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Influence of intimal Chlamydophila pneumoniae persistence on cardiovascular complications after coronary intervention

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Abstract

Purpose

Chlamydophila pneumoniae has been implicated in atherosclerosis/restenosis; however, clear evidence is missing. Therefore, the aim of our study was to examine the influence of intimal infection and systemic inflammation on cardiovascular complications after coronary intervention.

Methods

45 atheroma specimens from patients with symptomatic coronary artery disease who underwent directional endatherectomy with stent implantation were analyzed by immunohistochemistry to detect chlamydial (c) and human (h) heat shock protein (HSP) 60. The antibodies used against cHSP60 and hHSP60 were characterized by specificity and lack of cross immunoreactivity. In addition, serum Ig antibodies against Chlamydophila pneumoniae and against mycobacterial (m) HSP65 as well as serum CRP levels were measured. At follow-up of 6 months, quantitative coronary angiography was performed and major adverse cardiac events (MACE) were assessed.

Results

Atheroma specimens of all 10 patients with MACE were positive for cHSP60 with overall higher cHSP60 tissue expressions (1.1 ± 0.4 %) and serum CRP levels (2.18 ± 0.85 mg/dl) compared to the remaining 35 patients without MACE (7 of 35 specimens positive for cHSP60, mean cHSP60 expression: 0.4 ± 0.1 %, CRP levels: 0.67 ± 0.16 mg/dl, p < 0.05). Colocalization of both HSP60 homologues was more frequent in the MACE group. Anti-mHSP65 serum titers were significantly higher in MACE (1:510) versus non-MACE patients (1:335) and correlated positively with plaque expressions of cHSP60 and hHSP60 (r = 0.54, p < 0.05; r = 0.46, p < 0.05; resp.).

Conclusions

Intimal presence of cHSP60, systemic CRP and antibodies against mHSP65 are predictors for occurrence of MACE after coronary intervention.

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References

  1. Ross R. Atherosclerosis—an inflammatory disease. N Engl J Med. 1999;340:115–26.

    Article  CAS  PubMed  Google Scholar 

  2. Elkind MS, Luna JM, Moon YP, Boden-Albala B, Liu KM, Spitalnik S, Rundek T, Sacco RL, Paik MC. Infectious burden and carotid plaque thickness: the northern Manhattan study. Stroke. 2010;41:e117–22.

    Article  PubMed Central  PubMed  Google Scholar 

  3. Andrié RP, Bauriedel G, Tuleta I, Braun P, Nickenig G, Skowasch D. Impact of intimal pathogen burden in acute coronary syndromes—correlation with inflammation, thrombosis, and autoimmunity. Cardiovasc Pathol. 2010;19:e205–10.

    Article  PubMed  Google Scholar 

  4. Corrado E, Novo S. Role of inflammation and infection in vascular disease. Acta Chir Belg. 2005;105:567–79.

    CAS  PubMed  Google Scholar 

  5. Rahel BM, Visseren FL, Suttorp MJ, Plokker TH, Kelder JC, de Jongh BM, Diepersloot RJ, Verkooyen RP, Bouter KP. Cytomegalovirus and Chlamydia pneumoniae as predictors for adverse events and angina pectoris after percutaneous coronary intervention. Am Heart J. 2004;148:670–5.

    Article  PubMed  Google Scholar 

  6. Elkind MS. Infectious burden: a new risk factor and treatment target for atherosclerosis. Infect Disord Drug Targets. 2010;10:84–90.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Fazio G, Giovino M, Gullotti A, Bacarella D, Novo G, Novo S. Atherosclerosis, inflammation and Chlamydia pneumoniae. World J Cardiol. 2009;1:31–40.

    Article  PubMed Central  PubMed  Google Scholar 

  8. Kaufmann SH, Schoel B, van Embden JD, Koga T, Wand-Württenberger A, Munk ME, Steinhoff U. Heat-shock protein 60: implications for pathogenesis of and protection against bacterial infections. Immunol Rev. 1991;121:67–90.

    Article  CAS  PubMed  Google Scholar 

  9. Andrie RP, Bauriedel G, Braun P, Höpp HW, Nickenig G, Skowasch D. Prevalence of intimal heat shock protein 60 homologues in unstable angina and correlation with anti-heat shock protein antibody titers. Basic Res Cardiol. 2011;106:657–65.

    Article  CAS  PubMed  Google Scholar 

  10. Mayr M, Metzler B, Kiechl S, Willeit J, Schett G, Xu Q, Wick G. 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. 1999;99:1560–6.

    Article  CAS  PubMed  Google Scholar 

  11. Schumacher A, Lerkerød AB, Seljeflot I, Sommervoll L, Holme I, Otterstad JE, Arnesen H. Chlamydia pneumoniae serology: importance of methodology in patients with coronary heart disease and healthy individuals. J Clin Microbiol. 2001;39:1859–64.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Zebrack JS, Anderson JL. The role of infection in the pathogenesis of cardiovascular disease. Prog Cardiovasc Nurs. 2003;18:42–9.

    Article  PubMed  Google Scholar 

  13. Jahromi BS, Hill MD, Holmes K, Hutchison S, Tucker WS, Chiu B. Chlamydia pneumoniae and atherosclerosis following carotid endarterectomy. Can J Neurol Sci. 2003;30:333–9.

    Article  PubMed  Google Scholar 

  14. Kannengiesser M, Kaltenbach M, Stille W, Reifart N, Haase J. Influence of doxycycline on clinical and angiographic outcome following percutaneous coronary intervention. J Interv Cardiol. 2004;17:447–53.

    Article  PubMed  Google Scholar 

  15. Yuan Y, Lyng K, Zhang YX, Rockey DD, Morrison RP. Monoclonal antibodies define genus-specific, species-specific, and cross-reactive epitopes of the chlamydial 60-kilodalton heat shock protein (hsp60): specific immunodetection and purification of chlamydial hsp60. Infect Immun. 1992;60:2288–96.

    CAS  PubMed Central  PubMed  Google Scholar 

  16. Boog CJ1, de Graeff-Meeder ER, Lucassen MA, van der Zee R, Voorhorst-Ogink MM, van Kooten PJ, Geuze HJ, van Eden W. Two monoclonal antibodies generated against human hsp60 show reactivity with synovial membranes of patients with juvenile chronic arthritis. J Exp Med. 1992;175:1805–10.

  17. Tuleta I, Skowasch D, Peuster M, Nickenig G, Bauriedel G. Cells of primarily extravascular origin in neointima formation following stent implantation: coordinated expression of endothelial progenitor, dendritic and neural crest-derived cells. Cardiology. 2008;110:199–205.

    Article  PubMed  Google Scholar 

  18. Skowasch D, Jabs A, Andrié R, Dinkelbach S, Schiele TM, Wernert N, Lüderitz B, Bauriedel G. Pathogen burden, inflammation, proliferation and apoptosis in human in-stent restenosis. Tissue characteristics compared to primary atherosclerosis. J Vasc Res. 2004;41:525–34.

    Article  PubMed  Google Scholar 

  19. Fong IW, Chiu B, Viira E, Tucker W, Wood H, Peeling RW. Chlamydial heat-shock protein-60 antibody and correlation with Chlamydia pneumoniae in atherosclerotic plaques. J Infect Dis. 2002;186:1469–73.

    Article  CAS  PubMed  Google Scholar 

  20. Schiele F, Batur MK, Seronde MF, Meneveau N, Sewoke P, Bassignot A, Couetdic G, Caulfield F, Bassand JP. Cytomegalovirus, Chlamydia pneumoniae, and Helicobacter pylori IgG antibodies and restenosis after stent implantation: an angiographic and intravascular ultrasound study. Heart Vessels. 2002;16:137–45.

    Article  Google Scholar 

  21. Carlsson J, Miketic S, Brom J, Ross R, Bachmann H, Tebbe U. Prior cytomegalovirus, Chlamydia pneumoniae or Helicobacter pylori infection and the risk of restenosis after percutaneous transluminal coronary angioplasty. Int J Cardiol. 2000;73:165–71.

    Article  CAS  PubMed  Google Scholar 

  22. Borel N, Summersgill JT, Mukhopadhyay S, Miller RD, Ramirez JA, Pospischil A. Evidence for persistent Chlamydia pneumoniae infection of human coronary atheromas. Atherosclerosis. 2008;199:154–61.

    Article  CAS  PubMed  Google Scholar 

  23. Fagerberg B, Gnarpe J, Gnarpe H, Agewall S, Wikstrand J. Chlamydia pneumoniae but not cytomegalovirus antibodies are associated with future risk of stroke and cardiovascular disease: a prospective study in middle-aged to elderly men with treated hypertension. Stroke. 1999;30:299–305.

    Article  CAS  PubMed  Google Scholar 

  24. Hayashida K, Tanaka M, Morita H, Hayashi F, Inada T, Suzuki H, Sakamoto T, Katsuragawa M, Hibino H, Kambara H. Chlamydia pneumoniae seropositivity predicts the risk of restenosis after percutaneous transluminal coronary angioplasty. Am Heart J. 2002;144:491–500.

    Article  Google Scholar 

  25. Blessing E, Campbell LA, Rosenfeld ME, Kuo CC. Chlamydia pneumoniae and hyperlipidemia are co-risk factors for atherosclerosis: infection prior to induction of hyperlipidemia does not accelerate development of atherosclerotic lesions in C57BL/6J mice. Infect Immun. 2002;70:5332–4.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  26. Li L, Messas E, Batista EL Jr, Levine RA, Amar S. Porphyromonas gingivalis infection accelerates the progression of atherosclerosis in a heterozygous apolipoprotein E-deficient murine model. Circulation. 2002;105:861–7.

    Article  PubMed  Google Scholar 

  27. Hu H, Pierce GN, Zhong G. The atherogenic effects of chlamydia are dependent on serum cholesterol and specific to Chlamydia pneumoniae. J Clin Investig. 1999;103:747–53.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. Lin FY, Lin YW, Huang CY, Chang YJ, Tsao NW, Chang NC, Ou KL, Chen TL, Shih CM, Chen YH. GroEL1, a heat shock protein 60 of Chlamydia pneumoniae, induces lectin-like oxidized low-density lipoprotein receptor 1 expression in endothelial cells and enhances atherogenesis in hypercholesterolemic rabbits. J Immunol. 2011;186:4405–14.

    Article  CAS  PubMed  Google Scholar 

  29. Horne BD, Muhlestein JB, Strobel GG, Carlquist JF, Bair TL, Anderson JL, Intermountain Heart Collaborative (IHC) Study Group. Greater pathogen burden but not elevated C-reactive protein increases the risk of clinical restenosis after percutaneous coronary intervention. Am Heart J. 2002;144:491–500.

    Article  PubMed  Google Scholar 

  30. Kol A, Sukhova GK, Lichtman AH, Libby P. Chlamydial heat shock protein 60 localizes in human atheroma and regulates macrophage tumor necrosis factor-α and matrix metalloproteinase expression. Circulation. 1998;98:300–7.

    Article  CAS  PubMed  Google Scholar 

  31. Kol A, Bourcier T, Lichtman AH, Libby P. Chlamydial and human heat shock protein 60 s activate human vascular endothelium, smooth muscle cells, and macrophages. J Clin Investig. 1999;103:571–7.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. Zhang Y, Xiong Q, Hu X, Sun Y, Tan X, Zhang H, Lu Y, Liu J. A novel atherogenic epitope from Mycobacterium tuberculosis heat shock protein 65 enhances atherosclerosis in rabbit and LDL receptor-deficient mice. Heart Vessels. 2012;27:411–8.

    Article  PubMed  Google Scholar 

  33. Jousilahti P, Salomaa V, Rasi V, Vahtera E, Palosuo T. The association of c-reactive protein, serum amyloid a and fibrinogen with prevalent coronary heart disease—baseline findings of the PAIS project. Atherosclerosis. 2001;156:451–6.

    Article  CAS  PubMed  Google Scholar 

  34. Ridker PM, Hennekens CH, Buring JE, Rifai N. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med. 2000;342:836–43.

    Article  CAS  PubMed  Google Scholar 

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Conflict of interest

On behalf of all the authors, the corresponding author states that there is no conflict of interest.

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Authors and Affiliations

  1. Department of Internal Medicine II, Cardiology and Pulmonology, University of Bonn, Bonn, Germany

    I. Tuleta, D. Reek, G. Nickenig, D. Skowasch & R. Andrié

  2. Department of Cardiology, Heart Center Duisburg, Duisburg, Germany

    P. Braun

  3. Department of Cardiology, Hospital of Schmalkalden, Schmalkalden, Germany

    G. Bauriedel

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  1. I. Tuleta
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  2. D. Reek
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  3. P. Braun
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  4. G. Bauriedel
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  5. G. Nickenig
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  6. D. Skowasch
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  7. R. Andrié
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Correspondence to I. Tuleta.

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Tuleta, I., Reek, D., Braun, P. et al. Influence of intimal Chlamydophila pneumoniae persistence on cardiovascular complications after coronary intervention. Infection 43, 51–57 (2015). https://doi.org/10.1007/s15010-014-0694-1

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  • DOI: https://doi.org/10.1007/s15010-014-0694-1

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