A relationship between serological markers of chronic C. pneumoniae and CMV infection and hsp60 in patients with atherosclerotic carotid stenosis
Languages of publication
A number of epidemiological studies conducted over the last decade indicate a relationship between specific pathogen infections and the development of atherosclerosis, although no pathogenetic pathways connecting these two have been determined. Recent reports support the role of heat shock proteins (HSPs) in atherogenesis. The HSPs are also believed to be a link between the infection and the development of atherosclerotic lesions. The aims of study: Immunohistochemical evaluation of carotid artery segments to show the relationship between the presence of heat shock proteins and the serum levels of anti-hsp60 antibodies. An attempt to demonstrate a relationship between an expression of chronic C. pneumoniae and CMV antigens. Material and Methods: The study included 41 patients qualified for carotid artery endarterectomy and 18 healthy volunteers of corresponding age. Levels of anti- hsp60, anti-C. pneumoniae IgA and IgG, anti-CMV IgG antibodies as well as hsCRP were determined. Results: The mean serum levels of anti-hsp60 antibodies were higher in patients with advanced atherosclerosis as compared to healthy volunteers (55.3±64.1 vs 32.8±29.8; p < 0.05). There was a strong correlation between anti-hsp60 antibodies and the expression of hsp60 in carotid arterial wall, as confirmed by immunohistochemical evaluation. The study group showed statistically significant higher levels of hsCRP. Furthermore, statistically significant higher serum levels of anti-C. pneumoniae IgG and IgA as well as anti-CMV IgG antibodies were found in the study group as compared to controls. No correlation was shown between the markers of chronic infection induced by the tested pathogens and serum levels of anti-HSP and hsCRP. Conclusions: Higher protein expression in vascular walls is closely correlated with the level of anti-hsp60. At the same time, no significant relationship between anti-hsp60 antibodies and serological markers of infection was observed, which may only indicate an indirect role of infection in the assessment of breaking the immunological tolerance against autologous HSPs.
- Almanzar G1, Öllinger R, Leuenberger J, Onestingel E, Rantner B, Zehm S, Cardini B, van der Zee R, Grundtman C, Wick G (2012) Autoreactive HSP60 epitope-specific T-cells in early human atherosclerotic lesions. J Autoimmun 39: 441-450.
- Apfalter P (2006) Chlamydia pneumoniae, stroke, and serological associations: anything learned from the atherosclerosis-cardiovascular literature or do we have to start over again? Stroke 37: 756-758.
- Bason C, Corrocher R, Lunardi C, Puccetti P, Olivieri O, Girelli D, Navone R, Beri R, Millo E, Margonato A, Martinelli N, Puccetti A (2003) Interaction of antibodies against cytomegalovirus with heat-shock protein 60 in pathogenesis of atherosclerosis. Lancet 362: 1971-1977.
- Benagiano M, D'Elios MM, Amedei A, Azzurri A, van der Zee R, Ciervo A, Rombolà G, Romagnani S, Cassone A, Del Prete G (2005) Human 60-kDa heat shock protein is a target autoantigen of T cells derived from atherosclerotic plaques. J Immunol 174: 6509-6517.
- Cuffini C, Alberto Guzmán L, Villegas N, Eduardo Alonso C, Martínez-Riera L, Rodríguez-Fermepín M, Carolina Entrocassi A, Pilar Adamo M, Pedranti M, Zapata M (2006) Isolation of Chlamydophila pneumoniae from atheromas of the carotid artery and their antibiotics susceptibility profile. Enferm Infecc Microbiol Clin 24: 81-85.
- Drożdż W, Zawilińska B, Wysocki A, Kleszcz E, Wilczek M (2003) Chlamydia pneumoniae in patients with atherosclerotic ischemia of the lower limbs. Przegl Lek 60 (Suppl 7): 53-55.
- Fichtlscherer S, Rosenberger G, Walter DH, Breuer S, Dimmeler S, Zeiher AM (2000) Elevated C-reactive protein levels and impaired endothelial vasoreactivity in patients with coronary artery disease. Circulation 102: 1000-1006.
- Fong IW (2000) Antibiotics effects in a rabbit model of Chlamydia pneumoniae-induced atherosclerosis. J Infect Dis 181 (Suppl 3): S514-S518.
- Grayston JT, Kronmal RA, Jackson LA, Parisi AF, Muhlestein JB, Cohen JD, Rogers WJ, Crouse JR, Borrowdale SL, Schron E, Knirsch C, ACES Investigators (2005) Azithromycin for the secondary prevention of coronary events. N Engl J Med 352: 1637-1645.
- Grayston JT (2000) Background and current knowledge of Chlamydia pneumoniae and atherosclerosis. J Infect Dis 181 Suppl 3: S402-S410.
- Gromadzka G, Zielinska J, Ryglewicz D, Fiszer U, Czlonkowska A (2001) Elevated levels of anti-heat shock protein antibodies in patients with cerebral ischemia. Cerebrovasc Dis 12: 235-239.
- Gurfinkel E, Bozovich G, Beck E, Testa E, Livellara B, Mautner B (1999) Treatment with the antibiotic roxithromycin in patients with acute non-Q-wave coronary syndromes. The final report of the ROXIS Study. Eur Heart J 20: 121-127.
- Haider AW, Wilson PW, Larson MG, Evans JC, Michelson EL, Wolf PA, O'Donnell CJ, Levy D (2002) The association of seropositivity to Helicobacter pylori, Chlamydia pneumoniae, and cytomegalovirus with risk of cardiovascular disease: a prospective study. J Am Coll Cardiol 40: 1408-1413.
- Ieven MM, Hoymans VY (2005) Involvement of Chlamydia pneumoniae in atherosclerosis: more evidence for lack of evidence. J Clin Microbiol 43: 19-24.
- Janczak D, Skora J, Pupka A, Patrzalek D, Korta K, Pawlowski S, Rucinski A, Szyber P (2004) The presence of Chlamydia pneumoniae in carotid artery. Pol Merkur Lekarski 16: 513-515 (in Polish).
- Kaklikkaya I, Kaklikkaya N, Buruk K, Pulathan Z, Koramaz I, Aydin F, Tosun I, Osman Kilic A, Ozcan F (2006) Investigation of Chlamydia pneumoniae DNA, chlamydial lipopolisaccharide antigens, and Helicobacter pylori DNA in atherosclerotic plaques of patients with aortoiliac occlusive disease. Cardiovasc Pathol 15: 105-109.
- Kazmierski R, Kozubski W (2002) The influence of the Chlamydia pneumoniae infection on the development of cerebral atherosclerosis. Neurol Neurochir Pol 36: 131-142 (in Polish).
- Kilic A1, Mandal K (2012) Heat shock proteins: pathogenic role in atherosclerosis and potential therapeutic implications. Autoimmune Dis 2012: 502813.
- Kol A, Sukhova GK, Lichtman AH, Libby P (1998) Chlamydial heat shock protein 60 localizes in human atheroma and regulates macrophage tumor necrosis factor-α and matrix metalloproteinase expresion. Circulation 98: 300-307.
- Lamb DJ, El-Sankary W, Ferns GA (2003) Molecular mimicry in atherosclerosis: a role for heat shock proteins in immunisation. Atherosclerosis 167: 177-185.
- Macario AJ, Cappello F, Zummo G, Conway de Macario E (2010) Chaperonopathies of senescence and the scrambling of interactions between the chaperoning and the immune systems. Ann N Y Acad Sci 1197: 85-93.
- Mandal K, Foteinos G, Jahangiri M, Xu Q (2005) Role of antiheat shock protein 60 autoantibodies in atherosclerosis. Lupus 14: 742-746.
- Mandal K, Jahangiri M, Xu Q (2004) Autoimmunity to heat shock proteins in atherosclerosis. Autoimmun Rev 3: 31-37.
- Maron R, Sukhova G, Faria AM, Hoffmann E, Mach F, Libby P, Weiner HL (2002) Mucosal administration of heat shock protein-65 decreases atherosclerosis and inflammation in aortic arch of low-density lipoprotein receptor-deficient mice. Circulation 106: 1708-1715.
- Mayr M, Metzler B, Kiechl S, Willeit J, Schett G, Xu Q, Wick G (1999) Endothelial cytotoxicity mediated by serum antibodies to heat shock proteins of Escherichia coli and Chlamydia pneumoniae. Immune reactions to heat shock proteins as a possible link between infection and atherosclerosis. Circulation 99: 1560-1566.
- Mosorin M, Surcel HM, Laurila A, Lehtinen M, Karttunen R, Juvonen J, Paavonen J, Morrison RP, Saikku P, Juvonen T (2000) Detection of Chlamydia pneumoniae-reactive T lymphocytes in human atherosclerotic plaques of carotid artery. Arterioscler Thromb Vasc Biol 20: 1061-1067.
- Muhlestein JB, Anderson JL, Carlquist JF, Salunkhe K, Horne BD, Pearson RR, Bunch TJ, Allen A, Trehan S, Nielson C (2000) Randomized secondary prevention trial of azithromycin in patients with coronary artery disease: primary clinical results of the ACADEMIC study. Circulation 102: 1755-1760.
- Mussa FF, Chai H, Wang X, Yao Q, Lumsden AB, Chen C (2006) Chlamydia pneumoniae and vascular disease: an update. J Vasc Surg 43: 1301-1307.
- O'Connor CM, Dunne MW, Pfeffer MA, Muhlestein JB, Yao L, Gupta S, Benner RJ, Fisher MR, Cook TD (2003) Investigators in the WIZARD Study: Azithromycin for the secondary prevention of coronary heart disease events: the WIZARD study: a randomized controlled trial. JAMA 290: 1459-1466.
- Pfister G, Stroh CM, Perschinka H, Kind M, Knoflach M, Hinterdorfer P, Wick G (2005) Detection of HSP60 on the membrane surface of stressed human endothelial cells by atomic force and confocal microscopy. J Cell Sci 118: 1587-1594.
- Rabczyński M, Fiodorenko-Dumas Ż, Adamiec R, Paprocka-Borowicz M, Dumas I (2012) Role of anti-HSP 60/65 antibodies in atherogenesis in patients with type 2 diabetes and lower limb ischemia. J Physiol Pharmacol 63: 691-696.
- Sessa R, Di Pietro M, Schiavoni G, Galdiero M, Cipriani P, Romano S, Zagaglia C, Santino I, Faccilongo S, Del Piano M (2006) Chlamydia pneumoniae in asymptomatic carotid atherosclerosis. Int J Immunopathol Pharmacol 19: 111-118.
- Tarnacka B, Gromadzka G, Czlonkowska A (2002) Increased circulating immune complexes in acute stroke: the triggering role of Chlamydia pneumoniae and cytomegalovirus. Stroke 33: 936-940.
- Veres A, Prohászka Z, Kilpinen S, Singh M, Füst G, Hurme M (2002) The promoter polymorphism of the IL-6 gene is associated with levels of antibodies to 60-kDa heat-shock proteins. Immunogenetics 53: 851-856.
- Wick G, Knoflach M, Xu Q (2004) Autoimmune and inflammatory mechanisms in atherosclerosis. Annu Rev Immunol 22: 361-403.
- Wick G, Schett G, Amberger A, Kleindienst R, Xu Q (1995) Is atherosclerosis an immunologically mediated disease? Immunol Today 16: 27-33.
- Wiesli P, Czerwenka W, Meniconi A, Maly FE, Hoffmann U, Vetter W, Schulthess G (2002) Roxithromycin treatment prevents progression of peripheral arterial occlusive disease in Chlamydia pneumoniae seropositive men: a randomized, double-blind, placebo-controlled trial. Circulation 105: 2646-2652.
- Xu Q, Dietrich H, Steiner HJ, Gown AM, Schoel B, Mikuz G, Kaufmann SH, Wick G (1992) Induction of arteriosclerosis in normocholesterolemic rabbits by immunisation with heat shock protein 65. Arterioscler Thromb 12: 789-799.
- Xu Q, Schett G, Perschinka H, Mayr M, Egger G, Oberhollenzer F, Willeit J, Kiechl S, Wick G (2000) Serum soluble heat shock protein 60 is elevated in subjects with atherosclerosis in a general population. Circulation 102: 14-20.
- Xu Q, Willeit J, Marosi M, Kleindienst R, Oberhollenzer F, Kiechl S, Stulnig T, Luef G, Wick G (1993) Association of serum antibodies to heat shock proteins 65 with carotid atherosclerosis. Lancet 341: 255-259.
Publication order reference