrosialin and human CD68 and their role as macrophage receptors for oxidized low density lipoprotein. Proc Natl Acad Sci U S A 93:14833–14838

    PubMed  CAS  Google Scholar 

  119. Kume N, Murase T, Moriwaki H, Aoyama T, Sawamura T, Masaki T, Kita T (1998) Inducible expression of lectin-like oxidized LDL receptor-1 in vascular endothelial cells. Circ Res 83:322–327

    PubMed  CAS  Google Scholar 

  120. Moreau M, Brocheriou I, Petit L, Ninio E, Chapman MJ, Rouis M (1999) Interleukin-8 mediates downregulation of tissue inhibitor of metalloproteinase-1 expression in cholesterolloaded human macrophages: relevance to stability of atherosclerotic plaque. Circulation 99:420–426

    PubMed  CAS  Google Scholar 

  121. Hansson GK, Libby P (2006) The immune response in atherosclerosis: a double-edged sword. Nat Rev Immunol 6:508–519 (Epub 2006 Jun 2016)

    PubMed  CAS  Google Scholar 

  122. Yuan XM, Brunk UT, Olsson AG (1995) Effects of iron- and hemoglobin-loaded human monocyte-derived macrophages on oxidation and uptake of LDL. Arterioscler Thromb Vasc Biol 15:1345–1351

    PubMed  CAS  Google Scholar 

  123. Fadok VA, Bratton DL, Konowal A, Freed PW, Westcott JY, Henson PM (1998) Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine/paracrine mechanisms involving TGF-beta, PGE2, and PAF. J Clin Invest 101:890–898

    PubMed  CAS  Google Scholar 

  124. Savill J, Fadok V (2000) Corpse clearance defines the meaning of cell death. Nature 407:784–788

    PubMed  CAS  Google Scholar 

  125. Grainger DJ, Reckless J, McKilligin E (2004) Apolipoprotein E modulates clearance of apoptotic bodies in vitro and in vivo, resulting in a systemic proinflammatory state in apolipoprotein E-deficient mice. J Immunol 173:6366–6375

    PubMed  CAS  Google Scholar 

  126. Chung EY, Kim SJ, Ma XJ (2006) Regulation of cytokine production during phagocytosis of apoptotic cells. Cell Res 16:154–161

    PubMed  CAS  Google Scholar 

  127. Boisvert WA, Rose DM, Boullier A, Quehenberger O, Sydlaske A, Johnson KA, Curtiss LK, Terkeltaub R (2006) Leukocyte transglutaminase 2 expression limits atherosclerotic lesion size. Arterioscler Thromb Vasc Biol 26:563–569

    PubMed  CAS  Google Scholar 

  128. Aprahamian T, Rifkin I, Bonegio R, Hugel B, Freyssinet JM, Sato K, Castellot JJ, Jr., Walsh K (2004) Impaired clearance of apoptotic cells promotes synergy between atherogenesis and autoimmune disease. J Exp Med 199:1121–1131

    PubMed  CAS  Google Scholar 

  129. Oksjoki R, Kovanen PT, Meri S, Pentikainen MO (2007) Function and regulation of the complement system in cardiovascular diseases. Front Biosci 12:4696–4708

    PubMed  CAS  Google Scholar 

  130. Vlaicu R, Rus HG, Niculescu F, Cristea A (1985) Immunoglobulins and complement components in human aortic atherosclerotic intima. Atherosclerosis 55:35–50

    PubMed  CAS  Google Scholar 

  131. Seifert PS, Hansson GK (1989) Complement receptors and regulatory proteins in human atherosclerotic lesions. Arteriosclerosis 9:802–811

    PubMed  CAS  Google Scholar 

  132. Oksjoki R, Kovanen PT, Pentikainen MO (2003) Role of complement activation in atherosclerosis. Curr Opin Lipidol 14:477–482

    PubMed  CAS  Google Scholar 

  133. Jonsson G, Truedsson L, Sturfelt G, Oxelius VA, Braconier JH, Sjoholm AG (2005) Hereditary C2 deficiency in Sweden: frequent occurrence of invasive infection, atherosclerosis, and rheumatic disease. Medicine (Baltimore) 84:23–34

    Google Scholar 

  134. Nityanand S, Truedsson L, Mustafa A, Bergmark C, Lefvert AK (1999) Circulating immune complexes and complement C4 null alleles in patients in patients operated on for premature atherosclerotic peripheral vascular disease. J Clin Immunol 19:406–413

    PubMed  CAS  Google Scholar 

  135. Jeziorska M, McCollum C, Woolley DE (1997) Mast cell distribution, activation, and phenotype in atherosclerotic lesions of human carotid arteries. J Pathol 182:115–122

    PubMed  CAS  Google Scholar 

  136. Sun J, Sukhova GK, Wolters PJ, Yang M, Kitamoto S, Libby P, MacFarlane LA, Mallen-St Clair J, Shi GP (2007) Mast cells promote atherosclerosis by releasing proinflammatory cytokines. Nat Med 13:719–724

    PubMed  CAS  Google Scholar 

  137. Anderson KV (2000) Toll signaling pathways in the innate immune response. Curr Opin Immunol 12:13–19

    PubMed  CAS  Google Scholar 

  138. Medzhitov R, Preston-Hurlburt P, Kopp E, Stadlen A, Chen C, Ghosh S, Janeway CA, Jr (1998) MyD88 is an adaptor protein in the hToll/IL-1 receptor family signaling pathways. Mol Cell 2:253–258

    PubMed  CAS  Google Scholar 

  139. Frantz S, Kobzik L, Kim YD, Fukazawa R, Medzhitov R, Lee RT, Kelly RA (1999) Toll4 (TLR4) expression in cardiac myocytes in normal and failing myocardium. J Clin Invest 104:271–280

    PubMed  CAS  Google Scholar 

  140. Akira S, Uematsu S, Takeuchi O (2006) Pathogen recognition and innate immunity. Cell 124:783–801

    PubMed  CAS  Google Scholar 

  141. Re F, Strominger JL (2001) Toll-like receptor 2 (TLR2) and TLR4 differentially activate human dendritic cells. J Biol Chem 276:37692–37699

    PubMed  CAS  Google Scholar 

  142. Edfeldt K, Swedenborg J, Hansson GK, Yan ZQ (2002) Expression of toll-like receptors in human atherosclerotic lesions: a possible pathway for plaque activation. Circulation 105:1158–1161

    PubMed  CAS  Google Scholar 

  143. Xu XH, Shah PK, Faure E, Equils O, Thomas L, Fishbein MC, Luthringer D, Xu XP, Rajavashisth TB, Yano J, Kaul S, Arditi M (2001) Toll-like receptor-4 is expressed by macrophages in murine and human lipid-rich atherosclerotic plaques and upregulated by oxidized LDL. Circulation 104:3103–3108

    PubMed  CAS  Google Scholar 

  144. Schoneveld AH, Hoefer I, Sluijter JP, Laman JD, de Kleijn DP, Pasterkamp G (2007) Atherosclerotic lesion development and Toll like receptor 2 and 4 responsiveness. Atherosclerosis 20:20

    Google Scholar 

  145. Kiechl S, Lorenz E, Reindl M, Wiedermann CJ, Oberhollenzer F, Bonora E, Willeit J, Schwartz DA (2002) Toll-like receptor 4 polymorphisms and atherogenesis. N Engl J Med 347:185–192

    PubMed  CAS  Google Scholar 

  146. Ameziane N, Beillat T, Verpillat P, Chollet-Martin S, Aumont MC, Seknadji P, Lamotte M, Lebret D, Ollivier V, de Prost D (2003) Association of the Toll-like receptor 4 gene Asp299Gly polymorphism with acute coronary events. Arterioscler Thromb Vasc Biol 23: E61–E64

    PubMed  Google Scholar 

  147. Labrum R, Bevan S, Sitzer M, Lorenz M, Markus HS (2007) Toll receptor polymorphisms and carotid artery intima-media thickness. Stroke 38:1179–1184

    PubMed  Google Scholar 

  148. Koch W, Hoppmann P, Pfeufer A, Schomig A, Kastrati A (2006) Toll-like receptor 4 gene polymorphisms and myocardial infarction: no association in a Caucasian population. Eur Heart J 27:2524–2529, (Epub 2006 Sep 2525)

    PubMed  CAS  Google Scholar 

  149. Zee RY, Hegener HH, Gould J, Ridker PM (2005) Toll-like receptor 4 Asp299Gly gene polymorphism and risk of atherothrombosis. Stroke 36:154–157, (Epub 2004 Dec 2002)

    PubMed  CAS  Google Scholar 

  150. Bjorkbacka H, Kunjathoor VV, Moore KJ, Koehn S, Ordija CM, Lee MA, Means T, Halmen K, Luster AD, Golenbock DT, Freeman MW (2004) Reduced atherosclerosis in MyD88-null mice links elevated serum cholesterol levels to activation of innate immunity signaling pathways. Nat Med 10:416–421, (Epub 2004 Mar 2014)

    PubMed  Google Scholar 

  151. Michelsen KS, Wong MH, Shah PK, Zhang W, Yano J, Doherty TM, Akira S, Rajavashisth TB, Arditi M (2004) Lack of Toll-like receptor 4 or myeloid differentiation factor 88 reduces atherosclerosis and alters plaque phenotype in mice deficient in apolipoprotein E. Proc Natl Acad Sci U S A 101:10679–10684, (Epub 12004 Jul 10612)

    PubMed  CAS  Google Scholar 

  152. Mullick AE, Tobias PS, Curtiss LK (2005) Modulation of atherosclerosis in mice by Toll-like receptor 2. J Clin Invest. 115:3149–3156. Epub 2005 Oct 3146

    PubMed  CAS  Google Scholar 

  153. Ohashi K, Burkart V, Flohe S, Kolb H (2000) Cutting edge: heat shock protein 60 is a putative endogenous ligand of the toll-like receptor-4 complex. J Immunol 164:558–561

    PubMed  CAS  Google Scholar 

  154. Vabulas RM, Ahmad-Nejad P, da Costa C, Miethke T, Kirschning CJ, Hacker H, Wagner H (2001) Endocytosed HSP60s Use Toll-like Receptor 2 (TLR2) and TLR4 to Activate the Toll/Interleukin-1 Receptor Signaling Pathway in Innate Immune Cells. J Biol Chem 276:31332–31339

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  157. van Eden W, Hauet-Broere F, Berlo S, Paul L, van der Zee R, de Kleer I, Prakken B, Taams L (2005) Stress proteins as inducers and targets of regulatory T cells in arthritis. Int Rev Immunol 24:181–197

    PubMed  Google Scholar 

  158. van Eden W, Hauet-Broere F, Berlo S, Paul L, van der Zee R, de Kleer I, Prakken B, Taams L (2005) Stress proteins as inducers and targets of regulatory T cells in arthritis. Int Rev Immunol 24:181–197

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Division of Experimental Pathophysiology and Immunology Laboratory of Autoimmunity, Biocenter, Innsbruck Medical University, Fritz-Pregl-Str. 3/IV, Innsbruck, A-6020, Austria

    B. Henderson, A. Rossmann, Ch. Mayerl & G. Wick

  2. Department of Radiology, Innsbruck Medical University, Anichstrasse 35, Innsbruck, A-6020, Austria

    M. Wick

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  1. B. Henderson
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Editors and Affiliations

  1. Research Center on Aging, Department of Medicine, Immunology Graduate Programme, Faculty of Medicine, University of Sherbrooke, 1036 Rue Belvedere, J1H 4C4, Sherbrooke, Quebec, Canada

    Tamas Fulop

  2. Department of Experimental Pathalogy, CIG Interdepartmental Center “L. Galvani” University of Bologna, Via San Giacomo 12, 40126, Bologna, Italy

    Claudio Franceschi

  3. Institute for Health and Life Sciences, 4-6-22 Kohinato, Bunkyo-ku, Tokyo, 112-0006, Japan

    Katsuiku Hirokawa

  4. ZMF - Zentrum Med. Forschung Abt. Transplant./ Immunologie, University of Tübingen, Waldhörnlestr. 22, 72072, Tübingen, Germany

    Graham Pawelec

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Henderson, B., Rossmann, A., Mayerl, C., Wick, M., Wick, G. (2009). Atherosclerosis—An Age-dependent Autoimmune Disease. In: Fulop, T., Franceschi, C., Hirokawa, K., Pawelec, G. (eds) Handbook on Immunosenescence. Springer, Dordrecht. https://doi.org/10.1007/978-1-4020-9063-9_53

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