Journal of Vascular Surgery
Volume 43, Issue 6 , Pages 1301-1307 , June 2006

Chlamydia pneumoniae and vascular disease: An update

  • Firas F. Mussa, MD

      Affiliations

    • Molecular Surgeon Research Center, Division of Vascular Surgery and Endovascular Therapy, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas
    • ,
  • Hong Chai, MD, PhD

      Affiliations

    • Molecular Surgeon Research Center, Division of Vascular Surgery and Endovascular Therapy, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas
    • ,
  • Xinwen Wang, MD, PhD

      Affiliations

    • Molecular Surgeon Research Center, Division of Vascular Surgery and Endovascular Therapy, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas
    • ,
  • Qizhi Yao, MD, PhD

      Affiliations

    • Molecular Surgeon Research Center, Division of Vascular Surgery and Endovascular Therapy, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas
    • ,
  • Alan B. Lumsden, MD

      Affiliations

    • Molecular Surgeon Research Center, Division of Vascular Surgery and Endovascular Therapy, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas
    • Texas Heart Institute at St Luke’s Episcopal Hospital, Houston, Texas
    • ,
  • Changyi Chen, MD, PhD

      Affiliations

    • Molecular Surgeon Research Center, Division of Vascular Surgery and Endovascular Therapy, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas
    • Corresponding Author InformationReprint requests: Changyi (Johnny) Chen, MD, PhD, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, One Baylor Plaza, Mail Stop: NAB-2010 Houston, TX 77030

Received 16 January 2006 ,Accepted 26 February 2006.

References 

  1. Ross R . Atherosclerosis—an inflammatory disease . N Engl J Med . 1999;340:115–126
  2. Grayston JT . Background and current knowledge of Chlamydia pneumoniae and atherosclerosis . J Infect Dis . 2000;181(Suppl 3):S402–S410
  3. Grayston JT , Kuo CC , Wang SP , Altman J . A new Chlamydia psittaci strain, TWAR, isolated in acute respiratory tract infections . N Engl J Med . 1986;315:161–168
  4. Saikku P , Leinonen M , Mattila K , Ekman MR , Nieminen MS , Makela PH , et al.   Serological evidence of an association of a novel Chlamydia, TWAR, with chronic coronary heart disease and acute myocardial infarction . Lancet . 1988;2:983–986
  5. Sessa R , Di Pietro M , Schiavoni G , Santino I , Benedetti-Valentini F , Perna R , et al.   Chlamydia pneumoniae DNA in patients with symptomatic carotid atherosclerotic disease . J Vasc Surg . 2003;37:1027–1031
  6. Grayston JT , Kuo CC , Coulson AS , Campbell LA , Lawrence RD , Lee MJ , et al.   Chlamydia pneumoniae (TWAR) in atherosclerosis of the carotid artery . Circulation . 1995;92:3397–3400
  7. Kuo CC , Gown AM , Benditt EP , Grayston JT . Detection of Chlamydia pneumoniae in aortic lesions of atherosclerosis by immunocytochemical stain . Arterioscler Thromb . 1993;13:1501–1504
  8. Kuo CC , Coulson AS , Campbell LA , Cappuccio AL , Lawrence RD , Wang SP , et al.   Detection of Chlamydia pneumoniae in atherosclerotic plaques in the walls of arteries of lower extremities from patients undergoing bypass operation for arterial obstruction . J Vasc Surg . 1997;26:29–31
  9. Grayston JT , Campbell LA , Kuo CC , Mordhorst CH , Saikku P , Thom DH , et al.   A new respiratory tract pathogen (Chlamydia pneumoniae strain TWAR) . J Infect Dis . 1990;161:618–625
  10. Saikku P , Leinonen M , Tenkanen L , Linnanmaki E , Ekman MR , Manninen V , et al.   Chronic Chlamydia pneumoniae infection as a risk factor for coronary heart disease in the Helsinki Heart Study . Ann Intern Med . 1992;116:273–278
  11. Kuo CC , Grayston JT , Campbell LA , et al.   Chlamydia pneumoniae (TWAR) in coronary arteries of young adults (15-34 years old) . Proc Natl Acad Sci U S A . 1995;92:6911–6914
  12. Kuo CC , Shor A , Campbell LA , Goo YA , Wissler RW , Benditt EP , et al.   Demonstration of Chlamydia pneumoniae in atherosclerotic lesions of coronary arteries . J Infect Dis . 1993;167:841–849
  13. Shi Y , Tokunaga O . Chlamydia pneumoniae and multiple infections in the aorta contribute to atherosclerosis . Pathol Int . 2002;52:755–763
  14. Ramirez JA . Isolation of Chlamydia pneumoniae from the coronary artery of a patient with coronary atherosclerosis. The Chlamydia pneumoniae/Atherosclerosis Study Group . Ann Intern Med . 1996;125:979–982
  15. Beatty WL , Morrison RP , Byrne GI . Persistent chlamydiae (from cell culture to a paradigm for Chlamydial pathogenesis) . Microbiol Rev . 1994;58:686–699
  16. 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
  17. Muhlestein JB , Hammond EH , Carlquist JF , Radicke E , Thomson MJ , Karagounis LA , et al.   Increased incidence of Chlamydia species within the coronary arteries of patients with symptomatic atherosclerotic versus other forms of cardiovascular disease . J Am Coll Cardiol . 1996;27:1555–1561
  18. Arcari CM , Gaydos CA , Nieto FJ , Krauss M , Nelson KE , et al.   Association between Chlamydia pneumoniae and acute myocardial infarction in young men in the United States military (the importance of timing of exposure measurement) . Clin Infect Dis . 2005;40:1123–1130
  19. Mayr M , Metzler B , Kiechl S , Willeit J , Schett G , Xu Q , et al.   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;99:1560–1566
  20. Ciervo A , Visca P , Petrucca A , Biasucci LM , Maseri A , Cassone A , et al.   Antibodies to 60-kilodalton heat shock protein and outer membrane protein 2 of Chlamydia pneumoniae in patients with coronary heart disease . Clin Diagn Lab Immunol . 2002;9:66–74
  21. 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;186:1469–1473
  22. Huittinen T , Leinonen M , Tenkanen L , Manttari M , Virkkunen H , Pithanen T . Autoimmunity to human heat shock protein 60, Chlamydia pneumoniae infection, and inflammation in predicting coronary risk . Arterioscler Thromb Vasc Biol . 2002;22:431–437
  23. Mahdi OS , Horne BD , Mullen K , Muhlestein JB , Byrne GI . Serum immunoglobulin G antibodies to chlamydial heat shock protein 60 but not to human and bacterial homologs are associated with coronary artery disease . Circulation . 2002;106:1659–1663
  24. Biasucci LM , Liuzzo G , Ciervo A , Pertucca A , Piro M , Angiolillo DJ , et al.   Antibody response to chlamydial heat shock protein 60 is strongly associated with acute coronary syndromes . Circulation . 2003;107:3015–3017
  25. Johnston SC , Messina LM , Browner WS , Lawton MT , Morris C , Dean C . C-reactive protein levels and viable Chlamydia pneumoniae in carotid artery atherosclerosis . Stroke . 2001;32:2748–2752
  26. Mayr M , Kiechl S , Willeit J , Wick G , Xu Q . Infections, immunity, and atherosclerosis (associations of antibodies to Chlamydia pneumoniae, Helicobacter pylori, and cytomegalovirus with immune reactions to heat-shock protein 60 and carotid or femoral atherosclerosis) . Circulation . 2000;102:833–839
  27. LaBiche R , Koziol D , Quinn TC , Gaydos C , Azhar S , Ketron G . Presence of Chlamydia pneumoniae in human symptomatic and asymptomatic carotid atherosclerotic plaque . Stroke . 2001;32:855–860
  28. Lindholt JS , Ashton HA , Scott RA . Indicators of infection with Chlamydia pneumoniae are associated with expansion of abdominal aortic aneurysms . J Vasc Surg . 2001;34:212–215
  29. Vammen S , Lindholt JS , Andersen PL , Henneberg EW , Ostergaard L . Antibodies against Chlamydia pneumoniae predict the need for elective surgical intervention on small abdominal aortic aneurysms . Eur J Vasc Endovasc Surg . 2001;22:165–168
  30. Maraha B , den Heijer M , Kluytmans J , Peeters M . Impact of serological methodology on assessment of the link between Chlamydia pneumoniae and vascular diseases . Clin Diagn Lab Immunol . 2004;11:789–791
  31. Lindholt JS , Stovring J , Ostergaard L , Urbonavicius S , Henneberg EW , Honore B , et al.   Serum antibodies against Chlamydia pneumoniae outer membrane protein cross-react with the heavy chain of immunoglobulin in the wall of abdominal aortic aneurysms . Circulation . 2004;109:2097–2102
  32. Cheuk BL , Ting AC , Cheng SW . Detection of C pneumoniae by polymerase chain reaction-enzyme immunoassay in abdominal aortic aneurysm walls and its association with rupture . Eur J Vasc Endovasc Surg . 2005;29:150–155
  33. Blasi F , Denti F , Erba M , Cosentini R , Racanelli R , Rinaldi A , et al.   Detection of Chlamydia pneumoniae but not Helicobacter pylori in atherosclerotic plaques of aortic aneurysms . J Clin Microbiol . 1996;34:2766–2769
  34. Vammen S , Vorum H , Ostergaard L , Henneberg EW , Lindholt JS . Immunoblotting analysis of abdominal aortic aneurysms using antibodies against Chlamydia pneumoniae recombinant MOMP . Eur J Vasc Endovasc Surg . 2002;24:81–85
  35. Wiesli P , Czerwenka W , Meniconi A , Maly FE , Hoffman U , Vetter W , et al.   Roxithromycin treatment prevents progression of peripheral arterial occlusive disease in Chlamydia pneumoniae seropositive men (a randomized, double-blind, placebo-controlled trial) . Circulation . 2002;105:2646–2652
  36. Muhlestein JB , Anderson JL , Hammond EH , Zhao L , Trehan S , Schwobe EP , et al.   Infection with Chlamydia pneumoniae accelerates the development of atherosclerosis and treatment with azithromycin prevents it in a rabbit model . Circulation . 1998;97:633–636
  37. Fong IW . Antibiotics effects in a rabbit model of Chlamydia pneumoniae-induced atherosclerosis . J Infect Dis . 2000;181(Suppl 3):S514–S518
  38. Gupta S , Leatham EW , Carrington D , Mendall MA , Kaski JC , Camm AJ . Elevated Chlamydia pneumoniae antibodies, cardiovascular events, and azithromycin in male survivors of myocardial infarction . Circulation . 1997;96:404–407
  39. Gurfinkel E , Bozovich G , Daroca A , Beck E , Manther B  ROXIS Study Group . Randomised trial of roxithromycin in non-Q-wave coronary syndromes (ROXIS Pilot Study) . Lancet . 1997;350:404–407
  40. Gurfinkel E , Bozovich G , Beck E , Testa E , Livellara B , Manther B . Treatment with the antibiotic roxithromycin in patients with acute non-Q-wave coronary syndromes. The final report of the ROXIS Study . Eur Heart J . 1999;20:121–127
  41. Muhlestein JB , Anderson JL , Carlquist JF , et al.   Randomized secondary prevention trial of azithromycin in patients with coronary artery disease (primary clinical results of the ACADEMIC study) . Circulation . 2000;102:1755–1760
  42. Anderson JL , Muhlestein JB . The ACADEMIC study in perspective (Azithromycin in coronary artery disease (elimination of myocardial infection with Chlamydia)) . J Infect Dis . 2000;181(Suppl 3):S569–S571
  43. O’Connor CM , Dunne MW , Pfeffer MA , et al.   Azithromycin for the secondary prevention of coronary heart disease events: the WIZARD study: a randomized controlled trial . JAMA . 2003;290:1459–1466
  44. Grayston JT , Kronmal RA , Jackson LA , Muhlestein JB , Yao L , Gupta S , et al.   Azithromycin for the secondary prevention of coronary events . N Engl J Med . 2005;352:1637–1645
  45. Cannon CP , Braunwald E , McCabe CH , Grayston JT , Muhlestein JB , Giugliano RP , et al.   Antibiotic treatment of Chlamydia pneumoniae after acute coronary syndrome . N Engl J Med . 2005;352:1646–1654
  46. Moazed TC , Kuo CC , Grayston JT , Campbell LA . Evidence of systemic dissemination of Chlamydia pneumoniae via macrophages in the mouse . J Infect Dis . 1998;177:1322–1325
  47. Gieffers J , van Zandbergen G , Rupp J , Sayk F , Kruger S , Ehlers S , et al.   Phagocytes transmit Chlamydia pneumoniae from the lungs to the vasculature . Eur Respir J . 2004;23:506–510
  48. Gaydos CA . Growth in vascular cells and cytokine production by Chlamydia pneumoniae . J Infect Dis . 2000;181(Suppl 3):S473–S478
  49. Kaukoranta-Tolvanen SS , Teppo AM , Laitinen K , Saikku P , Linnavuori K , Leinonen M . Growth of Chlamydia pneumoniae in cultured human peripheral blood mononuclear cells and induction of a cytokine response . Microb Pathog . 1996;21:215–221
  50. Fryer RH , Schwobe EP , Woods ML , Rodgers GM . Chlamydia species infect human vascular endothelial cells and induce procoagulant activity . J Investig Med . 1997;45:168–174
  51. Moazed TC , Kuo C , Grayston JT , Campbell LA . Murine models of Chlamydia pneumoniae infection and atherosclerosis . J Infect Dis . 1997;175:883–890
  52. Dechend R , Maass M , Gieffers J , Deitz R , Scheidereit C , Leutz A , et al.   Chlamydia pneumoniae infection of vascular smooth muscle and endothelial cells activates NF-kappaB and induces tissue factor and PAI-1 expression (a potential link to accelerated arteriosclerosis) . Circulation . 1999;100:1369–1373
  53. Maass M , Jahn J , Gieffers J , Danhoff C , Katus HA , Solbach W . Detection of Chlamydia pneumoniae within peripheral blood monocytes of patients with unstable angina or myocardial infarction . J Infect Dis . 2000;181(Suppl 3):S449–S451
  54. Liuba P , Karnani P , Pesonen E , Pakkari I , Forslid A , Johansson L , et al.   Endothelial dysfunction after repeated Chlamydia pneumoniae infection in apolipoprotein E-knockout mice . Circulation . 2000;102:1039–1044
  55. Molestina RE , Miller RD , Ramirez JA , Summersgill JT . Infection of human endothelial cells with Chlamydia pneumoniae stimulates transendothelial migration of neutrophils and monocytes . Infect Immun . 1999;67:1323–1330
  56. Coombes BK , Mahony JB . Chlamydia pneumoniae infection of human endothelial cells induces proliferation of smooth muscle cells via an endothelial cell-derived soluble factor(s) . Infect Immun . 1999;67:2909–2915
  57. Miller SA , Selzman CH , Shames BD , Barton HA , Johnston SM , Harken AH . Chlamydia pneumoniae activates nuclear factor kappaB and activator protein 1 in human vascular smooth muscle and induces cellular proliferation . J Surg Res . 2000;90:76–81
  58. Summersgill JT , Sahney NN , Gaydos CA , Quinn TC , Ramirez JA . Inhibition of Chlamydia pneumoniae growth in HEp-2 cells pretreated with gamma interferon and tumor necrosis factor alpha . Infect Immun . 1995;63:2801–2803
  59. Netea MG , Selzman CH , Kullberg BJ , Aalama JM , Weinberg A , Stalenhoef AF , et al.   Acellular components of Chlamydia pneumoniae stimulate cytokine production in human blood mononuclear cells . Eur J Immunol . 2000;30:541–549
  60. Geng Y , Shane RB , Berencsi K , Gonczol E , Zaki MH , Margolis DJ , et al.   Chlamydia pneumoniae inhibits apoptosis in human peripheral blood mononuclear cells through induction of IL-10 . J Immunol . 2000;164:5522–5529
  61. Kothe H , Dalhoff K , Rupp J , Muller A , Krenzer J , Maass M , et al.   Hydroxymethylglutaryl coenzyme A reductase inhibitors modify the inflammatory response of human macrophages and endothelial cells infected with Chlamydia pneumoniae . Circulation . 2000;101:1760–1763
  62. Stemme S , Hansson GK . Immune mechanisms in atherogenesis . Ann Med . 1994;26:141–146
  63. Halme S , Juvonen T , Laurila A , Juvonen J , Mosorin M , Saikku P , et al.   Chlamydia pneumoniae reactive T lymphocytes in the walls of abdominal aortic aneurysms . Eur J Clin Invest . 1999;29:546–552
  64. de Boer OJ , van der Wal AC , Houtkamp MA , Ossewaarde JM , Teeling P , Becher AE . Unstable atherosclerotic plaques contain T-cells that respond to Chlamydia pneumoniae . Cardiovasc Res . 2000;48:402–408
  65. Mosorin M , Surcel HM , Laurila A , Lehtinen M , Karttunen R , Juvonen J , et al.   Detection of Chlamydia pneumoniae-reactive T lymphocytes in human atherosclerotic plaques of carotid artery . Arterioscler Thromb Vasc Biol . 2000;20:1061–1067
  66. Kol A , Sukhova GK , Lichtman AH , Libby P . Chlamydial heat shock protein 60 localizes in human atheroma and regulates macrophage tumor necrosis factor-alpha and matrix metalloproteinase expression . Circulation . 1998;98:300–307
  67. Vehmaan-Kreula P , Puolakkainen M , Sarvas M , Welgus GH , Kovanen PT . Chlamydia pneumoniae proteins induce secretion of the 92-kDa gelatinase by human monocyte- derived macrophages . Arterioscler Thromb Vasc Biol . 2001;21:E1–E8
  68. Kalayoglu MV , Byrne GI . Induction of macrophage foam cell formation by Chlamydia pneumoniae . J Infect Dis . 1998;177:725–729
  69. Kalayoglu MV , Byrne GI . A Chlamydia pneumoniae component that induces macrophage foam cell formation is chlamydial lipopolysaccharide . Infect Immun . 1998;66:5067–5072
  70. Kalayoglu MV , Miranpuri GS , Golenbock DT , Byrne GI . Characterization of low-density lipoprotein uptake by murine macrophages exposed to Chlamydia pneumoniae . Microbes Infect . 1999;1:409–418
  71. Kalayoglu MV , Hoerneman B , LaVerda D , Morrison SG , Morrison RP , Byrne GI . Cellular oxidation of low-density lipoprotein by Chlamydia pneumoniae . J Infect Dis . 1999;180:780–790
  72. Xu Q , Hu Y , Kleindienst R , Wick G . Nitric oxide induces heat-shock protein 70 expression in vascular smooth muscle cells via activation of heat shock factor 1 . J Clin Invest . 1997;100:1089–1097
  73. Lis J , Wu C . Protein traffic on the heat shock promoter (parking, stalling, and trucking along) . Cell . 1993;74:1–4
  74. Schett G , Metzler B , Mayr M , Amberger A , Neiderwieser D , Gupta RS , et al.   Macrophage-lysis mediated by autoantibodies to heat shock protein 65/60 . Atherosclerosis . 1997;128:27–38
  75. Lamb DJ , Tickner ML , Dreux AC , El-Sankary W , Hourani SM , Eales-Reynolds LJ , et al.   Impairment of vascular function following BCG immunisation is associated with immune responses to HSP-60 in the cholesterol-fed rabbit . Atherosclerosis . 2004;172:13–20
  76. Hu H , Pierce GN , Zhong G . The atherogenic effects of Chlamydia are dependent on serum cholesterol and specific to Chlamydia pneumoniae . J Clin Invest . 1999;103:747–753
  77. Campbell LA , Blessing E , Rosenfeld M , Lin T , Kuo C . Mouse models of C pneumoniae infection and atherosclerosis . J Infect Dis . 2000;181(Suppl 3):S508–S513
  78. Blessing E , Lin TM , Campbell LA , Rosenfeld ME , Lloyd D , Kuo C . Chlamydia pneumoniae induces inflammatory changes in the heart and aorta of normocholesterolemic C57BL/6J mice . Infect Immun . 2000;68:4765–4768
  79. Fong IW , Chiu B , Viira E , Fong MW , Jang D , Mahony J . Rabbit model for Chlamydia pneumoniae infection . J Clin Microbiol . 1997;35:48–52
  80. Laitinen K , Laurila A , Pyhala L , Leinonen M , Saikku P . Chlamydia pneumoniae infection induces inflammatory changes in the aortas of rabbits . Infect Immun . 1997;65:4832–4835
  81. Muhlestein JB . Chlamydia pneumoniae-induced atherosclerosis in a rabbit model . J Infect Dis . 2000;181(Suppl 3):S505–S507
  82. Coombes BK , Chiu B , Fong IW , Mahony JB . Chlamydia pneumoniae infection of endothelial cells induces transcriptional activation of platelet-derived growth factor-B (a potential link to intimal thickening in a rabbit model of atherosclerosis) . J Infect Dis . 2002;185:1621–1630
  83. Liuba P , Pesonen E , Paakkari I , Batra S , Forslid A , Kovanen P , et al.   Acute Chlamydia pneumoniae infection causes coronary endothelial dysfunction in pigs . Atherosclerosis . 2003;167:215–222
  84. Chesebro BB , Blessing E , Kuo CC , Rosenfeld ME , Puolakkainen M , Campbell LA . Nitric oxide synthase plays a role in Chlamydia pneumoniae-induced atherosclerosis . Cardiovasc Res . 2003;60:170–174
  85. Campbell LA , O’Brien ER , Cappuccio AL , Kuo CC , Wang SP , Steward D , et al.   Detection of Chlamydia pneumoniae TWAR in human coronary atherectomy tissues . J Infect Dis . 1995;172:585–588

 This work was supported by National Institutes of Health Grants R01 HL65916, R01 HL72716, R01 EB-002436 and R01 HL083471 (C. C.); R01 DE15543 and R21 AT003094 (Q. Y.); R01 HL75824 (A. B. L.).

 Competition of interest: none.

PII: S0741-5214(06)00413-7

doi: 10.1016/j.jvs.2006.02.050

Journal of Vascular Surgery
Volume 43, Issue 6 , Pages 1301-1307 , June 2006

Article Tools