Modulation of autoimmunity and atherosclerosis - Common targets and promising translational approaches against disease

Circulation Journal

Volumn 79, Issue 5, 2015, Pages 924-933

  Ketelhuth, Daniel F J ^a   Hansson, Göran K ^a  

^a KAROLINSKA UNIVERSITY HOSPITAL   (Sweden)

Author keywords

Atherosclerosis; Autoimmune disease; Cardiovascular disease; Immunomodulation; Therapy

Indexed keywords

APOLIPOPROTEIN B; BETA2 GLYCOPROTEIN 1; C REACTIVE PROTEIN; CALCITRIOL; CD1 ANTIGEN; CHYLOMICRON; FIBRINOGEN; GAMMA INTERFERON; HEAT SHOCK PROTEIN; HUMAN MONOCLONAL ANTIBODY; INTERCELLULAR ADHESION MOLECULE 1; INTERLEUKIN 1; INTERLEUKIN 10; INTERLEUKIN 12; INTERLEUKIN 17; INTERLEUKIN 1BETA; INTERLEUKIN 2; INTERLEUKIN 6; LOW DENSITY LIPOPROTEIN; MATRIX METALLOPROTEINASE; METHOTREXATE; MONOCYTE CHEMOTACTIC PROTEIN 1; PHOSPHORYLCHOLINE; RITUXIMAB; T LYMPHOCYTE RECEPTOR; TRANSFORMING GROWTH FACTOR BETA; TUMOR NECROSIS FACTOR; UNINDEXED DRUG; VASCULAR CELL ADHESION MOLECULE 1; VERY LOW DENSITY LIPOPROTEIN; IMMUNOSUPPRESSIVE AGENT;

ARTICLE; ATHEROSCLEROTIC PLAQUE; AUTOIMMUNITY; B LYMPHOCYTE; CD25+ T LYMPHOCYTE; CD4+ T LYMPHOCYTE; CORONARY ARTERY DISEASE; DISEASE COURSE; HUMAN; HUMORAL IMMUNE DEFICIENCY; IMMUNOMODULATION; MACROPHAGE ACTIVATION; MAJOR HISTOCOMPATIBILITY COMPLEX; NONHUMAN; PHASE 2 CLINICAL TRIAL (TOPIC); REGULATORY T LYMPHOCYTE; RHEUMATOID ARTHRITIS; SIGNAL TRANSDUCTION; ST SEGMENT ELEVATION MYOCARDIAL INFARCTION; VACCINATION; ATHEROSCLEROSIS; IMMUNOLOGY; LUPUS ERYTHEMATOSUS, SYSTEMIC; MYOCARDIAL INFARCTION; PATHOLOGY; STROKE;

ATHEROSCLEROSIS; HUMANS; IMMUNOSUPPRESSIVE AGENTS; LUPUS ERYTHEMATOSUS, SYSTEMIC; MYOCARDIAL INFARCTION; STROKE;

EID: 84928501216     PISSN: 13469843     EISSN: 13474820     Source Type: Journal    
DOI: 10.1253/circj.CJ-15-0167     Document Type: Article

References (158)

1. Nichols M, Townsend N, Scarborough P, Rayner M. Cardiovascular disease in Europe 2014: Epidemiological update. Eur Heart J 2014; 35: 2950-2959.
2. WHO, editor. Global health risks: Mortality and burden of disease attributable to selected major risk factors. Geneva: World Health Organization, 2009.
3. Hansson GK. Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med 2005; 352: 1685-1695.
4. Falk E, Shah PK, Fuster V. Coronary plaque disruption. Circulation 1995; 92: 657-671.
5. Perk J, De Backer G, Gohlke H, Graham I, Reiner Z, Verschuren M, et al. European Guidelines on cardiovascular disease prevention in clinical practice (version 2012): The Fifth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of nine societies and by invited experts): Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). Eur Heart J 2012; 33: 1635-1701.
6. Baigent C, Keech A, Kearney PM, Blackwell L, Buck G, Pollicino C, et al. Efficacy and safety of cholesterol-lowering treatment: Prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet 2005; 366: 1267-1278.
7. Greenland P, Knoll MD, Stamler J, Neaton JD, Dyer AR, Garside DB, et al. Major risk factors as antecedents of fatal and nonfatal coronary heart disease events. JAMA 2003; 290: 891-897.
8. Tabas I, Williams KJ, Boren J. Subendothelial lipoprotein retention as the initiating process in atherosclerosis: Update and therapeutic implications. Circulation 2007; 116: 1832-1844.
9. Oorni K, Pentikainen MO, Ala-Korpela M, Kovanen PT. Aggregation, fusion, and vesicle formation of modified low density lipoprotein particles: Molecular mechanisms and effects on matrix interactions. J Lipid Res 2000; 41: 1703-1714.
10. Steinbrecher UP, Zhang HF, Lougheed M. Role of oxidatively modified LDL in atherosclerosis. Free Radic Biol Med 1990; 9: 155-168.
11. Mallat Z. Macrophages. Arterioscler Thromb Vasc Biol 2014; 34: 2509-2519.
12. Ketelhuth DF, Back M. The role of matrix metalloproteinases in atherothrombosis. Curr Atheroscler Rep 2011; 13: 162-169.
13. Platt AM, Randolph GJ. Dendritic cell migration through the lymphatic vasculature to lymph nodes. Adv Immunol 2013; 120: 51-68.
14. Thurmond RL, Sun S, Karlsson L, Edwards JP. Cathepsin S inhibitors as novel immunomodulators. Curr Opin Investig Drugs 2005; 6: 473-482.
15. Ketelhuth DF, Hansson GK. Cellular immunity, low-density lipoprotein and atherosclerosis: Break of tolerance in the artery wall. Thromb Haemost 2011; 106: 779-786.
16. Blasi C. The autoimmune origin of atherosclerosis. Atherosclerosis 2008; 201: 17-32.
17. Mohanta SK, Yin C, Peng L, Srikakulapu P, Bontha V, Hu D, et al. Artery tertiary lymphoid organs contribute to innate and adaptive immune responses in advanced mouse atherosclerosis. Circ Res 2014; 114: 1772-1787.
18. Clement M, Guedj K, Andreata F, Morvan M, Bey L, Khallou- Laschet J, et al. Control of the T follicular helper-germinal center B-cell axis by CD8+ regulatory T cells limits atherosclerosis and tertiary lymphoid organ development. Circulation 2015; 131: 560-570.
19. Ovchinnikova O, Robertson AK, Wagsater D, Folco EJ, Hyry M, Myllyharju J, et al. T-cell activation leads to reduced collagen maturation in atherosclerotic plaques of Apoe(–/–) mice. Am J Pathol 2009; 174: 693-700.
20. Rose NR, Bona C. Defining criteria for autoimmune diseases (Witebsky’s postulates revisited). Immunol Today 1993; 14: 426-430.
21. Ketelhuth DF, Gisterå A, Johansson DK, Hansson GK. T cell-based therapies for atherosclerosis. Curr Pharm Des 2013; 19: 5850-5858.
22. Zhou X, Robertson AK, Hjerpe C, Hansson GK. Adoptive transfer of CD4+ T cells reactive to modified low-density lipoprotein aggravates atherosclerosis. Arterioscler Thromb Vasc Biol 2006; 26: 864-870.
23. Hermansson A, Ketelhuth DF, Strodthoff D, Wurm M, Hansson EM, Nicoletti A, et al. Inhibition of T cell response to native lowdensity lipoprotein reduces atherosclerosis. J Exp Med 2010; 207: 1081-1093.
24. Ridker PM, Danielson E, Fonseca FA, Genest J, Gotto AM Jr, Kastelein JJ, et al. Reduction in C-reactive protein and LDL cholesterol and cardiovascular event rates after initiation of rosuvastatin: A prospective study of the JUPITER trial. Lancet 2009; 373: 1175-1182.
25. Getts DR, Shankar S, Chastain EM, Martin A, Getts MT, Wood K, et al. Current landscape for T-cell targeting in autoimmunity and transplantation. Immunotherapy 2011; 3: 853-870.
26. Jonasson L, Holm J, Hansson GK. Cyclosporin A inhibits smooth muscle proliferation in the vascular response to injury. Proc Natl Acad Sci USA 1988; 85: 2303-2306.
27. Serruys PW, Kutryk MJ, Ong AT. Coronary-artery stents. N Engl J Med 2006; 354: 483-495.
28. Maradit-Kremers H, Nicola PJ, Crowson CS, Ballman KV, Gabriel SE. Cardiovascular death in rheumatoid arthritis: A populationbased study. Arthritis Rheum 2005; 52: 722-732.
29. Farkouh ME, Greenberg BP. An evidence-based review of the cardiovascular risks of nonsteroidal anti-inflammatory drugs. Am J Cardiol 2009; 103: 1227-1237.
30. Ridker PM. Targeting inflammatory pathways for the treatment of cardiovascular disease. Eur Heart J 2014; 35: 540-543.
31. Moreira DM, Lueneberg ME, da Silva RL, Fattah T, Mascia Gottschall CA. Rationale and design of the TETHYS trial: The effects of methotrexate therapy on myocardial infarction with STsegment elevation. Cardiology 2013; 126: 167-170.
32. Bulgarelli A, Martins Dias AA, Caramelli B, Maranhao RC. Treatment with methotrexate inhibits atherogenesis in cholesterol-fed rabbits. J Cardiovasc Pharmacol 2012; 59: 308-314.
33. Bulgarelli A, Leite AC Jr, Dias AA, Maranhao RC. Anti-atherogenic effects of methotrexate carried by a lipid nanoemulsion that binds to LDL receptors in cholesterol-fed rabbits. Cardiovasc Drugs Ther 2013; 27: 531-539.
34. Roubille C, Richer V, Starnino T, McCourt C, McFarlane A, Fleming P, et al. The effects of tumour necrosis factor inhibitors, methotrexate, non-steroidal anti-inflammatory drugs and corticosteroids on cardiovascular events in rheumatoid arthritis, psoriasis and psoriatic arthritis: A systematic review and meta-analysis. Ann Rheum Dis 2015; 74: 480-489.
35. Liu X, Fang L, Guo TB, Mei H, Zhang JZ. Drug targets in the cytokine universe for autoimmune disease. Trends Immunol 2013; 34: 120-128.
36. Sharma M, Deekshith V, Semwal A, Sriram D, Yogeeswari P. Discovery of fused triazolo-thiadiazoles as inhibitors of TNF-alpha: Pharmacophore hybridization for treatment of neuropathic pain. Pain Ther 2012; 1: 3.
37. Barnabe C, Martin BJ, Ghali WA. Systematic review and metaanalysis: Anti-tumor necrosis factor alpha therapy and cardiovascular events in rheumatoid arthritis. Arthritis Care Res (Hoboken) 2011; 63: 522-529.
38. Jacobsson LT, Turesson C, Gulfe A, Kapetanovic MC, Petersson IF, Saxne T, et al. Treatment with tumor necrosis factor blockers is associated with a lower incidence of first cardiovascular events in patients with rheumatoid arthritis. J Rheumatol 2005; 32: 1213-1218.
39. Nguyen T, Wu JJ. Relationship between tumor necrosis factoralpha inhibitors and cardiovascular disease in psoriasis: A review. Perm J 2014; 18: 49-54.
40. Clausell N, Molossi S, Sett S, Rabinovitch M. In vivo blockade of tumor necrosis factor-alpha in cholesterol-fed rabbits after cardiac transplant inhibits acute coronary artery neointimal formation. Circulation 1994; 89: 2768-2779.
41. Zhou Z, Lauer MA, Wang K, Forudi F, Zhou X, Song X, et al. Effect of anti-tumor necrosis factor-alpha polyclonal antibody on restenosis after balloon angioplasty in a rabbit atherosclerotic model. Atherosclerosis 2002; 161: 153-159.
42. Branen L, Hovgaard L, Nitulescu M, Bengtsson E, Nilsson J, Jovinge S. Inhibition of tumor necrosis factor-alpha reduces atherosclerosis in apolipoprotein E knockout mice. Arterioscler Thromb Vasc Biol 2004; 24: 2137-2142.
43. Miyazaki Y, Pipek R, Mandarino LJ, DeFronzo RA. Tumor necrosis factor alpha and insulin resistance in obese type 2 diabetic patients. Int J Obes Relat Metab Disord 2003; 27: 88-94.
44. Gupta-Ganguli M, Cox K, Means B, Gerling I, Solomon SS. Does therapy with anti-TNF-alpha improve glucose tolerance and control in patients with type 2 diabetes? Diabetes Care 2011; 34: e121, doi:10.2337/dc10-1334.
45. Popa C, van den Hoogen FHJ, Radstake TRDJ, Netea MG, Eijsbouts AE, Heijer Md, et al. Modulation of lipoprotein plasma concentrations during long-term anti-TNF therapy in patients with active rheumatoid arthritis. Ann Rheum Dis 2007; 66: 1503-1507.
46. Kerekes G, Soltesz P, Der H, Veres K, Szabo Z, Vegvari A, et al. Effects of biologics on vascular function and atherosclerosis associated with rheumatoid arthritis. Ann NY Acad Sci 2009; 1173: 814-821.
47. Sinagra E, Perricone G, Romano C, Cottone M. Heart failure and anti tumor necrosis factor-alpha in systemic chronic inflammatory diseases. Eur J Intern Med 2013; 24: 385-392.
48. Monaco C, Nanchahal J, Taylor P, Feldmann M. Anti-TNF therapy: Past, present and future. Int Immunol 2015; 27: 55-62.
49. Masters SL, Simon A, Aksentijevich I, Kastner DL. Horror autoinflammaticus: The molecular pathophysiology of autoinflammatory disease (*). Annu Rev Immunol 2009; 27: 621-668.
50. Dinarello CA. Interleukin-1 in the pathogenesis and treatment of inflammatory diseases. Blood 2011; 117: 3720-3732.
51. Abramson SB, Amin A. Blocking the effects of IL-1 in rheumatoid arthritis protects bone and cartilage. Rheumatology (Oxford) 2002; 41: 972-980.
52. Kleemann R, Zadelaar S, Kooistra T. Cytokines and atherosclero sis: A comprehensive review of studies in mice. Cardiovasc Res 2008; 79: 360-376.
53. Li X, Deroide N, Mallat Z. The role of the inflammasome in cardiovascular diseases. J Mol Med (Berl) 2014; 92: 307-319.
54. Latz E, Xiao TS, Stutz A. Activation and regulation of the inflammasomes. Nat Rev Immunol 2013; 13: 397-411.
55. Duewell P, Kono H, Rayner KJ, Sirois CM, Vladimer G, Bauernfeind FG, et al. NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals. Nature 2010; 464: 1357-1361.
56. Martinon F, Petrilli V, Mayor A, Tardivel A, Tschopp J. Goutassociated uric acid crystals activate the NALP3 inflammasome. Nature 2006; 440: 237-241.
57. So A, De Smedt T, Revaz S, Tschopp J. A pilot study of IL-1 inhibition by anakinra in acute gout. Arthritis Res Ther 2007; 9: R28.
58. Nidorf SM, Eikelboom JW, Budgeon CA, Thompson PL. Lowdose colchicine for secondary prevention of cardiovascular disease. J Am Coll Cardiol 2013; 61: 404-410.
59. Ikonomidis I, Tzortzis S, Andreadou I, Paraskevaidis I, Katseli C, Katsimbri P, et al. Increased benefit of interleukin-1 inhibition on vascular function, myocardial deformation, and twisting in patients with coronary artery disease and coexisting rheumatoid arthritis. Circ Cardiovasc Imaging 2014; 7: 619-628.
60. Ridker PM, Thuren T, Zalewski A, Libby P. Interleukin-1beta inhibition and the prevention of recurrent cardiovascular events: Rationale and design of the Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS). Am Heart J 2011; 162: 597-605.
61. Ridker PM, Howard CP, Walter V, Everett B, Libby P, Hensen J, et al. Effects of interleukin-1beta inhibition with canakinumab on hemoglobin A1c, lipids, C-reactive protein, interleukin-6, and fibrinogen: A phase IIb randomized, placebo-controlled trial. Circulation 2012; 126: 2739-2748.
62. Hennigan S, Kavanaugh A. Interleukin-6 inhibitors in the treatment of rheumatoid arthritis. Ther Clin Risk Manag 2008; 4: 767-775.
63. Kawashiri SY, Kawakami A, Yamasaki S, Imazato T, Iwamoto N, Fujikawa K, et al. Effects of the anti-interleukin-6 receptor antibody, tocilizumab, on serum lipid levels in patients with rheumatoid arthritis. Rheumatol Int 2011; 31: 451-456.
64. Rao VU, Pavlov A, Klearman M, Musselman D, Giles JT, Bathon JM, et al. An evaluation of risk factors for major adverse cardiovascular events during tocilizumab therapy. Arthritis Rheumatol 2015; 67: 372-380.
65. Ettinger WH, Varma VK, Sorci-Thomas M, Parks JS, Sigmon RC, Smith TK, et al. Cytokines decrease apolipoprotein accumulation in medium from Hep G2 cells. Arterioscler Thromb 1994; 14: 8-13.
66. Huber SA, Sakkinen P, Conze D, Hardin N, Tracy R. Interleukin-6 exacerbates early atherosclerosis in mice. Arterioscler Thromb Vasc Biol 1999; 19: 2364-2367.
67. Scheller J, Garbers C, Rose-John S. Interleukin-6: From basic biology to selective blockade of pro-inflammatory activities. Semin Immunol 2014; 26: 2-12.
68. Koga M, Kai H, Yasukawa H, Yamamoto T, Kawai Y, Kato S, et al. Inhibition of progression and stabilization of plaques by postnatal interferon-gamma function blocking in ApoE-knockout mice. Circ Res 2007; 101: 348-356.
69. Chao CC, Chen SJ, Adamopoulos IE, Davis N, Hong K, Vu A, et al. Anti-IL-17A therapy protects against bone erosion in experimental models of rheumatoid arthritis. Autoimmunity 2011; 44: 243-252.
70. Krueger JG, Fretzin S, Suarez-Farinas M, Haslett PA, Phipps KM, Cameron GS, et al. IL-17A is essential for cell activation and inflammatory gene circuits in subjects with psoriasis. J Allergy Clin Immunol 2012; 130: 145-154.e149, doi:10.1016/j.jaci.2012.04.024.
71. Komiyama Y, Nakae S, Matsuki T, Nambu A, Ishigame H, Kakuta S, et al. IL-17 plays an important role in the development of experimental autoimmune encephalomyelitis. J Immunol 2006; 177: 566-573.
72. Erbel C, Chen L, Bea F, Wangler S, Celik S, Lasitschka F, et al. Inhibition of IL-17A attenuates atherosclerotic lesion development in apoE-deficient mice. J Immunol 2009; 183: 8167-8175.
73. Gao Q, Jiang Y, Ma T, Zhu F, Gao F, Zhang P, et al. A critical function of Th17 proinflammatory cells in the development of atherosclerotic plaque in mice. J Immunol 2010; 185: 5820-5827.
74. Smith E, Prasad KM, Butcher M, Dobrian A, Kolls JK, Ley K, et al. Blockade of interleukin-17A results in reduced atherosclerosis in apolipoprotein E-deficient mice. Circulation 2010; 121: 1746-1755.
75. Gistera A, Robertson AK, Andersson J, Ketelhuth DF, Ovchinnikova O, Nilsson SK, et al. Transforming growth factor-beta signaling in T cells promotes stabilization of atherosclerotic plaques through an interleukin-17-dependent pathway. Sci Transl Med 2013; 5: 196ra100.
76. Hugh J, Van Voorhees AS, Nijhawan RI, Bagel J, Lebwohl M, Blauvelt A, et al. From the Medical Board of the National Psoriasis Foundation: The risk of cardiovascular disease in individuals with psoriasis and the potential impact of current therapies. J Am Acad Dermatol 2014; 70: 168-177.
77. Hauer AD, Uyttenhove C, de Vos P, Stroobant V, Renauld JC, van Berkel TJ, et al. Blockade of interleukin-12 function by protein vaccination attenuates atherosclerosis. Circulation 2005; 112: 1054-1062.
78. Baechler EC, Batliwalla FM, Karypis G, Gaffney PM, Ortmann WA, Espe KJ, et al. Interferon-inducible gene expression signature in peripheral blood cells of patients with severe lupus. Proc Natl Acad Sci USA 2003; 100: 2610-2615.
79. Lee PY, Li Y, Richards HB, Chan FS, Zhuang H, Narain S, et al. Type I interferon as a novel risk factor for endothelial progenitor cell depletion and endothelial dysfunction in systemic lupus erythematosus. Arthritis Rheum 2007; 56: 3759-3769.
80. Goossens P, Gijbels MJ, Zernecke A, Eijgelaar W, Vergouwe MN, van der Made I, et al. Myeloid type I interferon signaling promotes atherosclerosis by stimulating macrophage recruitment to lesions. Cell Metab 2010; 12: 142-153.
81. Lauwerys BR, Ducreux J, Houssiau FA. Type I interferon blockade in systemic lupus erythematosus: Where do we stand? Rheumatology (Oxford) 2014; 53: 1369-1376.
82. Jager A, Kuchroo VK. Effector and regulatory T-cell subsets in autoimmunity and tissue inflammation. Scand J Immunol 2010; 72: 173-184.
83. O’Shea JJ, Kanno Y, Chan AC. In search of magic bullets: The golden age of immunotherapeutics. Cell 2014; 157: 227-240.
84. Haqqi TM, Qu XM, Anthony D, Ma J, Sy MS. Immunization with T cell receptor V beta chain peptides deletes pathogenic T cells and prevents the induction of collagen-induced arthritis in mice. J Clin Invest 1996; 97: 2849-2858.
85. Howell MD, Winters ST, Olee T, Powell HC, Carlo DJ, Brostoff SW. Vaccination against experimental allergic encephalomyelitis with T cell receptor peptides. Science 1989; 246: 668-670.
86. Smolen JS, Landewe R, Breedveld FC, Buch M, Burmester G, Dougados M, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update. Ann Rheum Dis 2014; 73: 492-509.
87. Mathieu S, Couderc M, Glace B, Pereira B, Tournadre A, Dubost JJ, et al. Effects of 6 months of abatacept treatment on aortic stiffness in patients with rheumatoid arthritis. Biologics 2013; 7: 259-264.
88. Ewing MM, Karper JC, Abdul S, de Jong RC, Peters HA, de Vries MR, et al. T-cell co-stimulation by CD28-CD80/86 and its negative regulator CTLA-4 strongly influence accelerated atherosclerosis development. Int J Cardiol 2013; 168: 1965-1974.
89. Vinh A, Chen W, Blinder Y, Weiss D, Taylor WR, Goronzy JJ, et al. Inhibition and genetic ablation of the B7/CD28 T-cell costimulation axis prevents experimental hypertension. Circulation 2010; 122: 2529-2537.
90. Ford ML, Adams AB, Pearson TC. Targeting co-stimulatory pathways: Transplantation and autoimmunity. Nat Rev Nephrol 2014; 10: 14-24.
91. Yazdany J, Davis J. The role of CD40 ligand in systemic lupus erythematosus. Lupus 2004; 13: 377-380.
92. Amirkhosravi A, Amaya M, Desai H, Francis JL. Platelet-CD40 ligand interaction with melanoma cell and monocyte CD40 enhances cellular procoagulant activity. Blood Coagul Fibrinolysis 2002; 13: 505-512.
93. Schonbeck U, Libby P. CD40 signaling and plaque instability. Circ Res 2001; 89: 1092-1103.
94. Henn V, Slupsky JR, Grafe M, Anagnostopoulos I, Forster R, Muller-Berghaus G, et al. CD40 ligand on activated platelets triggers an inflammatory reaction of endothelial cells. Nature 1998; 391: 591-594.
95. Mach F, Schonbeck U, Sukhova GK, Atkinson E, Libby P. Reduction of atherosclerosis in mice by inhibition of CD40 signalling. Nature 1998; 394: 200-203.
96. Lutgens E, Cleutjens KB, Heeneman S, Koteliansky VE, Burkly LC, Daemen MJ. Both early and delayed anti-CD40L antibody treatment induces a stable plaque phenotype. Proc Natl Acad Sci USA 2000; 97: 7464-7469.
97. Wang X, Ria M, Kelmenson PM, Eriksson P, Higgins DC, Samnegard A, et al. Positional identification of TNFSF4, encoding OX40 ligand, as a gene that influences atherosclerosis susceptibility. Nat Genet 2005; 37: 365-372.
98. van Wanrooij EJ, van Puijvelde GH, de Vos P, Yagita H, van Berkel TJ, Kuiper J. Interruption of the Tnfrsf4/Tnfsf4 (OX40/ OX40L) pathway attenuates atherogenesis in low-density lipoprotein receptor-deficient mice. Arterioscler Thromb Vasc Biol 2007; 27: 204-210.
99. Foell J, Strahotin S, O’Neil SP, McCausland MM, Suwyn C, Haber M, et al. CD137 costimulatory T cell receptor engagement reverses acute disease in lupus-prone NZB×NZW F1 mice. J Clin Invest 2003; 111: 1505-1518.
100. Sun Y, Chen HM, Subudhi SK, Chen J, Koka R, Chen L, et al. Costimulatory molecule-targeted antibody therapy of a spontaneous autoimmune disease. Nat Med 2002; 8: 1405-1413.
101. Olofsson PS, Soderstrom LA, Wagsater D, Sheikine Y, Ocaya P, Lang F, et al. CD137 is expressed in human atherosclerosis and promotes development of plaque inflammation in hypercholesterolemic mice. Circulation 2008; 117: 1292-1301.
102. Suntharalingam G, Perry MR, Ward S, Brett SJ, Castello-Cortes A, Brunner MD, et al. Cytokine storm in a Phase 1 trial of the anti- CD28 monoclonal antibody TGN1412. N Engl J Med 2006; 355: 1018-1028.
103. Sakaguchi S, Yamaguchi T, Nomura T, Ono M. Regulatory T cells and immune tolerance. Cell 2008; 133: 775-787.
104. Wellcome Trust Case Control Consortium. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 2007; 447: 661-678.
105. Foks AC, Frodermann V, ter Borg M, Habets KLL, Bot I, Zhao Y, et al. Differential effects of regulatory T cells on the initiation and regression of atherosclerosis. Atherosclerosis 2011; 218: 53-60.
106. Boyman O, Sprent J. The role of interleukin-2 during homeostasis and activation of the immune system. Nat Rev Immunol 2012; 12: 180-190.
107. Saadoun D, Rosenzwajg M, Joly F, Six A, Carrat F, Thibault V, et al. Regulatory T-cell responses to low-dose interleukin-2 in HCVinduced vasculitis. N Engl J Med 2011; 365: 2067-2077.
108. Hippen KL, Riley JL, June CH, Blazar BR. Clinical perspectives for regulatory T cells in transplantation tolerance. Semin Immunol 2011; 23: 462-468.
109. Ait-Oufella H, Salomon BL, Potteaux S, Robertson AK, Gourdy P, Zoll J, et al. Natural regulatory T cells control the development of atherosclerosis in mice. Nat Med 2006; 12: 178-180.
110. Robertson AK, Rudling M, Zhou X, Gorelik L, Flavell RA, Hansson GK. Disruption of TGF-beta signaling in T cells accelerates atherosclerosis. J Clin Invest 2003; 112: 1342-1350.
111. Mallat Z, Gojova A, Marchiol-Fournigault C, Esposito B, Kamate C, Merval R, et al. Inhibition of transforming growth factor-beta signaling accelerates atherosclerosis and induces an unstable plaque phenotype in mice. Circ Res 2001; 89: 930-934.
112. Klingenberg R, Gerdes N, Badeau RM, Gisterå A, Strodthoff D, Ketelhuth DF, et al. Depletion of FOXP3+ regulatory T cells promotes hypercholesterolemia and atherosclerosis. J Clin Invest 2013; 123: 1323-1334.
113. Cheng X, Yu X, Ding YJ, Fu QQ, Xie JJ, Tang TT, et al. The Th17/ Treg imbalance in patients with acute coronary syndrome. Clin Immunol 2008; 127: 89-97.
114. Kofler S, Sisic Z, Shvets N, Lohse P, Weis M. Expression of circulatory dendritic cells and regulatory T-cells in patients with different subsets of coronary artery disease. J Cardiovasc Pharmacol 2011; 57: 542-549.
115. Potekhina AV, Provatorov SI, Sokolov VO, Pylaeva EA, Masenko VP, Noeva EA, et al. CD4(+)CD25(high)CD127(low) regulatory T cells in patients with stable angina and their dynamics after intracoronary sirolimus-eluting stent implantation. Hum Immunol 2011; 72: 553-557.
116. Emoto T, Sasaki N, Yamashita T, Kasahara K, Yodoi K, Sasaki Y, et al. Regulatory/effector T-cell ratio is reduced in coronary artery disease. Circ J 2014; 78: 2935-2941.
117. Meng X, Zhang K, Li J, Dong M, Yang J, An G, et al. Statins induce the accumulation of regulatory T cells in atherosclerotic plaque. Mol Med 2012; 18: 598-605.
118. Zhang D, Wang S, Guan Y, Wang L, Xie W, Li N, et al. Effect of oral atorvastatin on CD4+CD25+ regulatory T cells, FoxP3 expression, and prognosis in patients with ST-segment elevated myocardial infarction before primary percutaneous coronary intervention. J Cardiovasc Pharmacol 2011; 57: 536-541.
119. Mausner-Fainberg K, Luboshits G, Mor A, Maysel-Auslender S, Rubinstein A, Keren G, et al. The effect of HMG-CoA reductase inhibitors on naturally occurring CD4+CD25+ T cells. Atherosclerosis 2008; 197: 829-839.
120. Liu Z, Zhao Y, Wei F, Ye L, Lu F, Zhang H, et al. Treatment with telmisartan/rosuvastatin combination has a beneficial synergistic effect on ameliorating Th17/Treg functional imbalance in hypertensive patients with carotid atherosclerosis. Atherosclerosis 2014; 233: 291-299.
121. Mallat Z, Gojova A, Brun V, Esposito B, Fournier N, Cottrez F, et al. Induction of a regulatory T cell type 1 response reduces the development of atherosclerosis in apolipoprotein E-knockout mice. Circulation 2003; 108: 1232-1237.
122. Steffens S, Burger F, Pelli G, Dean Y, Elson G, Kosco-Vilbois M, et al. Short-term treatment with anti-CD3 antibody reduces the development and progression of atherosclerosis in mice. Circulation 2006; 114: 1977-1984.
123. Groyer E, Nicoletti A, Ait-Oufella H, Khallou-Laschet J, Varthaman A, Gaston AT, et al. Atheroprotective effect of CD31 receptor globulin through enrichment of circulating regulatory T-cells. J Am Coll Cardiol 2007; 50: 344-350.
124. Takeda M, Yamashita T, Sasaki N, Nakajima K, Kita T, Shinohara M, et al. Oral administration of an active form of vitamin D3 (calcitriol) decreases atherosclerosis in mice by inducing regulatory T cells and immature dendritic cells with tolerogenic functions. Arterioscler Thromb Vasc Biol 2010; 30: 2495-2503.
125. Klingenberg R, Lebens M, Hermansson A, Fredrikson GN, Strodthoff D, Rudling M, et al. Intranasal immunization with an apolipoprotein B-100 fusion protein induces antigen-specific regulatory T cells and reduces atherosclerosis. Arterioscler Thromb Vasc Biol 2010; 30: 946-952.
126. Wigren M, Kolbus D, Duner P, Ljungcrantz I, Soderberg I, Bjorkbacka H, et al. Evidence for a role of regulatory T cells in mediating the atheroprotective effect of apolipoprotein B peptide vaccine. J Intern Med 2011; 269: 546-556.
127. Hermansson A, Johansson DK, Ketelhuth DF, Andersson J, Zhou X, Hansson GK. Immunotherapy with tolerogenic apolipoprotein B-100-loaded dendritic cells attenuates atherosclerosis in hypercholesterolemic mice. Circulation 2011; 123: 1083-1091.
128. van Puijvelde GHM, Hauer AD, de Vos P, van den Heuvel R, van Herwijnen MJC, van der Zee R, et al. Induction of oral tolerance to oxidized low-density lipoprotein ameliorates atherosclerosis. Circulation 2006; 114: 1968-1976.
129. Maron R, Sukhova G, Faria AM, Hoffmann E, Mach F, Libby P, et al. Mucosal administration of heat shock protein-65 decreases atherosclerosis and inflammation in aortic arch of low-density lipoprotein receptor-deficient mice. Circulation 2002; 106: 1708-1715.
130. Klingenberg R, Ketelhuth DF, Strodthoff D, Gregori S, Hansson GK. Subcutaneous immunization with heat shock protein-65 reduces atherosclerosis in Apoe(–/–) mice. Immunobiology 2012; 217: 540-547.
131. George J, Yacov N, Breitbart E, Bangio L, Shaish A, Gilburd B, et al. Suppression of early atherosclerosis in LDL-receptor deficient mice by oral tolerance with beta 2-glycoprotein I. Cardiovasc Res 2004; 62: 603-609.
132. Dorner T, Giesecke C, Lipsky PE. Mechanisms of B cell autoimmunity in SLE. Arthritis Res Ther 2011; 13: 243.
133. Mauri C, Bosma A. Immune regulatory function of B cells. Annu Rev Immunol 2012; 30: 221-241.
134. Pescovitz MD, Greenbaum CJ, Krause-Steinrauf H, Becker DJ, Gitelman SE, Goland R, et al. Rituximab, B-lymphocyte depletion, and preservation of beta-cell function. N Engl J Med 2009; 361: 2143-2152.
135. Tony HP, Burmester G, Schulze-Koops H, Grunke M, Henes J, Kotter I, et al. Safety and clinical outcomes of rituximab therapy in patients with different autoimmune diseases: Experience from a national registry (GRAID). Arthritis Res Ther 2011; 13: R75.
136. Hsue PY, Scherzer R, Grunfeld C, Imboden J, Wu Y, Del Puerto G, et al. Depletion of B-cells with rituximab improves endothelial function and reduces inflammation among individuals with rheumatoid arthritis. J Am Heart Assoc 2014; 3: e001267, doi:10.1161/JAHA.114.001267.
137. Kerekes G, Soltesz P, Der H, Veres K, Szabo Z, Vegvari A, et al. Effects of rituximab treatment on endothelial dysfunction, carotid atherosclerosis, and lipid profile in rheumatoid arthritis. Clin Rheumatol 2009; 28: 705-710.
138. Rubbert-Roth A, Tak PP, Zerbini C, Tremblay JL, Carreno L, Armstrong G, et al. Efficacy and safety of various repeat treatment dosing regimens of rituximab in patients with active rheumatoid arthritis: Results of a Phase III randomized study (MIRROR). Rheumatology (Oxford) 2010; 49: 1683-1693.
139. Das S, Fernandez Matilla M, Dass S, Buch MH, Rawstron AC, Vital EM, et al. Statins do not influence clinical response and B cell depletion after rituximab treatment in rheumatoid arthritis. Ann Rheum Dis 2013; 72: 463-464.
140. Arts EE, Jansen TL, Den Broeder A, Vonkeman HE, Dutmer E, Van de Laar MA, et al. Statins inhibit the antirheumatic effects of rituximab in rheumatoid arthritis: Results from the Dutch Rheumatoid Arthritis Monitoring (DREAM) registry. Ann Rheum Dis 2011; 70: 877-878.
141. Caligiuri G, Nicoletti A, Poirier B, Hansson GK. Protective immunity against atherosclerosis carried by B cells of hypercholesterolemic mice. J Clin Invest 2002; 109: 745-753.
142. Major AS, Fazio S, Linton MF. B-lymphocyte deficiency increases atherosclerosis in LDL receptor-null mice. Arterioscler Thromb Vasc Biol 2002; 22: 1892-1898.
143. Kyaw T, Tay C, Krishnamurthi S, Kanellakis P, Agrotis A, Tipping P, et al. B1a B lymphocytes are atheroprotective by secreting natural IgM that increases IgM deposits and reduces necrotic cores in atherosclerotic lesions. Circ Res 2011; 109: 830-840.
144. Kyaw T, Tipping P, Toh BH, Bobik A. Current understanding of the role of B cell subsets and intimal and adventitial B cells in atherosclerosis. Curr Opin Lipidol 2011; 22: 373-379.
145. Sage AP, Tsiantoulas D, Baker L, Harrison J, Masters L, Murphy D, et al. BAFF receptor deficiency reduces the development of atherosclerosis in mice: Brief report. Arterioscler Thromb Vasc Biol 2012; 32: 1573-1576.
146. Hahn BH. Belimumab for systemic lupus erythematosus. N Engl J Med 2013; 368: 1528-1535.
147. Ketelhuth DF, Tonini GC, Carvalho MD, Ramos RF, Boschcov P, Gidlund M. Autoantibody response to chromatographic fractions from oxidized LDL in unstable angina patients and healthy controls. Scand J Immunol 2008; 68: 456-462.
148. Palinski W, Yla-Herttuala S, Rosenfeld ME, Butler SW, Socher SA, Parthasarathy S, et al. Antisera and monoclonal antibodies specific for epitopes generated during oxidative modification of low density lipoprotein. Arteriosclerosis 1990; 10: 325-335.
149. Palinski W, Horkko S, Miller E, Steinbrecher UP, Powell HC, Curtiss LK, et al. Cloning of monoclonal autoantibodies to epitopes of oxidized lipoproteins from apolipoprotein E-deficient mice: Demonstration of epitopes of oxidized low density lipoprotein in human plasma. J Clin Invest 1996; 98: 800-814.
150. Tsimikas S. Oxidized low-density lipoprotein biomarkers in atherosclerosis. Curr Atheroscler Rep 2006; 8: 55-61.
151. Fredrikson GN, Hedblad B, Berglund G, Alm R, Ares M, Cercek B, et al. Identification of immune responses against aldehydemodified peptide sequences in apoB associated with cardiovascular disease. Arterioscler Thromb Vasc Biol 2003; 23: 872-878.
152. Yla-Herttuala S, Palinski W, Butler SW, Picard S, Steinberg D, Witztum JL. Rabbit and human atherosclerotic lesions contain IgG that recognizes epitopes of oxidized LDL. Arterioscler Thromb 1994; 14: 32-40.
153. Hansson GK, Bondjers G, Bylock A, Hjalmarsson L. Ultrastructural studies on the localization of IgG in the aortic endothelium and subendothelial intima of atherosclerotic and nonatherosclerotic rabbits. Exp Mol Pathol 1980; 33: 302-315.
154. de Jager SC, Kuiper J. Vaccination strategies in atherosclerosis. Thromb Haemost 2011; 106: 796-803.
155. Hansson GK, Nilsson J. Vaccination against atherosclerosis?: Induction of atheroprotective immunity. Semin Immunopathol 2009; 31: 95-101.
156. Shah PK, Chyu K, Dimayuga PC, Nilsson J. Vaccine for atherosclerosis. J Am Coll Cardiol 2014; 64: 2779-2791.
157. Faria-Neto JR, Chyu KY, Li X, Dimayuga PC, Ferreira C, Yano J, et al. Passive immunization with monoclonal IgM antibodies against phosphorylcholine reduces accelerated vein graft atherosclerosis in apolipoprotein E-null mice. Atherosclerosis 2006; 189: 83-90.
158. Schiopu A, Bengtsson J, Soderberg I, Janciauskiene S, Lindgren S, Ares MP, et al. Recombinant human antibodies against aldehydemodified apolipoprotein B-100 peptide sequences inhibit atherosclerosis. Circulation 2004; 110: 2047-2052.