Download PDF
Thromb Haemost 2013; 109(05): 854-868
DOI: 10.1160/TH12-10-0768
Review Article
Schattauer GmbH

Evidence on the pathogenic role of auto-antibodies in acute cardiovascular diseases

Federico Carbone
1   Department of Internal Medicine, University of Genoa, Genoa, Italy
,
Alessio Nencioni
1   Department of Internal Medicine, University of Genoa, Genoa, Italy
,
François Mach
2   Division of Cardiology, Foundation for Medical Researches, Faculty of Medicine, Department of Internal Medicine, Geneva University Hospital, Geneva, Switzerland
,
Nicolas Vuilleumier   *
3   Division of Laboratory Medicine, Department of Genetics and Laboratory Medicine, Geneva University Hospitals, Switzerland
4   Department of Human Protein Science, Geneva Faculty of Medicine, Geneva, Switzerland
,
Fabrizio Montecucco   *
1   Department of Internal Medicine, University of Genoa, Genoa, Italy
2   Division of Cardiology, Foundation for Medical Researches, Faculty of Medicine, Department of Internal Medicine, Geneva University Hospital, Geneva, Switzerland
› Author Affiliations
Further Information

Publication History

Received: 23 October 2012

Accepted after major revision: 29 January 2013

Publication Date:
22 November 2017 (online)

Also available at
    Permissions and Reprints

Summary

Atherothrombosis is the major determinant of acute ischaemic cardiovascular events, such as myocardial infarction and stroke. Inflammatory processes have been linked to all phases of atherogenesis In particular, the identification of autoimmunity mediators in the complex microenvironment of chronic inflammation has become the focus of attention in both early and advanced atherogenic processes. Autoantibodies against self-molecules or new epitopes generated by oxidative processes infiltrate atherosclerotic plaques and were shown to modulate the activity of immune cells by binding various types of receptors. However, despite mounting evidence for a pathophysiological role of autoantibodies in atherothrombosis, the clinical relevance for circulating autoantibodies in cardiovascular outcomes is still debated. This review aims at illustrating the mechanisms by which different types of autoantibodies might either promote or repress atherothrombosis and to discuss the clinical studies assessing the role of auto-antibodies as prognostic biomarkers of plaque vulnerability.

Keywords

Atherosclerosis - auto-antibodies - inflammation - acute myocardial infarction - stroke

* Equal senior authorship.


 

  • References

  • 1 Ross R. Atherosclerosis--an inflammatory disease. N Engl J Med 1999; 340: 115-126.
    CrossrefPubMedGoogle Scholar
  • 2 Yan ZQ, Hansson GK. Innate immunity, macrophage activation, and atherosclerosis. Immunol Rev 2007; 219: 187-203.
    CrossrefPubMedGoogle Scholar
  • 3 Packard RR, Libby P. Inflammation in atherosclerosis: from vascular biology to biomarker discovery and risk prediction. Clin Chem 2008; 54: 24-38.
    PubMedGoogle Scholar
  • 4 Tabas I, Williams KJ, Boren J. Subendothelial lipoprotein retention as the initiating process in atherosclerosis: update and therapeutic implications. Circulation 2007; 116: 1832-1844.
    CrossrefPubMedGoogle Scholar
  • 5 Libby P, Ridker PM, Hansson GK. Progress and challenges in translating the biology of atherosclerosis. Nature 2011; 473: 317-325.
    CrossrefPubMedGoogle Scholar
  • 6 Hansson GK, Libby P. The immune response in atherosclerosis: a double-edged sword. Nat Rev Immunol 2006; 06: 508-519.
    CrossrefPubMedGoogle Scholar
  • 7 Binder CJ, Chang MK, Shaw PX. et al. Innate and acquired immunity in atherogenesis. Nat Med 2002; 08: 1218-1226.
    CrossrefPubMedGoogle Scholar
  • 8 Dumitriu IE, Kaski JC. The role of T and B cells in atherosclerosis: potential clinical implications. Curr Pharm Des 2011; 17: 4159-4171.
    CrossrefPubMedGoogle Scholar
  • 9 Campbell KA, Lipinski MJ, Doran AC. et al. Lymphocytes and the adventitial immune response in atherosclerosis. Circ Res 2012; 110: 889-900.
    CrossrefPubMedGoogle Scholar
  • 10 Kyaw T, Tipping P, Toh BH. et al. Current understanding of the role of B cell subsets and intimal and adventitial B cells in atherosclerosis. Curr Opin Lipidol 2011; 22: 373-379.
    CrossrefPubMedGoogle Scholar
  • 11 Kyaw T, Tipping P, Bobik A. et al. Protective role of natural IgM-producing B1a cells in atherosclerosis. Trends Cardiovasc Med 2012; 22: 48-53.
    CrossrefPubMedGoogle Scholar
  • 12 Kyaw T, Tay C, Khan A. et al. Conventional B2 B cell depletion ameliorates whereas its adoptive transfer aggravates atherosclerosis. J Immunol 2010; 185: 4410-4419.
    CrossrefPubMedGoogle Scholar
  • 13 Harris DP, Haynes L, Sayles PC. et al. Reciprocal regulation of polarized cytokine production by effector B and T cells. Nat Immunol 2000; 01: 475-482.
    CrossrefPubMedGoogle Scholar
  • 14 Blank M, Shoenfeld Y. Beta-2-glycoprotein-I, infections, antiphospholipid syndrome and therapeutic considerations. Clin Immunol 2004; 112: 190-199.
    CrossrefPubMedGoogle Scholar
  • 15 Hall JC, Casciola-Rosen L, Rosen A. Altered structure of autoantigens during apoptosis. Rheum Dis Clin North Am 2004; 30: 455-471. vii
    CrossrefPubMedGoogle Scholar
  • 16 Stemme S, Faber B, Holm J. et al. T lymphocytes from human atherosclerotic plaques recognize oxidized low density lipoprotein. Proc Natl Acad Sci USA 1995; 92: 3893-3897.
    CrossrefPubMedGoogle Scholar
  • 17 Sherer Y, Shoenfeld Y. Mechanisms of disease: atherosclerosis in autoimmune diseases. Nat Clin Pract Rheumatol 2006; 02: 99-106.
    PubMedGoogle Scholar
  • 18 Flood C, Gustafsson M, Pitas RE. et al. Molecular mechanism for changes in proteoglycan binding on compositional changes of the core and the surface of low-density lipoprotein-containing human apolipoprotein B100. Arterioscler Thromb Vasc Biol 2004; 24: 564-570.
    CrossrefPubMedGoogle Scholar
  • 19 Chahine MN, Blackwood DP, Dibrov E. et al. Oxidized LDL affects smooth muscle cell growth through MAPK-mediated actions on nuclear protein import. J Mol Cell Cardiol 2009; 46: 431-441.
    CrossrefPubMedGoogle Scholar
  • 20 Auge N, Garcia V, Maupas-Schwalm F. et al. Oxidized LDL-induced smooth muscle cell proliferation involves the EGF receptor/PI-3 kinase/Akt and the sphingolipid signalling pathways. Arterioscler Thromb Vasc Biol 2002; 22: 1990-1995.
    CrossrefPubMedGoogle Scholar
  • 21 Fruhwirth GO, Moumtzi A, Loidl A. et al. The oxidized phospholipids POVPC and PGPC inhibit growth and induce apoptosis in vascular smooth muscle cells. Biochim Biophys Acta 2006; 1761: 1060-1069.
    CrossrefPubMedGoogle Scholar
  • 22 Gargalovic PS, Imura M, Zhang B. et al. Identification of inflammatory gene modules based on variations of human endothelial cell responses to oxidized lipids. Proc Natl Acad Sci USA 2006; 103: 12741-12746.
    CrossrefPubMedGoogle Scholar
  • 23 Beckman JS, Koppenol WH. Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly. Am J Physiol 1996; 271: C1424-1437.
    CrossrefPubMedGoogle Scholar
  • 24 Mitra S, Goyal T, Mehta JL. Oxidized LDL, LOX-1 and atherosclerosis. Cardiovasc Drugs Ther 2011; 25: 419-429.
    CrossrefPubMedGoogle Scholar
  • 25 Kugiyama K, Sakamoto T, Misumi I. et al. Transferable lipids in oxidized low-density lipoprotein stimulate plasminogen activator inhibitor-1 and inhibit tissue-type plasminogen activator release from endothelial cells. Circ Res 1993; 73: 335-343.
    CrossrefPubMedGoogle Scholar
  • 26 Kzhyshkowska J, Neyen C, Gordon S. Role of macrophage scavenger receptors in atherosclerosis. Immunobiology 2012; 217: 492-502.
    CrossrefPubMedGoogle Scholar
  • 27 Namgaladze D, Morbitzer D, von Knethen A. et al. Phospholipase A2-modified low-density lipoprotein activates macrophage peroxisome proliferator-activated receptors. Arterioscler Thromb Vasc Biol 2010; 30: 313-320.
    CrossrefPubMedGoogle Scholar
  • 28 Lee H, Shi W, Tontonoz P. et al. Role for peroxisome proliferator-activated receptor alpha in oxidized phospholipid-induced synthesis of monocyte chemotactic protein-1 and interleukin-8 by endothelial cells. Circ Res 2000; 87: 516-521.
    CrossrefPubMedGoogle Scholar
  • 29 Marathe GK, Zimmerman GA, Prescott SM. et al. Activation of vascular cells by PAF-like lipids in oxidized LDL. Vascul Pharmacol 2002; 38: 193-200.
    CrossrefPubMedGoogle Scholar
  • 30 Miller YI, Viriyakosol S, Worrall DS. et al. Toll-like receptor 4-dependent and -independent cytokine secretion induced by minimally oxidized low-density lipoprotein in macrophages. Arterioscler Thromb Vasc Biol 2005; 25: 1213-1219.
    CrossrefPubMedGoogle Scholar
  • 31 Verstrepen L, Bekaert T, Chau TL. et al. TLR-4, IL-1R and TNF-R signalling to NF-kappaB: variations on a common theme. Cell Mol Life Sci 2008; 65: 2964-2978.
    CrossrefPubMedGoogle Scholar
  • 32 Palinski W, Yla-Herttuala S, Rosenfeld ME. et al. Antisera and monoclonal antibodies specific for epitopes generated during oxidative modification of low density lipoprotein. Arteriosclerosis 1990; 10: 325-335.
    CrossrefPubMedGoogle Scholar
  • 33 Yla-Herttuala S, Palinski W, Butler SW. et al. Rabbit and human atherosclerotic lesions contain IgG that recognizes epitopes of oxidized LDL. Arterioscler Thromb 1994; 14: 32-40.
    CrossrefPubMedGoogle Scholar
  • 34 Mironova M, Virella G, Lopes-Virella MF. Isolation and characterisation of human antioxidized LDL autoantibodies. Arterioscler Thromb Vasc Biol 1996; 16: 222-229.
    CrossrefPubMedGoogle Scholar
  • 35 Virella G, Koskinen S, Krings G. et al. Immunochemical characterisation of purified human oxidized low-density lipoprotein antibodies. Clin Immunol 2000; 95: 135-144.
    CrossrefPubMedGoogle Scholar
  • 36 Salonen JT, Yla-Herttuala S, Yamamoto R. et al. Autoantibody against oxidised LDL and progression of carotid atherosclerosis. Lancet 1992; 339: 883-887.
    CrossrefPubMedGoogle Scholar
  • 37 Witztum JL, Hörkkö S. The role of oxidized LDL in atherogenesis: immunological response and anti-phospholipid antibodies. Ann NY Acad Sci 1997; 811: 88-96.
    CrossrefPubMedGoogle Scholar
  • 38 Ehrenstein MR, Notley CA. The importance of natural IgM: scavenger, protector and regulator. Nat Rev Immunol 2010; 10: 778-786.
    CrossrefPubMedGoogle Scholar
  • 39 Roux-Lombard P, Pagano S, Montecucco F. et al. Auto-antibodies as Emergent Prognostic Markers and Possible Mediators of Ischaemic Cardiovascular Diseases. Clin Rev Allergy Immunol 2013; 44: 84-97.
    CrossrefPubMedGoogle Scholar
  • 40 Bellomo G, Maggi E, Poli M. et al. Autoantibodies against oxidatively modified low-density lipoproteins in NIDDM. Diabetes 1995; 44: 60-66.
    CrossrefPubMedGoogle Scholar
  • 41 Erkkila AT, Narvanen O, Lehto S. et al. Autoantibodies against oxidized low-density lipoprotein and cardiolipin in patients with coronary heart disease. Arterioscler Thromb Vasc Biol 2000; 20: 204-209.
    CrossrefPubMedGoogle Scholar
  • 42 Lehtimaki T, Lehtinen S, Solakivi T. et al. Autoantibodies against oxidized low density lipoprotein in patients with angiographically verified coronary artery disease. Arterioscler Thromb Vasc Biol 1999; 19: 23-27.
    CrossrefPubMedGoogle Scholar
  • 43 Maggi E, Chiesa R, Melissano G. et al. LDL oxidation in patients with severe carotid atherosclerosis. A study of in vitro and in vivo oxidation markers. Arterioscler Thromb 1994; 14: 1892-1899.
    CrossrefPubMedGoogle Scholar
  • 44 Mustafa A, Nityanand S, Berglund L. et al. Circulating immune complexes in 50-year-old men as a strong and independent risk factor for myocardial infarction. Circulation 2000; 102: 2576-2581.
    CrossrefPubMedGoogle Scholar
  • 45 Virella G, Virella I, Leman RB. et al. Anti-oxidized low-density lipoprotein antibodies in patients with coronary heart disease and normal healthy volunteers. Int J Clin Lab Res 1993; 23: 95-101.
    CrossrefPubMedGoogle Scholar
  • 46 Wilson PW, Ben-Yehuda O, McNamara J. et al. Autoantibodies to oxidized LDL and cardiovascular risk: the Framingham Offspring Study. Atherosclerosis 2006; 189: 364-368.
    CrossrefPubMedGoogle Scholar
  • 47 Ravandi A, Boekholdt SM, Mallat Z. et al. Relationship of IgG and IgM autoantibodies and immune complexes to oxidized LDL with markers of oxidation and inflammation and cardiovascular events: results from the EPIC-Norfolk Study. J Lipid Res 2011; 52: 1829-1836.
    CrossrefPubMedGoogle Scholar
  • 48 Karvonen J, Päivänsalo M, Kesäniemi YA. et al. Immunoglobulin M type of autoantibodies to oxidized low-density lipoprotein has an inverse relation to carotid artery atherosclerosis. Circulation 2003; 108: 2107-2112.
    CrossrefPubMedGoogle Scholar
  • 49 Tsimikas S, Brilakis ES, Lennon RJ. et al. Relationship of IgG and IgM autoantibodies to oxidized low density lipoprotein with coronary artery disease and cardiovascular events. J Lipid Res 2007; 48: 425-433.
    CrossrefPubMedGoogle Scholar
  • 50 Oksjoki R, Kovanen PT, Lindstedt KA. et al. OxLDL-IgG immune complexes induce survival of human monocytes. Arterioscler Thromb Vasc Biol 2006; 26: 576-583.
    PubMedGoogle Scholar
  • 51 Nagarajan S. Anti-OxLDL IgG blocks OxLDL interaction with CD36, but promotes FcgammaR, CD32A–dependent inflammatory cell adhesion. Immunol Lett 2007; 108: 52-61.
    CrossrefPubMedGoogle Scholar
  • 52 Crowley MT, Costello PS, Fitzer-Attas CJ. et al. A critical role for Syk in signal transduction and phagocytosis mediated by Fcgamma receptors on macrophages. J Exp Med 1997; 186: 1027-1039.
    CrossrefPubMedGoogle Scholar
  • 53 Saad AF, Virella G, Chassereau C. et al. OxLDL immune complexes activate complement and induce cytokine production by MonoMac 6 cells and human macrophages. J Lipid Res 2006; 47: 1975-1983.
    CrossrefPubMedGoogle Scholar
  • 54 Virella G, Atchley D, Koskinen S. et al. Proatherogenic and proinflammatory properties of immune complexes prepared with purified human oxLDL antibodies and human oxLDL. Clin Immunol 2002; 105: 81-92.
    CrossrefPubMedGoogle Scholar
  • 55 Lopes-Virella MF, Griffith RL, Shunk KA. et al. Enhanced uptake and impaired intracellular metabolism of low density lipoprotein complexed with anti-low density lipoprotein antibodies. Arterioscler Thromb 1991; 11: 1356-1367.
    CrossrefPubMedGoogle Scholar
  • 56 Tohyama Y, Yamamura H. Protein tyrosine kinase, syk: a key player in phagocytic cells. J Biochem 2009; 145: 267-273.
    CrossrefPubMedGoogle Scholar
  • 57 Luo Y, Pollard JW, Casadevall A. Fcgamma receptor cross-linking stimulates cell proliferation of macrophages via the ERK pathway. J Biol Chem 2010; 285: 4232-4242.
    CrossrefPubMedGoogle Scholar
  • 58 Datta SR, Brunet A, Greenberg ME. Cellular survival: a play in three Akts. Genes Dev 1999; 13: 2905-2927.
    CrossrefPubMedGoogle Scholar
  • 59 Smith KJ, Twal WO, Soodavar F. et al. Heat shock protein 70B’ (HSP70B’) expression and release in response to human oxidized low density lipoprotein immune complexes in macrophages. J Biol Chem 2010; 285: 15985-15993.
    CrossrefPubMedGoogle Scholar
  • 60 Hammad SM, Twal WO, Barth JL. et al. Oxidized LDL immune complexes and oxidized LDL differentially affect the expression of genes involved with inflammation and survival in human U937 monocytic cells. Atherosclerosis 2009; 202: 394-404.
    CrossrefPubMedGoogle Scholar
  • 61 Lopes-Virella MF, Hunt KJ, Baker NL. et al. Levels of oxidized LDL and advanced glycation end products-modified LDL in circulating immune complexes are strongly associated with increased levels of carotid intima-media thickness and its progression in type 1 diabetes. Diabetes 2011; 60: 582-589.
    CrossrefPubMedGoogle Scholar
  • 62 Lopes-Virella MF, Baker NL, Hunt KJ. et al. Oxidized LDL immune complexes and coronary artery calcification in type 1 diabetes. Atherosclerosis 2011; 214: 462-467.
    CrossrefPubMedGoogle Scholar
  • 63 Chou MY, Hartvigsen K, Hansen LF. et al. Oxidation-specific epitopes are important targets of innate immunity. J Intern Med 2008; 263: 479-488.
    CrossrefPubMedGoogle Scholar
  • 64 Sher A, Cohn M. Effect of haptens on the reaction of anti-idiotype antibody with a mouse anti-phosphorylcholine plasmacytoma protein. J Immunol 1972; 109: 176-178.
    PubMedGoogle Scholar
  • 65 Claflin JL, Davie JM. Clonal nature of the immune response to phosphorylcholine. III. Species-specific binding characteristics of rodent anti-phosphorylcholine antibodies. J Immunol 1974; 113: 1678-1684.
    PubMedGoogle Scholar
  • 66 Riesen W, Rudikoff S, Oriol R, Potter M. An IgM Waldenström with specificity against phosphorylcholine. Biochemistry 1975; 14: 1052-1057.
    CrossrefPubMedGoogle Scholar
  • 67 Péry P, Luffau G, Charley J. et al. Phosphorylcholine antigens from Nippostrongylus brasiliensis. I.--Anti-phosphorylcholine antibodies in infected rats and location of phosphorylcholine antigens. Ann Immunol 1979; 130: 879-888.
    PubMedGoogle Scholar
  • 68 Shaw PX, Hörkkö S, Chang MK. et al. Natural antibodies with the T15 idiotype may act in atherosclerosis, apoptotic clearance, and protective immunity. J Clin Invest 2000; 105: 1731-1740.
    CrossrefPubMedGoogle Scholar
  • 69 Binder CJ, Hörkkö S, Dewan A. et al. Pneumococcal vaccination decreases atherosclerotic lesion formation: molecular mimicry between Streptococcus pneumoniae and oxidized LDL. Nat Med 2003; 09: 736-743.
    CrossrefPubMedGoogle Scholar
  • 70 Shaw PX, Horkko S, Tsimikas S. et al. Human-derived anti-oxidized LDL autoantibody blocks uptake of oxidized LDL by macrophages and localizes to atherosclerotic lesions in vivo. Arterioscler Thromb Vasc Biol 2001; 21: 1333-1339.
    CrossrefPubMedGoogle Scholar
  • 71 Su J, Hua X, Concha H. et al. Natural antibodies against phosphorylcholine as potential protective factors in SLE. Rheumatology 2008; 47: 1144-1150.
    CrossrefPubMedGoogle Scholar
  • 72 Su J, Georgiades A, Wu R. et al. Antibodies of IgM subclass to phosphorylcholine and oxidized LDL are protective factors for atherosclerosis in patients with hypertension. Atherosclerosis 2006; 188: 160-166.
    CrossrefPubMedGoogle Scholar
  • 73 Sjoberg BG, Su J, Dahlbom I. et al. Low levels of IgM antibodies against phosphorylcholine-A potential risk marker for ischaemic stroke in men. Atherosclerosis 2009; 203: 528-532.
    CrossrefPubMedGoogle Scholar
  • 74 Fiskesund R, Stegmayr B, Hallmans G. et al. Low levels of antibodies against phosphorylcholine predict development of stroke in a population-based study from northern Sweden. Stroke 2010; 41: 607-612.
    CrossrefPubMedGoogle Scholar
  • 75 Carrero JJ, Hua X, Stenvinkel P. et al. Low levels of IgM antibodies against phosphorylcholine-A increase mortality risk in patients undergoing haemodialysis. Nephrol Dial Transplant 2009; 24: 3454-3460.
    CrossrefPubMedGoogle Scholar
  • 76 Anania C, Gustafsson T, Hua X. et al. 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.
    CrossrefPubMedGoogle Scholar
  • 77 de Faire U, Su J, Hua X. et al. 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.
    CrossrefPubMedGoogle Scholar
  • 78 Grönlund H, Hallmans G, Jansson JH. et al. Low levels of IgM antibodies against phosphorylcholine predict development of acute myocardial infarction in a population-based cohort from northern Sweden. Eur J Cardiovasc Prev Rehabil 2009; 16: 382-386.
    CrossrefPubMedGoogle Scholar
  • 79 Caidahl K, Hartford M, Karlsson T. et al. IgM-phosphorylcholine autoantibodies and outcome in acute coronary syndromes. Int J Cardiol. 2012 epub ahead of print
    PubMedGoogle Scholar
  • 80 Keller PF, Pagano S, Roux-Lombard P. et al. Autoantibodies against apolipoprotein A-1 and phosphorylcholine for diagnosis of non-ST-segment elevation myocardial infarction. J Intern Med 2012; 271: 451-462.
    CrossrefPubMedGoogle Scholar
  • 81 Glomset JA. Physiological role of lecithin-cholesterol acyltransferase. Am J Clin Nutr 1970; 23: 1129-1136.
    CrossrefPubMedGoogle Scholar
  • 82 Mackness MI, Arrol S, Abbott C. et al. Protection of low-density lipoprotein against oxidative modification by high-density lipoprotein associated paraoxonase. Atherosclerosis 1993; 104: 129-135.
    CrossrefPubMedGoogle Scholar
  • 83 Marathe GK, Zimmerman GA, McIntyre TM. Platelet-activating factor acetylhydrolase, and not paraoxonase-1, is the oxidized phospholipid hydrolase of high density lipoprotein particles. J Biol Chem 2003; 278: 3937-3947.
    CrossrefPubMedGoogle Scholar
  • 84 Hyka N, Dayer JM, Modoux C. et al. Apolipoprotein A-I inhibits the production of interleukin-1beta and tumor necrosis factor-alpha by blocking contact-mediated activation of monocytes by T lymphocytes. Blood 2001; 97: 2381-2389.
    CrossrefPubMedGoogle Scholar
  • 85 Barter PJ, Baker PW, Rye KA. Effect of high-density lipoproteins on the expression of adhesion molecules in endothelial cells. Curr Opin Lipidol 2002; 13: 285-288.
    CrossrefPubMedGoogle Scholar
  • 86 Navab M, Reddy ST, Van Lenten BJ. et al. The role of dysfunctional HDL in atherosclerosis. J Lipid Res 2009; 450 (Suppl) S145-149.
    PubMedGoogle Scholar
  • 87 Tsompanidi EM, Brinkmeier MS, Fotiadou EH. et al. HDL biogenesis and functions: role of HDL quality and quantity in atherosclerosis. Atherosclerosis 2010; 208: 3-9.
    CrossrefPubMedGoogle Scholar
  • 88 Dinu AR, Merrill JT, Shen C. et al. Frequency of antibodies to the cholesterol transport protein apolipoprotein A1 in patients with SLE. Lupus 1998; 07: 355-360.
    CrossrefPubMedGoogle Scholar
  • 89 Delgado Alves J, Ames PR, Donohue S. et al. Antibodies to high-density lipoprotein and beta2-glycoprotein I are inversely correlated with paraoxonase activity in systemic lupus erythematosus and primary antiphospholipid syndrome. Arthritis Rheum 2002; 46: 2686-2694.
    CrossrefPubMedGoogle Scholar
  • 90 Vuilleumier N, Reber G, James R. et al. Presence of autoantibodies to apolipoprotein A-1 in patients with acute coronary syndrome further links autoimmunity to cardiovascular disease. J Autoimmun 2004; 23: 353-360.
    CrossrefPubMedGoogle Scholar
  • 91 Vuilleumier N, Bas S, Pagano S. et al. Anti-apolipoprotein A-1 IgG predicts major cardiovascular events in patients with rheumatoid arthritis. Arthritis Rheum 2010; 62: 2640-2650.
    CrossrefPubMedGoogle Scholar
  • 92 Finckh A, Courvoisier DS, Pagano S. et al. Evaluation of cardiovascular risk in patients with rheumatoid arthritis: do cardiovascular biomarkers offer added predictive ability over established clinical risk scores?. Arthritis Care Res 2012; 64: 817-825.
    CrossrefPubMedGoogle Scholar
  • 93 Vuilleumier N, Rossier MF, Pagano S. et al. Anti-apolipoprotein A-1 IgG as an independent cardiovascular prognostic marker affecting basal heart rate in myocardial infarction. Eur Heart J 2010; 31: 815-823.
    CrossrefPubMedGoogle Scholar
  • 94 Vuilleumier N, Pagano S, Lalhou K, Poncet A, Charbonney E, Norman GL, Mach F, Roux-Lombard P. Head-to-Head Comparison of Auto-Antibodies for Cardiovascular Outcome Prediction after Myocardial Infarction: a Prospective Study. J Clinic Experiment Cardiol. 2011 epub ahead of print
    PubMedGoogle Scholar
  • 95 Vuilleumier N, Charbonney E, Fontao L. et al. Anti-(apolipoprotein A-1) IgGs are associated with high levels of oxidized low-density lipoprotein in acute coronary syndrome. Clin Sci 2008; 115: 25-33.
    CrossrefPubMedGoogle Scholar
  • 96 Yuhanna IS, Zhu Y, Cox BE. et al. High-density lipoprotein binding to scavenger receptor-BI activates endothelial nitric oxide synthase. Nat Med 2001; 07: 853-857.
    CrossrefPubMedGoogle Scholar
  • 97 Rossier MF, Pagano S, Python M. et al. Antiapolipoprotein A-1 IgG chronotropic effects require nongenomic action of aldosterone on L-type calcium channels. Endocrinology 2012; 153: 1269-1278.
    CrossrefPubMedGoogle Scholar
  • 98 Montecucco F, Vuilleumier N, Pagano S. et al. Anti-Apolipoprotein A-1 autoantibodies are active mediators of atherosclerotic plaque vulnerability. Eur Heart J 2011; 32: 412-421.
    CrossrefPubMedGoogle Scholar
  • 99 Pagano S, Satta N, Werling D. et al. Anti-apolipoprotein A-1 IgG in patients with myocardial infarction promotes inflammation through TLR2/CD14 complex. J Intern Med 2012; 272: 344-357.
    CrossrefPubMedGoogle Scholar
  • 100 Nakata T, Yasuda M, Fujita M. et al. CD14 directly binds to triacylated lipopeptides and facilitates recognition of the lipopeptides by the receptor complex of Toll-like receptors 2 and 1 without binding to the complex. Cell Microbiol 2006; 08: 1899-1909.
    CrossrefPubMedGoogle Scholar
  • 101 Raschi E, Testoni C, Bosisio D. et al. Role of the MyD88 transduction signalling pathway in endothelial activation by antiphospholipid antibodies. Blood 2003; 101: 3495-3500.
    CrossrefPubMedGoogle Scholar
  • 102 Satta N, Dunoyer-Geindre S, Reber G. et al. The role of TLR2 in the inflammatory activation of mouse fibroblasts by human antiphospholipid antibodies. Blood 2007; 109: 1507-1514.
    CrossrefPubMedGoogle Scholar
  • 103 Satta N, Kruithof EK, Fickentscher C. et al. Toll-like receptor 2 mediates the activation of human monocytes and endothelial cells by antiphospholipid antibodies. Blood 2011; 117: 5523-5531.
    CrossrefPubMedGoogle Scholar
  • 104 Van Lenten BJ, Hama SY, de Beer FC. et al. Anti-inflammatory HDL becomes pro-inflammatory during the acute phase response. Loss of protective effect of HDL against LDL oxidation in aortic wall cell cocultures. J Clin Invest 1995; 96: 2758-2767.
    CrossrefPubMedGoogle Scholar
  • 105 Delgado Alves J, Ames PR, Donohue S. et al. Antibodies to high-density lipoprotein and beta2-glycoprotein I are inversely correlated with paraoxonase activity in systemic lupus erythematosus and primary antiphospholipid syndrome. Arthritis Rheum 2002; 46: 2686-2694.
    CrossrefPubMedGoogle Scholar
  • 106 Batuca JR, Ames PR, Isenberg DA, Alves JD. Antibodies toward high-density lipoprotein components inhibit paraoxonase activity in patients with systemic lupus erythematosus. Ann NY Acad Sci 2007; 1108: 137-146.
    CrossrefPubMedGoogle Scholar
  • 107 Ames PR, Matsuura E, Batuca JR. et al. High-density lipoprotein inversely relates to its specific autoantibody favoring oxidation in thrombotic primary antiphospholipid syndrome. Lupus 2010; 19: 711-716.
    CrossrefPubMedGoogle Scholar
  • 108 Srivastava R, Yu S, Parks BW. et al. Autoimmune-mediated reduction of high-density lipoprotein-cholesterol and paraoxonase 1 activity in systemic lupus erythematosus-prone gld mice. Arthritis Rheum 2011; 63: 201-211.
    CrossrefPubMedGoogle Scholar
  • 109 Wick PA, Mombelli A, Pagano S. et al. Anti-apolipoprotein A-1 autoantibodies as biomarker for atherosclerosis burden in patients with periodontitis. J Periodontal Res. 2012 epub ahead of print
    PubMedGoogle Scholar
  • 110 Mayer MP. Gymnastics of molecular chaperones. Mol Cell 2010; 39: 321-331.
    CrossrefPubMedGoogle Scholar
  • 111 Shan YX, Liu TJ, Su HF. et al. Hsp10 and Hsp60 modulate Bcl-2 family and mitochondria apoptosis signalling induced by doxorubicin in cardiac muscle cells. J Mol Cell Cardiol 2003; 35: 1135-1143.
    CrossrefPubMedGoogle Scholar
  • 112 Badrichani AZ, Stroka DM, Bilbao G. et al. Bcl-2 and Bcl-XL serve an anti-inflammatory function in endothelial cells through inhibition of NF-kappaB. J Clin Invest 1999; 103: 543-553.
    CrossrefPubMedGoogle Scholar
  • 113 Ferns G, Shams S, Shafi S. Heat shock protein 27: its potential role in vascular disease. Int J Exp Pathol 2006; 87: 253-274.
    CrossrefPubMedGoogle Scholar
  • 114 Kostenko S, Moens U. Heat shock protein 27 phosphorylation: kinases, phosphatases, functions and pathology. Cell Mol Life Sci 2009; 66: 3289-3307.
    CrossrefPubMedGoogle Scholar
  • 115 Welch WJ, Suhan JP. Cellular and biochemical events in mammalian cells during and after recovery from physiological stress. J Cell Biol 1986; 103: 2035-2052.
    CrossrefPubMedGoogle Scholar
  • 116 Benjamin IJ, McMillan DR. Stress (heat shock) proteins: molecular chaperones in cardiovascular biology and disease. Circ Res 1998; 83: 117-132.
    CrossrefPubMedGoogle Scholar
  • 117 Han Z, Truong QA, Park S. et al. Two Hsp70 family members expressed in atherosclerotic lesions. Proc Natl Acad Sci USA 2003; 100: 1256-1261.
    CrossrefPubMedGoogle Scholar
  • 118 Zhu W, Roma P, Pellegatta F. et al. Oxidized-LDL induce the expression of heat shock protein 70 in human endothelial cells. Biochem Biophys Res Commun 1994; 200: 389-394.
    CrossrefPubMedGoogle Scholar
  • 119 Zhu WM, Roma P, Pirillo A. et al. Oxidized LDL induce hsp70 expression in human smooth muscle cells. FEBS Lett 1995; 372: 1-5.
    CrossrefPubMedGoogle Scholar
  • 120 Bobryshev YV, Lord RS. Expression of heat shock protein-70 by dendritic cells in the arterial intima and its potential significance in atherogenesis. J Vasc Surg 2002; 35: 368-375.
    CrossrefPubMedGoogle Scholar
  • 121 Xu Q. Biomechanical-stress-induced signalling and gene expression in the development of arteriosclerosis. Trends Cardiovasc Med 2000; 10: 35-41.
    CrossrefPubMedGoogle Scholar
  • 122 Srivastava PK, DeLeo AB, Old LJ. Tumor rejection antigens of chemically induced sarcomas of inbred mice. Proc Natl Acad Sci USA 1986; 83: 3407-3411.
    CrossrefPubMedGoogle Scholar
  • 123 Li Z, Menoret A, Srivastava P. Roles of heat-shock proteins in antigen presentation and cross-presentation. Curr Opin Immunol 2002; 14: 45-51.
    CrossrefPubMedGoogle Scholar
  • 124 Ishii T, Udono H, Yamano T. et al. Isolation of MHC class I-restricted tumor antigen peptide and its precursors associated with heat shock proteins hsp70, hsp90, and gp96. J Immunol 1999; 162: 1303-1309.
    PubMedGoogle Scholar
  • 125 Neuteboom W, Vis AA. The effects of low alcohol beers on the blood alcohol concentration. Blutalkohol 1991; 28: 393-396.
    PubMedGoogle Scholar
  • 126 Vabulas RM, Braedel S, Hilf N. et al. The endoplasmic reticulum-resident heat shock protein Gp96 activates dendritic cells via the Toll-like receptor 2/4 pathway. J Biol Chem 2002; 277: 20847-20853.
    CrossrefPubMedGoogle Scholar
  • 127 Bulut Y, Faure E, Thomas L. et al. Chlamydial heat shock protein 60 activates macrophages and endothelial cells through Toll-like receptor 4 and MD2 in a MyD88-dependent pathway. J Immunol 2002; 168: 1435-1440.
    CrossrefPubMedGoogle Scholar
  • 128 Vabulas RM, Ahmad-Nejad P, Ghose S. et al. HSP70 as endogenous stimulus of the Toll/interleukin-1 receptor signal pathway. J Biol Chem 2002; 277: 15107-15112.
    CrossrefPubMedGoogle Scholar
  • 129 Asea A, Kraeft SK, Kurt-Jones EA. et al. HSP70 stimulates cytokine production through a CD14-dependant pathway, demonstrating its dual role as a chaperone and cytokine. Nat Med 2000; 06: 435-442.
    CrossrefPubMedGoogle Scholar
  • 130 Flohe SB, Bruggemann J, Lendemans S. et al. Human heat shock protein 60 induces maturation of dendritic cells versus a Th1-promoting phenotype. J Immunol 2003; 170: 2340-2348.
    CrossrefPubMedGoogle Scholar
  • 131 Wu TC, Tanguay RM, Wu Y. et al. Presence of antibodies to heat stress proteins and its possible significance in workers exposed to high temperature and carbon monoxide. Biomed Environ Sci 1996; 09: 370-379.
    PubMedGoogle Scholar
  • 132 Xu Q, Willeit J, Marosi M. et al. Association of serum antibodies to heat-shock protein 65 with carotid atherosclerosis. Lancet 1993; 341: 255-259.
    CrossrefPubMedGoogle Scholar
  • 133 Xu Q, Kiechl S, Mayr M. et al. Association of serum antibodies to heat-shock protein 65 with carotid atherosclerosis : clinical significance determined in a follow-up study. Circulation 1999; 100: 1169-1174.
    CrossrefPubMedGoogle Scholar
  • 134 Huittinen T, Leinonen M, Tenkanen L. et al. Autoimmunity to human heat shock protein 60, Chlamydia pneumoniae infection, and inflammation in predicting coronary risk. Arterioscler Thromb Vasc Biol 2002; 22: 431-437.
    CrossrefPubMedGoogle Scholar
  • 135 Frostegard J, Lemne C, Andersson B. et al. Association of serum antibodies to heat-shock protein 65 with borderline hypertension. Hypertension 1997; 29: 40-44.
    CrossrefPubMedGoogle Scholar
  • 136 Birnie DH, Holme ER, McKay IC. et al. Association between antibodies to heat shock protein 65 and coronary atherosclerosis. Possible mechanism of action of Helicobacter pylori and other bacterial infections in increasing cardiovascular risk. Eur Heart J 1998; 19: 387-394.
    CrossrefPubMedGoogle Scholar
  • 137 Chan YC, Shukla N, Abdus-Samee M. et al. Anti-heat-shock protein 70 kDa antibodies in vascular patients. Eur J Vasc Endovasc Surg 1999; 18: 381-385.
    CrossrefPubMedGoogle Scholar
  • 138 Burian K, Kis Z, Virok D. et al. Independent and joint effects of antibodies to human heat-shock protein 60 and Chlamydia pneumoniae infection in the development of coronary atherosclerosis. Circulation 2001; 103: 1503-1508.
    CrossrefPubMedGoogle Scholar
  • 139 Gromadzka G, Zielinska J, Ryglewicz D. et al. Elevated levels of anti-heat shock protein antibodies in patients with cerebral ischaemia. Cerebrovasc Dis 2001; 12: 235-239.
    CrossrefPubMedGoogle Scholar
  • 140 Veres A, Fust G, Smieja M. et al. Relationship of anti-60 kDa heat shock protein and anti-cholesterol antibodies to cardiovascular events. Circulation 2002; 106: 2775-2780.
    CrossrefPubMedGoogle Scholar
  • 141 Kervinen H, Huittinen T, Vaarala O. et al. Antibodies to human heat shock protein 60, hypertension and dyslipidemia. A study of joint effects on coronary risk. Atherosclerosis 2003; 169: 339-344.
    CrossrefPubMedGoogle Scholar
  • 142 Zhu J, Katz RJ, Quyyumi AA. et al. Association of serum antibodies to heat-shock protein 65 with coronary calcification levels: suggestion of pathogentriggered autoimmunity in early atherosclerosis. Circulation 2004; 109: 36-41.
    CrossrefPubMedGoogle Scholar
  • 143 Zhang X, He MA, Cheng L. et al. Joint effects of antibody to heat shock protein 60, hypertension, and diabetes on risk of coronary heart disease in Chinese. Clin Chem 2008; 54: 1046-1052.
    CrossrefPubMedGoogle Scholar
  • 144 Shams S, Shafi S, Bodman-Smith K. et al. Anti-heat shock protein-27 (Hsp-27) antibody levels in patients with chest pain: association with established cardiovascular risk factors. Clin Chim Acta 2008; 395: 42-46.
    CrossrefPubMedGoogle Scholar
  • 145 Ghayour-Mobarhan M, Sahebkar A, Parizadeh SM. et al. Antibody titres to heat shock protein 27 are elevated in patients with acute coronary syndrome. Int J Exp Pathol 2008; 89: 209-215.
    CrossrefPubMedGoogle Scholar
  • 146 Burt D, Bruno G, Chaturvedi N. et al. Anti-heat shock protein 27 antibody levels and diabetes complications in the EURODIAB study. Diabetes Care 2009; 32: 1269-1271.
    CrossrefPubMedGoogle Scholar
  • 147 Burut DF, Borai A, Livingstone C. et al. Serum heat shock protein 27 antigen and antibody levels appear to be related to the macrovascular complications associated with insulin resistance: a pilot study. Cell Stress Chaperones 2010; 15: 379-386.
    CrossrefPubMedGoogle Scholar
  • 148 Azarpazhooh MR, Mobarra N, Parizadeh SM. et al. Serum high-sensitivity C-reactive protein and heat shock protein 27 antibody titers in patients with stroke and 6-month prognosis. Angiology 2010; 61: 607-612.
    CrossrefPubMedGoogle Scholar
  • 149 Pourghadamyari H, Moohebati M, Parizadeh SM. et al. Serum antibody titers against heat shock protein 27 are associated with the severity of coronary artery disease. Cell Stress Chaperones 2011; 16: 309-316.
    CrossrefPubMedGoogle Scholar
  • 150 Sahebkar A, Pourghadamyari H, Moohebati M. et al. A cross-sectional study of the association between heat shock protein 27 antibody titers, pro-oxidant-antioxidant balance and metabolic syndrome in patients with angiographically-defined coronary artery disease. Clin Biochem 2011; 44: 1390-1395.
    CrossrefPubMedGoogle Scholar
  • 151 Rahsepar AA, Mirzaee A, Moodi F. et al. Anti-Heat Shock Protein 27 Titers and Oxidative Stress Levels are Elevated in Patients With Valvular Heart Disease. Angiology. 2012 epub ahead of print
    PubMedGoogle Scholar
  • 152 Rahsepar AA, Mirzaee A, Moodi F. et al. Changes in anti-heat shock protein 27 antibody and C-reactive protein levels following cardiac surgery and their association with cardiac function in patients with cardiovascular disease. Cell Stress Chaperones. 2012 epub ahead of print
    PubMedGoogle Scholar
  • 153 Moohebati M, Bidmeshgi S, Azarpazhooh MR. et al. Simvastatin treatment reduces heat shock protein 60, 65, and 70 antibody titers in dyslipidemic patients: A randomized, double-blind, placebo-controlled, cross-over trial. Clin Biochem 2011; 44: 192-197.
    CrossrefPubMedGoogle Scholar
  • 154 Galli M. Clinical utility of laboratory tests used to identify antiphospholipid antibodies and to diagnose the antiphospholipid syndrome. Semin Thromb Hemost 2008; 34: 329-334.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 155 de Groot PG, Meijers JC. beta(2) -Glycoprotein I: evolution, structure and function. J Thromb Haemost 2011; 09: 1275-1284.
    CrossrefPubMedGoogle Scholar
  • 156 Matsuura E, Kobayashi K, Matsunami Y. et al. Autoimmunity, infectious immunity, and atherosclerosis. J Clin Immunol 2009; 29: 714-721.
    CrossrefPubMedGoogle Scholar
  • 157 Soltesz P, Veres K, Lakos G. et al. Evaluation of clinical and laboratory features of antiphospholipid syndrome: a retrospective study of 637 patients. Lupus 2003; 12: 302-307.
    CrossrefPubMedGoogle Scholar
  • 158 Koskenmies S, Vaarala O, Widen E. et al. The association of antibodies to cardiolipin, beta 2-glycoprotein I, prothrombin, and oxidized low-density lipoprotein with thrombosis in 292 patients with familial and sporadic systemic lupus erythematosus. Scand J Rheumatol 2004; 33: 246-252.
    CrossrefPubMedGoogle Scholar
  • 159 Lopez LR, Salazar-Paramo M, Palafox-Sanchez C. et al. Oxidized low-density lipoprotein and beta2-glycoprotein I in patients with systemic lupus erythematosus and increased carotid intima-media thickness: implications in autoimmune-mediated atherosclerosis. Lupus 2006; 15: 80-86.
    CrossrefPubMedGoogle Scholar
  • 160 Pereira I, Laurindo I, Burlingame R. et al. Auto-antibodies do not influence development of atherosclerotic plaques in rheumatoid arthritis. Joint Bone Spine 2008; 75: 416-421.
    CrossrefPubMedGoogle Scholar
  • 161 de Laat B, Pengo V, Pabinger I. et al. The association between circulating antibodies against domain I of beta2-glycoprotein I and thrombosis: an international multicenter study. J Thromb Haemost 2009; 07: 1767-1773.
    CrossrefPubMedGoogle Scholar
  • 162 Gustafsson J, Gunnarsson I, Borjesson O. et al. Predictors of the first cardiovascular event in patients with systemic lupus erythematosus - a prospective cohort study. Arthritis Res Ther 2009; 11: R186.
    CrossrefPubMedGoogle Scholar
  • 163 Gustafsson J, Simard JF, Gunnarsson I. et al. Risk factors for cardiovascular mortality in patients with systemic lupus erythematosus, a prospective cohort study. Arthritis Res Ther 2012; 14: R46.
    CrossrefPubMedGoogle Scholar
  • 164 Petri M. The lupus anticoagulant is a risk factor for myocardial infarction (but not atherosclerosis): Hopkins Lupus Cohort. Thromb Res 2004; 114: 593-595.
    CrossrefPubMedGoogle Scholar
  • 165 Petri M. Update on anti-phospholipid antibodies in SLE: the Hopkins’ Lupus Cohort. Lupus 2010; 19: 419-423.
    CrossrefPubMedGoogle Scholar
  • 166 Kiani AN, Post WS, Magder LS. et al. Predictors of progression in atherosclerosis over 2 years in systemic lupus erythematosus. Rheumatology 2011; 50: 2071-2079.
    CrossrefPubMedGoogle Scholar
  • 167 Pahor A, Hojs R, Holc I. et al. Antiphospholipid antibodies as a possible risk factor for atherosclerosis in patients with rheumatoid arthritis. Immunobiology 2006; 211: 689-694.
    CrossrefPubMedGoogle Scholar
  • 168 Holc I, Hojs R, Cikes N. et al. Antiphospholipid antibodies and atherosclerosis: insights from rheumatoid arthritis--a five-year follow-up study. Immunobiology 2011; 216: 1331-1337.
    CrossrefPubMedGoogle Scholar
  • 169 Artenjak A, Lakota K, Frank M. et al. Antiphospholipid antibodies as nontraditional risk factors in atherosclerosis based cardiovascular diseases without overt autoimmunity. A critical updated review. Autoimmun Rev 2012; 11: 873-882.
    CrossrefPubMedGoogle Scholar
  • 170 Brey RL, Abbott RD, Curb JD. et al. beta(2)-Glycoprotein 1-dependent anticardiolipin antibodies and risk of ischaemic stroke and myocardial infarction: the honolulu heart program. Stroke 2001; 32: 1701-1706.
    CrossrefPubMedGoogle Scholar
  • 171 Faria-Neto JR, Chyu KY, Li X. et al. Passive immunisation with monoclonal IgM antibodies against phosphorylcholine reduces accelerated vein graft atherosclerosis in apolipoprotein E-null mice. Atherosclerosis 2006; 189: 83-90.
    CrossrefPubMedGoogle Scholar
  • 172 Palinski W, Hörkkö S, Miller E. 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.
    CrossrefPubMedGoogle Scholar