Top

Published in:

Open Access 01-12-2013 | Review

Immunity, atherosclerosis and cardiovascular disease

Author: Johan Frostegård

Published in: BMC Medicine | Issue 1/2013

Abstract

Atherosclerosis, the major cause of cardiovascular disease (CVD), is a chronic inflammatory condition with immune competent cells in lesions producing mainly pro-inflammatory cytokines. Dead cells and oxidized forms of low density lipoproteins (oxLDL) are abundant. The major direct cause of CVD appears to be rupture of atherosclerotic plaques. oxLDL has proinflammatory and immune-stimulatory properties, causes cell death at higher concentrations and contains inflammatory phospholipids with phosphorylcholine (PC) as an interesting epitope. Antibodies against PC (anti-PC) may be atheroprotective, one mechanism being anti-inflammatory. Bacteria and virus have been discussed, but it has been difficult to find direct evidence, and antibiotic trials have not been successful. Heat shock proteins could be one major target for atherogenic immune reactions. More direct causes of plaque rupture include pro-inflammatory cytokines, chemokines, and lipid mediators. To prove that inflammation is a cause of atherosclerosis and CVD, clinical studies with anti-inflammatory and/or immune-modulatory treatment are needed. The potential causes of immune reactions and inflammation in atherosclerosis and how inflammation can be targeted therapeutically to provide novel treatments for CVD are reviewed.

Available only for authorised users

Gimbrone MA, Topper JN, Nagel T, Anderson KR, Garcia-Cardena G: Endothelial dysfunction, hemodynamic forces, and atherogenesis. Ann N Y Acad Sci. 2000, 902: 230-239. discussion 239–240PubMed

Campbell KA, Lipinski MJ, Doran AC, Skaflen MD, Fuster V, McNamara CA: Lymphocytes and the adventitial immune response in atherosclerosis. Circ Res. 2012, 110: 889-900.PubMedPubMedCentral

Frostegard J, Ulfgren AK, Nyberg P, Hedin U, Swedenborg J, Andersson U, Hansson GK: Cytokine expression in advanced human atherosclerotic plaques: dominance of pro-inflammatory (Th1) and macrophage-stimulating cytokines. Atherosclerosis. 1999, 145: 33-43.PubMed

Libby P, Ridker PM, Hansson GK: Progress and challenges in translating the biology of atherosclerosis. Nature. 2011, 473: 317-325.PubMed

Camejo G, Lalaguna F, Lopez F, Starosta R: Characterization and properties of a lipoprotein-complexing proteoglycan from human aorta. Atherosclerosis. 1980, 35: 307-320.PubMed

Tabas I, Williams KJ, Boren J: Subendothelial lipoprotein retention as the initiating process in atherosclerosis: update and therapeutic implications. Circulation. 2007, 116: 1832-1844.PubMed

Frostegard J, Nilsson J, Haegerstrand A, Hamsten A, Wigzell H, Gidlund M: Oxidized low density lipoprotein induces differentiation and adhesion of human monocytes and the monocytic cell line U937. Proc Natl Acad Sci USA. 1990, 87: 904-908.PubMedPubMedCentral

Frostegard J, Wu R, Giscombe R, Holm G, Lefvert AK, Nilsson J: Induction of T-cell activation by oxidized low density lipoprotein. Arterioscler Thromb. 1992, 12: 461-467.PubMed

Berliner JA, Territo MC, Sevanian A, Ramin S, Kim JA, Bamshad B, Esterson M, Fogelman AM: Minimally modified low density lipoprotein stimulates monocyte endothelial interactions. J Clin Invest. 1990, 85: 1260-1266.PubMedPubMedCentral

10.

Elinder LS, Dumitrescu A, Larsson P, Hedin U, Frostegard J, Claesson HE: Expression of phospholipase A2 isoforms in human normal and atherosclerotic arterial wall. Arterioscler Thromb Vasc Biol. 1997, 17: 2257-2263.PubMed

11.

Atout R, Karabina SA, Dollet S, Carreras M, Payre C, Andre P, Lambeau G, Lotteau V, Ninio E, Perrin-Cocon L: Human group X secreted phospholipase A2 induces dendritic cell maturation through lipoprotein-dependent and -independent mechanisms. Atherosclerosis. 2012, 222: 367-374.PubMed

12.

Huang YH, Schafer-Elinder L, Wu R, Claesson HE, Frostegard J: Lysophosphatidylcholine (LPC) induces proinflammatory cytokines by a platelet-activating factor (PAF) receptor-dependent mechanism. Clin Exp Immunol. 1999, 116: 326-331.PubMedPubMedCentral

13.

Goncalves I, Edsfeldt A, Ko NY, Grufman H, Berg K, Bjorkbacka H, Nitulescu M, Persson A, Nilsson M, Prehn C, Adamski J, Nilsson J: Evidence supporting a key role of Lp-PLA2-generated lysophosphatidylcholine in human atherosclerotic plaque inflammation. Arterioscler Thromb Vasc Biol. 2012, 32: 1505-1512.PubMed

14.

Frostegard J, Huang YH, Ronnelid J, Schafer-Elinder L: Platelet-activating factor and oxidized LDL induce immune activation by a common mechanism. Arterioscler Thromb Vasc Biol. 1997, 17: 963-968.PubMed

15.

Watson AD, Leitinger N, Navab M, Faull KF, Horkko S, Witztum JL, Palinski W, Schwenke D, Salomon RG, Sha W, Subbanagounder G, Fogelman AM, Berliner JA: Structural identification by mass spectrometry of oxidized phospholipids in minimally oxidized low density lipoprotein that induce monocyte/endothelial interactions and evidence for their presence in vivo. J Biol Chem. 1997, 272: 13597-13607.PubMed

16.

Greig FH, Kennedy S, Spickett CM: Physiological effects of oxidized phospholipids and their cellular signaling mechanisms in inflammation. Free Radic Biol Med. 2012, 52: 266-280.PubMed

17.

Miller YI, Choi SH, Wiesner P, Fang L, Harkewicz R, Hartvigsen K, Boullier A, Gonen A, Diehl CJ, Que X, Montano E, Shaw PX, Tsimikas S, Binder CJ, Witztum JL: Oxidation-specific epitopes are danger-associated molecular patterns recognized by pattern recognition receptors of innate immunity. Circ Res. 2011, 108: 235-248.PubMedPubMedCentral

18.

Yusuf S, Hawken S, Ounpuu S, Dans T, Avezum A, Lanas F, McQueen M, Budaj A, Pais P, Varigos J, Lisheng L: Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case–control study. Lancet. 2004, 364: 937-952.PubMed

19.

Yanbaeva DG, Dentener MA, Creutzberg EC, Wesseling G, Wouters EF: Systemic effects of smoking. Chest. 2007, 131: 1557-1566.PubMed

20.

Morrow JD, Frei B, Longmire AW, Gaziano JM, Lynch SM, Shyr Y, Strauss WE, Oates JA, Roberts LJ: Increase in circulating products of lipid peroxidation (F2-isoprostanes) in smokers smoking as a cause of oxidative damage. N Engl J Med. 1995, 332: 1198-1203.PubMed

21.

Penn A, Snyder CA: Inhalation of sidestream cigarette smoke accelerates development of arteriosclerotic plaques. Circulation. 1993, 88: 1820-1825.PubMed

22.

Zhu BQ, Sun YP, Sievers RE, Isenberg WM, Glantz SA, Parmley WW: Passive smoking increases experimental atherosclerosis in cholesterol-fed rabbits. J Am Coll Cardiol. 1993, 21: 225-232.PubMed

23.

Gairola CG, Drawdy ML, Block AE, Daugherty A: Sidestream cigarette smoke accelerates atherogenesis in apolipoprotein E−/− mice. Atherosclerosis. 2001, 156: 49-55.PubMed

24.

Kunitomo M, Yamaguchi Y, Kagota S, Yoshikawa N, Nakamura K, Shinozuka K: Biochemical evidence of atherosclerosis progression mediated by increased oxidative stress in apolipoprotein E-deficient spontaneously hyperlipidemic mice exposed to chronic cigarette smoke. J Pharmacol Sci. 2009, 110: 354-361.PubMed

25.

Frostegard J: Atherosclerosis in patients with autoimmune disorders. Arterioscler Thromb Vasc Biol. 2005, 25: 1776-1785.PubMed

26.

Dimitriadis E, Griffin M, Owens D, Johnson A, Collins P, Tomkin GH: Oxidation of low-density lipoprotein in NIDDM: its relationship to fatty acid composition. Diabetologia. 1995, 38: 1300-1306.PubMed

27.

Beckman JA, Goldfine AB, Gordon MB, Creager MA: Ascorbate restores endothelium-dependent vasodilation impaired by acute hyperglycemia in humans. Circulation. 2001, 103: 1618-1623.PubMed

28.

Nishikawa T, Edelstein D, Du XL, Yamagishi S, Matsumura T, Kaneda Y, Yorek MA, Beebe D, Oates PJ, Hammes HP, Giardino I, Brownlee M: Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage. Nature. 2000, 404: 787-790.PubMed

29.

Laursen JB, Somers M, Kurz S, McCann L, Warnholtz A, Freeman BA, Tarpey M, Fukai T, Harrison DG: Endothelial regulation of vasomotion in apoE-deficient mice: implications for interactions between peroxynitrite and tetrahydrobiopterin. Circulation. 2001, 103: 1282-1288.PubMed

30.

Iyer SS, Pulskens WP, Sadler JJ, Butter LM, Teske GJ, Ulland TK, Eisenbarth SC, Florquin S, Flavell RA, Leemans JC, Sutterwala FS: Necrotic cells trigger a sterile inflammatory response through the Nlrp3 inflammasome. Proc Natl Acad Sci USA. 2009, 106: 20388-20393.PubMedPubMedCentral

31.

Zheng Y, Gardner SE, Clarke MC: Cell death, damage-associated molecular patterns, and sterile inflammation in cardiovascular disease. Arterioscler Thromb Vasc Biol. 2011, 31: 2781-2786.PubMed

32.

Anania C, Gustafsson T, Hua X, Su J, Vikstrom M, De Faire U, Heimburger M, Jogestrand T, Frostegard J: Increased prevalence of vulnerable atherosclerotic plaques and low levels of natural IgM antibodies against phosphorylcholine in patients with systemic lupus erythematosus. Arthritis Res Ther. 2010, 12: R214.PubMedPubMedCentral

33.

Cederholm A, Svenungsson E, Jensen-Urstad K, Trollmo C, Ulfgren AK, Swedenborg J, Fei GZ, Frostegard J: Decreased binding of annexin v to endothelial cells: a potential mechanism in atherothrombosis of patients with systemic lupus erythematosus. Arterioscler Thromb Vasc Biol. 2005, 25: 198-203.PubMed

34.

Paradies G, Petrosillo G, Paradies V, Ruggiero FM: Oxidative stress, mitochondrial bioenergetics, and cardiolipin in aging. Free Radic Biol Med. 2010, 48: 1286-1295.PubMed

35.

Martin W, Hoffmeister M, Rotte C, Henze K: An overview of endosymbiotic models for the origins of eukaryotes, their ATP-producing organelles (mitochondria and hydrogenosomes), and their heterotrophic lifestyle. Biol Chem. 2001, 382: 1521-1539.PubMed

36.

Su J, Hua X, Vikstrom M, Leander K, Gigante B, Hellenius ML, De Faire U, Frostegard J: Low levels of IgM antibodies to oxidized cardiolipin increase and high levels decrease risk of cardiovascular disease among 60-year olds: a prospective study. BMC Cardiovasc Disord. 2013, 13: 1.PubMedPubMedCentral

37.

Frostegard J: Low level natural antibodies against phosphorylcholine: a novel risk marker and potential mechanism in atherosclerosis and cardiovascular disease. Clin Immunol. 2010, 134: 47-54.PubMed

38.

Binder CJ, Horkko S, Dewan A, Chang MK, Kieu EP, Goodyear CS, Shaw PX, Palinski W, Witztum JL, Silverman GJ: Pneumococcal vaccination decreases atherosclerotic lesion formation: molecular mimicry between Streptococcus pneumoniae and oxidized LDL. Nat Med. 2003, 9: 736-743.PubMed

39.

Faria-Neto JR, Chyu KY, Li X, Dimayuga PC, Ferreira C, Yano J, Cercek B, Shah PK: Passive immunization with monoclonal IgM antibodies against phosphorylcholine reduces accelerated vein graft atherosclerosis in apolipoprotein E-null mice. Atherosclerosis. 2006, 189: 83-90.PubMed

40.

Caligiuri G, Khallou-Laschet J, Vandaele M, Gaston AT, Delignat S, Mandet C, Kohler HV, Kaveri SV, Nicoletti A: Phosphorylcholine-targeting immunization reduces atherosclerosis. J Am Coll Cardiol. 2007, 50: 540-546.PubMed

41.

Su J, Georgiades A, Wu R, Thulin T, De Faire U, Frostegard J: Antibodies of IgM subclass to phosphorylcholine and oxidized LDL are protective factors for atherosclerosis in patients with hypertension. Atherosclerosis. 2006, 188: 160-166.PubMed

42.

Su J, Hua X, Concha H, Svenungsson E, Cederholm A, Frostegard J: Natural antibodies against phosphorylcholine as potential protective factors in SLE. Rheumatology (Oxford). 2008, 47: 1144-1150.

43.

De Faire U, Su J, Hua X, Frostegard A, Halldin M, Hellenius ML, Wikstrom M, Dahlbom I, Gronlund H, Frostegard J: Low levels of IgM antibodies to phosphorylcholine predict cardiovascular disease in 60-year old men: effects on uptake of oxidized LDL in macrophages as a potential mechanism. J Autoimmun. 2010, 34: 73-79.PubMed

44.

Fiskesund R, Su J, Viksröm M, Faire U, Frostegård J: Phosphorylcholine antibodies of the Group I idiotype inhibit cell death and, at high levels, are strong protection markers for atherosclerosis development, particularly when combined with other antibodies against modified LDL. Results Immunol. 2012, 2: 13-18.PubMedPubMedCentral

45.

Gronwall C, Vas J, Silverman GJ: Protective roles of natural IgM antibodies. Front Immunol. 2012, 3: 66.PubMedPubMedCentral

46.

Agmon-Levin N, Bat-sheva PK, Barzilai O, Ram M, Lindeberg S, Frostegard J, Shoenfeld Y: Antitreponemal antibodies leading to autoantibody production and protection from atherosclerosis in Kitavans from Papua New Guinea. Ann N Y Acad Sci. 2009, 1173: 675-682.PubMed

47.

Elkan AC, Sjoberg B, Kolsrud B, Ringertz B, Hafstrom I, Frostegard J: Gluten-free vegan diet induces decreased LDL and oxidized LDL levels and raised atheroprotective natural antibodies against phosphorylcholine in patients with rheumatoid arthritis: a randomized study. Arthritis Res Ther. 2008, 10: R34.PubMedPubMedCentral

48.

Rahman I, Atout R, Pedersen NL, De Faire U, Frostegard J, Ninio E, Bennet AM, Magnusson PK: Genetic and environmental regulation of inflammatory CVD biomarkers Lp-PLA2 and IgM anti-PC. Atherosclerosis. 2011, 218: 117-122.PubMed

49.

Rossmann A, Henderson B, Heidecker B, Seiler R, Fraedrich G, Singh M, Parson W, Keller M, Grubeck-Loebenstein B, Wick G: T-cells from advanced atherosclerotic lesions recognize hHSP60 and have a restricted T-cell receptor repertoire. Exp Gerontol. 2008, 43: 229-237.PubMed

50.

Knoflach M, Kiechl S, Mayrl B, Kind M, Gaston JS, van der Zee R, Faggionato A, Mayr A, Willeit J, Wick G: T-cell reactivity against HSP60 relates to early but not advanced atherosclerosis. Atherosclerosis. 2007, 195: 333-338.PubMed

51.

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

52.

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

53.

Murshid A, Gong J, Calderwood SK: The role of heat shock proteins in antigen cross presentation. Front Immunol. 2012, 3: 63.PubMedPubMedCentral

54.

Tamura Y, Torigoe T, Kukita K, Saito K, Okuya K, Kutomi G, Hirata K, Sato N: Heat-shock proteins as endogenous ligands building a bridge between innate and adaptive immunity. Immunotherapy. 2012, 4: 841-852.PubMed

55.

Ross R: Atherosclerosis–an inflammatory disease. N Engl J Med. 1999, 340: 115-126.PubMed

56.

Frostegard J, Kjellman B, Gidlund M, Andersson B, Jindal S, Kiessling R: Induction of heat shock protein in monocytic cells by oxidized low density lipoprotein. Atherosclerosis. 1996, 121: 93-103.PubMed

57.

Frostegard J, Lemne C, Andersson B, van der Zee R, Kiessling R, De Faire U: Association of serum antibodies to heat-shock protein 65 with borderline hypertension. Hypertension. 1997, 29: 40-44.PubMed

58.

Pockley AG, Georgiades A, Thulin T, De Faire U, Frostegard J: Serum heat shock protein 70 levels predict the development of atherosclerosis in subjects with established hypertension. Hypertension. 2003, 42: 235-238.PubMed

59.

Rosenfeld ME, Campbell LA: Pathogens and atherosclerosis: update on the potential contribution of multiple infectious organisms to the pathogenesis of atherosclerosis. Thromb Haemost. 2011, 106: 858-867.PubMed

60.

Shor A, Kuo CC, Patton DL: Detection of Chlamydia pneumoniae in coronary arterial fatty streaks and atheromatous plaques. S Afr Med J. 1992, 82: 158-161.PubMed

61.

Saikku P, Leinonen M, Mattila K, Ekman MR, Nieminen MS, Makela PH, Huttunen JK, Valtonen V: Serological evidence of an association of a novel Chlamydia, TWAR, with chronic coronary heart disease and acute myocardial infarction. Lancet. 1988, 2: 983-986.PubMed

62.

Puolakkainen M, Kuo CC, Shor A, Wang SP, Grayston JT, Campbell LA: Serological response to Chlamydia pneumoniae in adults with coronary arterial fatty streaks and fibrolipid plaques. J Clin Microbiol. 1993, 31: 2212-2214.PubMedPubMedCentral

63.

Saikku P, Leinonen M, Tenkanen L, Linnanmaki E, Ekman MR, Manninen V, Manttari M, Frick MH, Huttunen JK: Chronic Chlamydia pneumoniae infection as a risk factor for coronary heart disease in the Helsinki Heart Study. Ann Intern Med. 1992, 116: 273-278.PubMed

64.

O’Connor CM, Dunne MW, Pfeffer MA, Muhlestein JB, Yao L, Gupta S, Benner RJ, Fisher MR, Cook TD: Azithromycin for the secondary prevention of coronary heart disease events: the WIZARD study: a randomized controlled trial. JAMA. 2003, 290: 1459-1466.PubMed

65.

Grayston JT, Kronmal RA, Jackson LA, Parisi AF, Muhlestein JB, Cohen JD, Rogers WJ, Crouse JR, Borrowdale SL, Schron E, Knirsch C: Azithromycin for the secondary prevention of coronary events. N Engl J Med. 2005, 352: 1637-1645.PubMed

66.

Cannon CP, Braunwald E, McCabe CH, Grayston JT, Muhlestein B, Giugliano RP, Cairns R, Skene AM: Antibiotic treatment of Chlamydia pneumoniae after acute coronary syndrome. N Engl J Med. 2005, 352: 1646-1654.PubMed

67.

Lockhart PB, Bolger AF, Papapanou PN, Osinbowale O, Trevisan M, Levison ME, Taubert KA, Newburger JW, Gornik HL, Gewitz MH, Wilson WR, Smith SC, Baddour LM: American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee of the Council on Cardiovascular Disease in the Young, Council on Epidemiology and Prevention, Council on Peripheral Vascular Disease, and Council on Clinical Cardiology: Periodontal disease and atherosclerotic vascular disease: does the evidence support an independent association?: a scientific statement from the American Heart Association. Circulation. 2012, 125: 2520-2544.PubMed

68.

Fateh-Moghadam S, Bocksch W, Wessely R, Jager G, Hetzer R, Gawaz M: Cytomegalovirus infection status predicts progression of heart-transplant vasculopathy. Transplantation. 2003, 76: 1470-1474.PubMed

69.

Melnick JL, Hu C, Burek J, Adam E, DeBakey ME: Cytomegalovirus DNA in arterial walls of patients with atherosclerosis. J Med Virol. 1994, 42: 170-174.PubMed

70.

Streblow DN, Soderberg-Naucler C, Vieira J, Smith P, Wakabayashi E, Ruchti F, Mattison K, Altschuler Y, Nelson JA: The human cytomegalovirus chemokine receptor US28 mediates vascular smooth muscle cell migration. Cell. 1999, 99: 511-520.PubMed

71.

Mach F, Sukhova GK, Michetti M, Libby P, Michetti P: Influence of Helicobacter pylori infection during atherogenesis in vivo in mice. Circ Res. 2002, 90: E1-E4.PubMed

72.

Stone AF, Mendall MA, Kaski JC, Edger TM, Risley P, Poloniecki J, Camm AJ, Northfield TC: Effect of treatment for Chlamydia pneumoniae and Helicobacter pylori on markers of inflammation and cardiac events in patients with acute coronary syndromes: South Thames Trial of Antibiotics in Myocardial Infarction and Unstable Angina (STAMINA). Circulation. 2002, 106: 1219-1223.PubMed

73.

Volzke H, Wolff B, Ludemann J, Guertler L, Kramer A, John U, Felix SB: Seropositivity for anti-Borrelia IgG antibody is independently associated with carotid atherosclerosis. Atherosclerosis. 2006, 184: 108-112.PubMed

74.

Koren O, Spor A, Felin J, Fak F, Stombaugh J, Tremaroli V, Behre CJ, Knight R, Fagerberg B, Ley RE, Backhed F: Human oral, gut, and plaque microbiota in patients with atherosclerosis. Proc Natl Acad Sci USA. 2011, 108: 4592-4598.PubMed

75.

Amar J, Lange C, Payros G, Garret C, Chabo C, Lantieri O, Courtney M, Marre M, Charles MA, Balkau B, Burcelin R: Blood microbiota dysbiosis is associated with the onset of cardiovascular events in a large general population: the d.e.s.I.R. Study. PLoS One. 2013, 8: e54461.PubMedPubMedCentral

76.

Koeth RA, Wang Z, Levison BS, Buffa JA, Org E, Sheehy BT, Britt EB, Fu X, Wu Y, Li L, Smith JD, Didonato JA, Chen J, Li H, Wu GD, Lewis JD, Warrier M, Brown JM, Krauss RM, Tang WH, Bushman FD, Lusis AJ: Hazen. 2013, Intestinal microbiota metabolism of l-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med: SL, 10.1038/nm.3145.

77.

Clark SE, Weiser JN: Microbial modulation of host immunity with the small molecule phosphorylcholine. Infect Immun. 2013, 81: 392-401.PubMedPubMedCentral

78.

Elkind MS: Infectious burden: a new risk factor and treatment target for atherosclerosis. Infect Disord Drug Targets. 2012, 10: 84-90.

79.

Haeggstrom JZ, Funk CD: Lipoxygenase and leukotriene pathways: biochemistry, biology, and roles in disease. Chem Rev. 2011, 111: 5866-5898.PubMed

80.

Qiu H, Gabrielsen A, Agardh HE, Wan M, Wetterholm A, Wong CH, Hedin U, Swedenborg J, Hansson GK, Samuelsson B, Paulsson-Berne G, Haeggström JZ: Expression of 5-lipoxygenase and leukotriene A4 hydrolase in human atherosclerotic lesions correlates with symptoms of plaque instability. Proc Natl Acad Sci USA. 2006, 103: 8161-8166.PubMedPubMedCentral

81.

Manzi S, Meilahn EN, Rairie JE, Conte CG, Medsger TA, Jansen-McWilliams L, D’Agostino RB, Kuller LH: Age-specific incidence rates of myocardial infarction and angina in women with systemic lupus erythematosus: comparison with the Framingham Study. Am J Epidemiol. 1997, 145: 408-415.PubMed

82.

Tyrrell PN, Beyene J, Feldman BM, McCrindle BW, Silverman ED, Bradley TJ: Rheumatic disease and carotid intima-media thickness a systematic review and meta-analysis. Arterioscler Thromb Vasc Biol. 2010, 30: 1014-1026.PubMed

83.

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

84.

Schwartz CJ, Mitchell JR: Cellular infiltration of the human arterial adventitia associated with atheromatous plaques. Circulation. 1962, 26: 73-78.PubMed

85.

Houtkamp MA, De Boer OJ, van der Loos CM, van der Wal AC, Becker AE: Adventitial infiltrates associated with advanced atherosclerotic plaques: structural organization suggests generation of local humoral immune responses. J Pathol. 2001, 193: 263-269.PubMed

86.

Stenmark KR, Yeager ME, El Kasmi KC, Nozik-Grayck E, Gerasimovskaya EV, Li M, Riddle SR, Frid MG: The adventitia: essential regulator of vascular wall structure and function. Annu Rev Physiol. 2013, 75: 23-47.PubMed

87.

Moos MP, John N, Grabner R, Nossmann S, Gunther B, Vollandt R, Funk CD, Kaiser B, Habenicht AJ: The lamina adventitia is the major site of immune cell accumulation in standard chow-fed apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol. 2005, 25: 2386-2391.PubMed

88.

Smith E, Prasad KM, Butcher M, Dobrian A, Kolls JK, Ley K, Galkina E: Blockade of interleukin-17A results in reduced atherosclerosis in apolipoprotein E-deficient mice. Circulation. 2010, 121: 1746-1755.PubMedPubMedCentral

89.

Kolodgie FD, Gold HK, Burke AP, Fowler DR, Kruth HS, Weber DK, Farb A, Guerrero LJ, Hayase M, Kutys R, Narula J, Finn AV, Virmani R: Intraplaque hemorrhage and progression of coronary atheroma. N Engl J Med. 2003, 349: 2316-2325.PubMed

90.

Falk E, Nakano M, Bentzon JF, Finn AV, Virmani R: Update on acute coronary syndromes: the pathologists’ view. Eur Heart J. 2013, 34: 719-728.PubMed

91.

David AR, Kershaw A, Heagerty A: Atherosclerosis and diet in ancient Egypt. Lancet. 2012, 375: 718-719.

92.

Murphy WA, Nedden DD, Gostner P, Knapp R, Recheis W, Seidler H: The iceman: discovery and imaging. Radiology. 2003, 226: 614-629.PubMed

93.

Rollo F, Ubaldi M, Ermini L, Marota I: Otzi’s last meals: DNA analysis of the intestinal content of the Neolithic glacier mummy from the Alps. Proc Natl Acad Sci USA. 2002, 99: 12594-12599.PubMedPubMedCentral

94.

Keller A, Graefen A, Ball M, Matzas M, Boisguerin V, Maixner F, Leidinger P, Backes C, Khairat R, Forster M, Stade B, Franke A, Mayer J, Spangler J, McLaughlin S, Shah M, Lee C, Harkins TT, Sartori A, Moreno-Estrada A, Henn B, Sikora M, Semino O, Chiaroni J, Rootsi S, Myres NM, Cabrera VM, Underhill PA, Bustamante CD, Vigl EE: New insights into the Tyrolean Iceman’s origin and phenotype as inferred by whole-genome sequencing. Nat Commun. 2012, 3: 698.PubMed

95.

Thompson RC, Allam AH, Lombardi GP, Wann LS, Sutherland ML, Sutherland JD, Soliman MA, Frohlich B, Mininberg DT, Monge JM, Vallodolid CM, Cox SL, Abd El-Maksoud G, Badr I, Miyamoto MI, El-Halim Nur El-Din A, Narula J, Finch CE, Thomas GS: Atherosclerosis across 4000 years of human history: the Horus study of four ancient populations. Lancet. 2013, 381: 1211-1222.PubMed

96.

Lindeberg S, Lundh B: Apparent absence of stroke and ischaemic heart disease in a traditional Melanesian island: a clinical study in Kitava. J Intern Med. 1993, 233: 269-275.PubMed

97.

Frostegard J, Tao W, Georgiades A, Rastam L, Lindblad U, Lindeberg S: Atheroprotective natural anti-phosphorylcholine antibodies of IgM subclass are decreased in Swedish controls as compared to non-westernized individuals from New Guinea. Nutr Metab (Lond). 2007, 4: 7.

98.

Blanco DR, Champion CI, Dooley A, Cox DL, Whitelegge JP, Faull K, Lovett MA: A monoclonal antibody that conveys in vitro killing and partial protection in experimental syphilis binds a phosphorylcholine surface epitope of Treponema pallidum. Infect Immun. 2005, 73: 3083-3095.PubMedPubMedCentral

99.

Lemogoum D, Ngatchou W, Janssen C, Leeman M, Van Bortel L, Boutouyrie P, Degaute JP, Van de Borne P: Effects of hunter-gatherer subsistence mode on arterial distensibility in Cameroonian pygmies. Hypertension. 2012, 60: 123-128.PubMed

100.

Burger O, Baudisch A, Vaupel JW: Human mortality improvement in evolutionary context. Proc Natl Acad Sci USA. 2012, 109: 18210-18214.PubMedPubMedCentral

101.

McCullagh KG: Arteriosclerosis in the African elephant. I. Intimal atherosclerosis and its possible causes. Atherosclerosis. 1972, 16: 307-335.PubMed

102.

Ghittoni R, Napolitani G, Benati D, Ulivieri C, Patrussi L, Laghi Pasini F, Lanzavecchia A, Baldari CT: Simvastatin inhibits the MHC class II pathway of antigen presentation by impairing Ras superfamily GTPases. Eur J Immunol. 2006, 36: 2885-2893.PubMed

103.

Wang CY, Liu PY, Liao JK: Pleiotropic effects of statin therapy: molecular mechanisms and clinical results. Trends Mol Med. 2008, 14: 37-44.PubMedPubMedCentral

104.

Ridker PM, Danielson E, Fonseca FA, Genest J, Gotto AM, Kastelein JJ, Koenig W, Libby P, Lorenzatti AJ, MacFadyen JG, Nordestgaard BG, Shepherd J, Willerson JT, Glynn RJ, JUPITER Study Group: Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008, 359: 2195-2207.PubMed

105.

Ridker PM: Moving beyond JUPITER: will inhibiting inflammation reduce vascular event rates?. Curr Atheroscler Rep. 2013, 15: 295.PubMed

106.

Micha R, Imamura F, Wyler Von Ballmoos M, Solomon DH, Hernan MA, Ridker PM, Mozaffarian D: Systematic review and meta-analysis of methotrexate use and risk of cardiovascular disease. Am J Cardiol. 2011, 108: 1362-1370.PubMedPubMedCentral

107.

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.PubMed

108.

Krishnan E, Lingala VB, Singh G: Declines in mortality from acute myocardial infarction in successive incidence and birth cohorts of patients with rheumatoid arthritis. Circulation. 2004, 110: 1774-1779.PubMed

109.

Bernatsky S, Hudson M, Suissa S: Anti-rheumatic drug use and risk of hospitalization for congestive heart failure in rheumatoid arthritis. Rheumatology (Oxford). 2005, 44: 677-680.

110.

Qamar A, Rader DJ: Effect of interleukin 1beta inhibition in cardiovascular disease. Curr Opin Lipidol. 2012, 23: 548-553.PubMed

111.

Subbanagounder G, Leitinger N, Shih PT, Faull KF, Berliner JA: Evidence that phospholipid oxidation products and/or platelet-activating factor play an important role in early atherogenesis: in vitro and in vivo inhibition by WEB 2086. Circ Res. 1999, 85: 311-318.PubMed

112.

Ewing MM, De Vries MR, Nordzell M, Pettersson K, De Boer HC, Van Zonneveld AJ, Frostegard J, Jukema JW, Quax PH: Annexin A5 therapy attenuates vascular inflammation and remodeling and improves endothelial function in mice. Arterioscler Thromb Vasc Biol. 2011, 31: 95-101.PubMed

113.

O’Donoghue ML, Braunwald E, White HD, Serruys P, Steg PG, Hochman J, Maggioni AP, Bode C, Weaver D, Johnson JL, Cicconetti G, Lukas MA, Tarka E, Cannon CP: Study design and rationale for the Stabilization of pLaques usIng Darapladib-Thrombolysis in Myocardial Infarction (SOLID-TIMI 52) trial in patients after an acute coronary syndrome. Am Heart J. 2011, 162: 613-619.PubMed

114.

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

115.

Fredrikson GN, Soderberg I, Lindholm M, Dimayuga P, Chyu KY, Shah PK, Nilsson J: Inhibition of atherosclerosis in apoE-null mice by immunization with apoB-100 peptide sequences. Arterioscler Thromb Vasc Biol. 2003, 23: 879-884.PubMed

116.

Strom A, Fredrikson GN, Schiopu A, Ljungcrantz I, Soderberg I, Jansson B, Carlsson R, Hultgardh-Nilsson A, Nilsson J: Inhibition of injury-induced arterial remodelling and carotid atherosclerosis by recombinant human antibodies against aldehyde-modified apoB-100. Atherosclerosis. 2007, 190: 298-305.PubMed

117.

Schiopu A, Bengtsson J, Soderberg I, Janciauskiene S, Lindgren S, Ares MP, Shah PK, Carlsson R, Nilsson J, Fredrikson GN: Recombinant human antibodies against aldehyde-modified apolipoprotein B-100 peptide sequences inhibit atherosclerosis. Circulation. 2004, 110: 2047-2052.PubMed

118.

BioInvent announces data from BI-204 phase IIa study on stable atherosclerotic vascular disease. 2012, http://www.news-medical.net/news/20120711/BioInvent-announces-data-from-BI-204-phase-IIa-study-on-stable-atherosclerotic-vascular-disease.aspx.

119.

Chen Y, Khanna S, Goodyear CS, Park YB, Raz E, Thiel S, Gronwall C, Vas J, Boyle DL, Corr M, Kono DH, Silverman GJ: Regulation of dendritic cells and macrophages by an anti-apoptotic cell natural antibody that suppresses TLR responses and inhibits inflammatory arthritis. J Immunol. 2009, 183: 1346-1359.PubMedPubMedCentral

120.

Nicoletti A, Kaveri S, Caligiuri G, Bariety J, Hansson GK: Immunoglobulin treatment reduces atherosclerosis in apo E knockout mice. J Clin Invest. 1998, 102: 910-918.PubMedPubMedCentral

121.

Long J, Lin J, Yang X, Yuan D, Wu J, Li T, Cao R, Liu J: Nasal immunization with different forms of heat shock protein-65 reduced high-cholesterol-diet-driven rabbit atherosclerosis. Int Immunopharmacol. 2012, 13: 82-87.PubMed

122.

Jun L, Jie L, Dongping Y, Xin Y, Taiming L, Rongyue C, Jie W, Jingjing L: Effects of nasal immunization of multi-target preventive vaccines on atherosclerosis. Vaccine. 2012, 30: 1029-1037.PubMed

123.

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.PubMed

124.

Li J, Zhao X, Zhang S, Wang S, Du P, Qi G: ApoB-100 and HSP60 peptides exert a synergetic role in inhibiting early atherosclerosis in immunized ApoE-null mice. Protein Pept Lett. 2011, 18: 733-740.PubMed

The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1741-7015/11/117/prepub

Title: Immunity, atherosclerosis and cardiovascular disease
Author: Johan Frostegård
Publication date: 01-12-2013
Publisher: BioMed Central
Published in: BMC Medicine / Issue 1/2013
Electronic ISSN: 1741-7015
DOI: https://doi.org/10.1186/1741-7015-11-117

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Immunity, atherosclerosis and cardiovascular disease

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2013

Worse prognosis of KRASc.35 G > A mutant metastatic colorectal cancer (MCRC) patients treated with intensive triplet chemotherapy plus bevacizumab (FIr-B/FOx)

Body mass index and incident coronary heart disease in women: a population-based prospective study

Developmental heterochrony and the evolution of autistic perception, cognition and behavior

Targeted rotavirus vaccination of high-risk infants; a low cost and highly cost-effective alternative to universal vaccination

Additional Saturday rehabilitation improves functional independence and quality of life and reduces length of stay: a randomized controlled trial

The differential role of androgens in early human sex development