Skip to main content
PMC home page
Journal of Clinical Pathology logoLink to Journal of Clinical Pathology
. 1998 Nov;51(11):812–817. doi: 10.1136/jcp.51.11.812

Chlamydia pneumoniae in atheroma: consideration of criteria for causality.

A Shor 1, J I Phillips 1, G Ong 1, B J Thomas 1, D Taylor-Robinson 1
PMCID: PMC500974  PMID: 10193321

Abstract

AIMS: (1) To seek evidence of the existence of Chlamydia pneumoniae in a spectrum of atheromatous lesions in different types of arteries from individuals of different ages, using a polymerase chain reaction (PCR) assay supported by electron microscopy and immunocytochemistry; (2) to use electron microscopy to examine interactions between C pneumoniae and the cells present in the arterial tissue; (3) to assess the extent to which the data fulfil the criteria for causality. METHODS: At necropsy examination, 35 arterial specimens were taken from 25 subjects. The grade of atheroma was determined macroscopically and microscopically and the tissues coded and examined by the three techniques. RESULTS: Of the 35 specimens, 24 had macroscopic or microscopic atheromatous lesions of varying degree. Twenty two of the 35 specimens were examined by electron microscopy, C pneumoniae-like bodies being found in 11 (50%); seven specimens were examined by the immunocytochemical method, positive staining being detected in three; and all specimens were examined by the PCR technique, 15 (43%) being PCR positive. Overall, of the 24 specimens with lesions, 17 (71%) were positive by at least one of the three tests, whereas of the 11 specimens without lesions, only one was positive. The positive specimens comprised 10 of 19 aortas, three of six iliac arteries, and one coronary and one pulmonary artery. C pneumoniae was detected in four of six specimens in which there were early changes and in a 20 year old subject. Concerning the 25 subjects, of 17 who had atheromatous arteries, 14 (82%) were C pneumoniae positive and of the eight who had normal arteries, none was positive. CONCLUSIONS: There is a strong correlation between C pneumoniae and arterial atheromatous lesions. The organism may contribute to the disease process by damaging smooth muscle cells.

Full text

PDF

Images in this article

814Image
on p.814
814Image
on p.814

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Blanchard T., Bailey R., Holland M., Mabey D. Chlamydia pneumoniae and atherosclerosis. Lancet. 1993 Mar 27;341(8848):825–825. doi: 10.1016/0140-6736(93)90597-a. [DOI] [PubMed] [Google Scholar]
  2. Campbell L. A., O'Brien E. R., Cappuccio A. L., Kuo C. C., Wang S. P., Stewart D., Patton D. L., Cummings P. K., Grayston J. T. Detection of Chlamydia pneumoniae TWAR in human coronary atherectomy tissues. J Infect Dis. 1995 Aug;172(2):585–588. doi: 10.1093/infdis/172.2.585. [DOI] [PubMed] [Google Scholar]
  3. Gaydos C. A., Summersgill J. T., Sahney N. N., Ramirez J. A., Quinn T. C. Replication of Chlamydia pneumoniae in vitro in human macrophages, endothelial cells, and aortic artery smooth muscle cells. Infect Immun. 1996 May;64(5):1614–1620. doi: 10.1128/iai.64.5.1614-1620.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Grayston J. T. Infections caused by Chlamydia pneumoniae strain TWAR. Clin Infect Dis. 1992 Nov;15(5):757–761. doi: 10.1093/clind/15.5.757. [DOI] [PubMed] [Google Scholar]
  5. Grayston J. T., Kuo C. C., Coulson A. S., Campbell L. A., Lawrence R. D., Lee M. J., Strandness E. D., Wang S. P. Chlamydia pneumoniae (TWAR) in atherosclerosis of the carotid artery. Circulation. 1995 Dec 15;92(12):3397–3400. doi: 10.1161/01.cir.92.12.3397. [DOI] [PubMed] [Google Scholar]
  6. Grayston J. T., Kuo C. C., Wang S. P., Altman J. A new Chlamydia psittaci strain, TWAR, isolated in acute respiratory tract infections. N Engl J Med. 1986 Jul 17;315(3):161–168. doi: 10.1056/NEJM198607173150305. [DOI] [PubMed] [Google Scholar]
  7. Gupta S., Leatham E. W., Carrington D., Mendall M. A., Kaski J. C., Camm A. J. Elevated Chlamydia pneumoniae antibodies, cardiovascular events, and azithromycin in male survivors of myocardial infarction. Circulation. 1997 Jul 15;96(2):404–407. doi: 10.1161/01.cir.96.2.404. [DOI] [PubMed] [Google Scholar]
  8. Gurfinkel E., Bozovich G., Daroca A., Beck E., Mautner B. Randomised trial of roxithromycin in non-Q-wave coronary syndromes: ROXIS Pilot Study. ROXIS Study Group. Lancet. 1997 Aug 9;350(9075):404–407. doi: 10.1016/s0140-6736(97)07201-2. [DOI] [PubMed] [Google Scholar]
  9. HILL A. B. THE ENVIRONMENT AND DISEASE: ASSOCIATION OR CAUSATION? Proc R Soc Med. 1965 May;58:295–300. [PMC free article] [PubMed] [Google Scholar]
  10. Jackson L. A., Campbell L. A., Kuo C. C., Grayston J. T. Detection of Chlamydia pneumoniae in atheroma specimens. J Infect Dis. 1996 Oct;174(4):893–896. doi: 10.1093/infdis/174.4.893. [DOI] [PubMed] [Google Scholar]
  11. Jackson L. A., Campbell L. A., Kuo C. C., Rodriguez D. I., Lee A., Grayston J. T. Isolation of Chlamydia pneumoniae from a carotid endarterectomy specimen. J Infect Dis. 1997 Jul;176(1):292–295. doi: 10.1086/517270. [DOI] [PubMed] [Google Scholar]
  12. Jackson L. A., Campbell L. A., Schmidt R. A., Kuo C. C., Cappuccio A. L., Lee M. J., Grayston J. T. Specificity of detection of Chlamydia pneumoniae in cardiovascular atheroma: evaluation of the innocent bystander hypothesis. Am J Pathol. 1997 May;150(5):1785–1790. [PMC free article] [PubMed] [Google Scholar]
  13. Knoebel E., Vijayagopal P., Figueroa J. E., 2nd, Martin D. H. In vitro infection of smooth muscle cells by Chlamydia pneumoniae. Infect Immun. 1997 Feb;65(2):503–506. doi: 10.1128/iai.65.2.503-506.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kuo C. C., Coulson A. S., Campbell L. A., Cappuccio A. L., Lawrence R. D., Wang S. P., Grayston J. T. 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 Jul;26(1):29–31. doi: 10.1016/s0741-5214(97)70143-5. [DOI] [PubMed] [Google Scholar]
  15. Kuo C. C., Gown A. M., Benditt E. P., Grayston J. T. Detection of Chlamydia pneumoniae in aortic lesions of atherosclerosis by immunocytochemical stain. Arterioscler Thromb. 1993 Oct;13(10):1501–1504. doi: 10.1161/01.atv.13.10.1501. [DOI] [PubMed] [Google Scholar]
  16. Kuo C. C., Shor A., Campbell L. A., Fukushi H., Patton D. L., Grayston J. T. Demonstration of Chlamydia pneumoniae in atherosclerotic lesions of coronary arteries. J Infect Dis. 1993 Apr;167(4):841–849. doi: 10.1093/infdis/167.4.841. [DOI] [PubMed] [Google Scholar]
  17. Leinonen M., Linnanmäki E., Mattila K., Nieminen M. S., Valtonen V., Leirisalo-Repo M., Saikku P. Circulating immune complexes containing chlamydial lipopolysaccharide in acute myocardial infarction. Microb Pathog. 1990 Jul;9(1):67–73. doi: 10.1016/0882-4010(90)90042-o. [DOI] [PubMed] [Google Scholar]
  18. Linnanmäki E., Leinonen M., Mattila K., Nieminen M. S., Valtonen V., Saikku P. Chlamydia pneumoniae-specific circulating immune complexes in patients with chronic coronary heart disease. Circulation. 1993 Apr;87(4):1130–1134. doi: 10.1161/01.cir.87.4.1130. [DOI] [PubMed] [Google Scholar]
  19. Maseri A., Biasucci L. M., Liuzzo G. Inflammation in ischaemic heart disease. BMJ. 1996 Apr 27;312(7038):1049–1050. doi: 10.1136/bmj.312.7038.1049. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Melnick S. L., Shahar E., Folsom A. R., Grayston J. T., Sorlie P. D., Wang S. P., Szklo M. Past infection by Chlamydia pneumoniae strain TWAR and asymptomatic carotid atherosclerosis. Atherosclerosis Risk in Communities (ARIC) Study Investigators. Am J Med. 1993 Nov;95(5):499–504. doi: 10.1016/0002-9343(93)90332-j. [DOI] [PubMed] [Google Scholar]
  21. Mendall M. A., Patel P., Ballam L., Strachan D., Northfield T. C. C reactive protein and its relation to cardiovascular risk factors: a population based cross sectional study. BMJ. 1996 Apr 27;312(7038):1061–1065. doi: 10.1136/bmj.312.7038.1061. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Moazed T. C., Kuo C., Grayston J. T., Campbell L. A. Murine models of Chlamydia pneumoniae infection and atherosclerosis. J Infect Dis. 1997 Apr;175(4):883–890. doi: 10.1086/513986. [DOI] [PubMed] [Google Scholar]
  23. Muhlestein J. B., Anderson J. L., Hammond E. H., Zhao L., Trehan S., Schwobe E. P., Carlquist J. F. Infection with Chlamydia pneumoniae accelerates the development of atherosclerosis and treatment with azithromycin prevents it in a rabbit model. Circulation. 1998 Feb 24;97(7):633–636. doi: 10.1161/01.cir.97.7.633. [DOI] [PubMed] [Google Scholar]
  24. Nadji M. Immunoperoxidase techniques. I. Facts and artifacts. Am J Dermatopathol. 1986 Feb;8(1):32–36. doi: 10.1097/00000372-198602000-00006. [DOI] [PubMed] [Google Scholar]
  25. Ong G., Thomas B. J., Mansfield A. O., Davidson B. R., Taylor-Robinson D. Detection and widespread distribution of Chlamydia pneumoniae in the vascular system and its possible implications. J Clin Pathol. 1996 Feb;49(2):102–106. doi: 10.1136/jcp.49.2.102. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Patel P., Mendall M. A., Carrington D., Strachan D. P., Leatham E., Molineaux N., Levy J., Blakeston C., Seymour C. A., Camm A. J. Association of Helicobacter pylori and Chlamydia pneumoniae infections with coronary heart disease and cardiovascular risk factors. BMJ. 1995 Sep 16;311(7007):711–714. doi: 10.1136/bmj.311.7007.711. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Phillips J. I., Isaacson C., Carman H. Ochronosis in black South Africans who used skin lighteners. Am J Dermatopathol. 1986 Feb;8(1):14–21. doi: 10.1097/00000372-198602000-00003. [DOI] [PubMed] [Google Scholar]
  28. Phillips J. I. Lack of cilia and squamous metaplasia in upper respiratory tract biopsies from children. S Afr Med J. 1989 Oct 7;76(7):355–357. [PubMed] [Google Scholar]
  29. Ramirez J. A. Isolation of Chlamydia pneumoniae from the coronary artery of a patient with coronary atherosclerosis. The Chlamydia pneumoniae/Atherosclerosis Study Group. Ann Intern Med. 1996 Dec 15;125(12):979–982. doi: 10.7326/0003-4819-125-12-199612150-00008. [DOI] [PubMed] [Google Scholar]
  30. Ridker P. M., Cushman M., Stampfer M. J., Tracy R. P., Hennekens C. H. Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med. 1997 Apr 3;336(14):973–979. doi: 10.1056/NEJM199704033361401. [DOI] [PubMed] [Google Scholar]
  31. Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature. 1993 Apr 29;362(6423):801–809. doi: 10.1038/362801a0. [DOI] [PubMed] [Google Scholar]
  32. Saikku P., Leinonen M., Mattila K., Ekman M. R., Nieminen M. S., Mäkelä P. H., Huttunen J. K., Valtonen V. Serological evidence of an association of a novel Chlamydia, TWAR, with chronic coronary heart disease and acute myocardial infarction. Lancet. 1988 Oct 29;2(8618):983–986. doi: 10.1016/s0140-6736(88)90741-6. [DOI] [PubMed] [Google Scholar]
  33. Saikku P., Leinonen M., Tenkanen L., Linnanmäki E., Ekman M. R., Manninen V., Mänttäri M., Frick M. H., Huttunen J. K. Chronic Chlamydia pneumoniae infection as a risk factor for coronary heart disease in the Helsinki Heart Study. Ann Intern Med. 1992 Feb 15;116(4):273–278. doi: 10.7326/0003-4819-116-4-273. [DOI] [PubMed] [Google Scholar]
  34. Shor A., Kuo C. C., Patton D. L. Detection of Chlamydia pneumoniae in coronary arterial fatty streaks and atheromatous plaques. S Afr Med J. 1992 Sep;82(3):158–161. [PubMed] [Google Scholar]
  35. Thom D. H., Grayston J. T., Siscovick D. S., Wang S. P., Weiss N. S., Daling J. R. Association of prior infection with Chlamydia pneumoniae and angiographically demonstrated coronary artery disease. JAMA. 1992 Jul 1;268(1):68–72. [PubMed] [Google Scholar]
  36. Thom D. H., Wang S. P., Grayston J. T., Siscovick D. S., Stewart D. K., Kronmal R. A., Weiss N. S. Chlamydia pneumoniae strain TWAR antibody and angiographically demonstrated coronary artery disease. Arterioscler Thromb. 1991 May-Jun;11(3):547–551. doi: 10.1161/01.atv.11.3.547. [DOI] [PubMed] [Google Scholar]
  37. Weiss S. M., Roblin P. M., Gaydos C. A., Cummings P., Patton D. L., Schulhoff N., Shani J., Frankel R., Penney K., Quinn T. C. Failure to detect Chlamydia pneumoniae in coronary atheromas of patients undergoing atherectomy. J Infect Dis. 1996 Apr;173(4):957–962. doi: 10.1093/infdis/173.4.957. [DOI] [PubMed] [Google Scholar]
  38. Wissler R. W. Significance of Chlamydia pneumoniae (TWAR) in atherosclerotic lesions. Circulation. 1995 Dec 15;92(12):3376–3376. doi: 10.1161/01.cir.92.12.3376. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Pathology are provided here courtesy of BMJ Publishing Group

RESOURCES