Skip to main content
NCBI home page
Journal of Clinical Pathology logoLink to Journal of Clinical Pathology
. 2000 Sep;53(9):647–654. doi: 10.1136/jcp.53.9.647

Microorganisms in the aetiology of atherosclerosis

S Morre 1, W Stooker 1, W Lagrand 1, A J C van den Brule 1, H Niessen 1
PMCID: PMC1731245  PMID: 11041053

Abstract

Recent publications have suggested that infective pathogens might play an important role in the pathogenesis of atherosclerosis. This review focuses on these microorganisms in the process of atherosclerosis. The results of in vitro studies, animal studies, tissue studies, and serological studies will be summarised, followed by an overall conclusion concerning the strength of the association of the microorganism with the pathogenesis of atherosclerosis. The role of the bacteria Chlamydia pneumoniae and Helicobacter pylori, and the viruses human immunodeficiency virus, coxsackie B virus, cytomegalovirus, Epstein-Barr virus, herpes simplex virus, and measles virus will be discussed.

Key Words: atherosclerosis • Chlamydia pneumoniae • Helicobacter pylori

Full Text

The Full Text of this article is available as a PDF (221.6 KB).

Selected References

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

  1. Adam E., Melnick J. L., DeBakey M. E. Cytomegalovirus infection and atherosclerosis. Cent Eur J Public Health. 1997 Sep;5(3):99–106. [PubMed] [Google Scholar]
  2. Adam E., Melnick J. L., Probtsfield J. L., Petrie B. L., Burek J., Bailey K. R., McCollum C. H., DeBakey M. E. High levels of cytomegalovirus antibody in patients requiring vascular surgery for atherosclerosis. Lancet. 1987 Aug 8;2(8554):291–293. doi: 10.1016/s0140-6736(87)90888-9. [DOI] [PubMed] [Google Scholar]
  3. Adams M. R., Nakagomi A., Keech A., Robinson J., McCredie R., Bailey B. P., Freedman S. B., Celermajer D. S. Carotid intima-media thickness is only weakly correlated with the extent and severity of coronary artery disease. Circulation. 1995 Oct 15;92(8):2127–2134. doi: 10.1161/01.cir.92.8.2127. [DOI] [PubMed] [Google Scholar]
  4. Adler S. P., Hur J. K., Wang J. B., Vetrovec G. W. Prior infection with cytomegalovirus is not a major risk factor for angiographically demonstrated coronary artery atherosclerosis. J Infect Dis. 1998 Jan;177(1):209–212. doi: 10.1086/517355. [DOI] [PubMed] [Google Scholar]
  5. Altman R., Rouvier J., Scazziota A., Absi R. S., Gonzalez C. Lack of association between prior infection with Chlamydia pneumoniae and acute or chronic coronary artery disease. Clin Cardiol. 1999 Feb;22(2):85–90. doi: 10.1002/clc.4960220206. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Anderson J. L., Muhlestein J. B., Carlquist J., Allen A., Trehan S., Nielson C., Hall S., Brady J., Egger M., Horne B. Randomized secondary prevention trial of azithromycin in patients with coronary artery disease and serological evidence for Chlamydia pneumoniae infection: The Azithromycin in Coronary Artery Disease: Elimination of Myocardial Infection with Chlamydia (ACADEMIC) study. Circulation. 1999 Mar 30;99(12):1540–1547. doi: 10.1161/01.cir.99.12.1540. [DOI] [PubMed] [Google Scholar]
  7. Andreasen J. J., Farholt S., Jensen J. S. Failure to detect Chlamydia pneumoniae in calcific and degenerative arteriosclerotic aortic valves excised during open heart surgery. APMIS. 1998 Jul;106(7):717–720. [PubMed] [Google Scholar]
  8. Bachmaier K., Neu N., de la Maza L. M., Pal S., Hessel A., Penninger J. M. Chlamydia infections and heart disease linked through antigenic mimicry. Science. 1999 Feb 26;283(5406):1335–1339. doi: 10.1126/science.283.5406.1335. [DOI] [PubMed] [Google Scholar]
  9. Bartels C., Maass M., Bein G., Malisius R., Brill N., Bechtel J. F., Sayk F., Feller A. C., Sievers H. H. Detection of Chlamydia pneumoniae but not cytomegalovirus in occluded saphenous vein coronary artery bypass grafts. Circulation. 1999 Feb 23;99(7):879–882. doi: 10.1161/01.cir.99.7.879. [DOI] [PubMed] [Google Scholar]
  10. Bayad J., Galteau M. M., Siest G. Théorie virale de l'athérosclérose. Place du cytomégalovirus. Ann Biol Clin (Paris) 1993;51(2):101–107. [PubMed] [Google Scholar]
  11. Beck J. D., Slade G. D. Epidemiology of periodontal diseases. Curr Opin Periodontol. 1996;3:3–9. [PubMed] [Google Scholar]
  12. Berencsi K., Endresz V., Klurfeld D., Kari L., Kritchevsky D., Gönczöl E. Early atherosclerotic plaques in the aorta following cytomegalovirus infection of mice. Cell Adhes Commun. 1998 Jan;5(1):39–47. doi: 10.3109/15419069809005597. [DOI] [PubMed] [Google Scholar]
  13. Birnie D. H., Holme E. R., McKay I. C., Hood S., McColl K. E., Hillis W. S. 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 Mar;19(3):387–394. doi: 10.1053/euhj.1997.0618. [DOI] [PubMed] [Google Scholar]
  14. Blum A., Giladi M., Weinberg M., Kaplan G., Pasternack H., Laniado S., Miller H. High anti-cytomegalovirus (CMV) IgG antibody titer is associated with coronary artery disease and may predict post-coronary balloon angioplasty restenosis. Am J Cardiol. 1998 Apr 1;81(7):866–868. doi: 10.1016/s0002-9149(98)00019-8. [DOI] [PubMed] [Google Scholar]
  15. Boman J., Söderberg S., Forsberg J., Birgander L. S., Allard A., Persson K., Jidell E., Kumlin U., Juto P., Waldenström A. High prevalence of Chlamydia pneumoniae DNA in peripheral blood mononuclear cells in patients with cardiovascular disease and in middle-aged blood donors. J Infect Dis. 1998 Jul;178(1):274–277. doi: 10.1086/517452. [DOI] [PubMed] [Google Scholar]
  16. Capron L., Wyplosz B. Théorie infectieuse de l'athérosclérose. Arch Mal Coeur Vaiss. 1998 Oct;91(SPEC):21–26. [PubMed] [Google Scholar]
  17. Constans J., Marchand J. M., Conri C., Peuchant E., Seigneur M., Rispal P., Lasseur C., Pellegrin J. L., Leng B. Asymptomatic atherosclerosis in HIV-positive patients: A case-control ultrasound study. Ann Med. 1995 Dec;27(6):683–685. doi: 10.3109/07853899509019256. [DOI] [PubMed] [Google Scholar]
  18. Csonka E., Bayer P. I., Büki K., Várady G. Influence of the measles virus on the proliferation and protein synthesis of aortic endothelial and smooth muscle cells. Acta Microbiol Hung. 1990;37(2):193–200. [PubMed] [Google Scholar]
  19. Das U. N. Hypothesis: cis-unsaturated fatty acids as potential anti-peptic ulcer drugs. Prostaglandins Leukot Essent Fatty Acids. 1998 May;58(5):377–380. doi: 10.1016/s0952-3278(98)90074-6. [DOI] [PubMed] [Google Scholar]
  20. Davidson M., Kuo C. C., Middaugh J. P., Campbell L. A., Wang S. P., Newman W. P., 3rd, Finley J. C., Grayston J. T. Confirmed previous infection with Chlamydia pneumoniae (TWAR) and its presence in early coronary atherosclerosis. Circulation. 1998 Aug 18;98(7):628–633. doi: 10.1161/01.cir.98.7.628. [DOI] [PubMed] [Google Scholar]
  21. 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 Feb;30(2):299–305. doi: 10.1161/01.str.30.2.299. [DOI] [PubMed] [Google Scholar]
  22. Fang J. C., Kinlay S., Kundsin R., Ganz P. Chlamydia pneumoniae infection is frequent but not associated with coronary arteriosclerosis in cardiac transplant recipients. Am J Cardiol. 1998 Dec 15;82(12):1479–1483. doi: 10.1016/s0002-9149(98)00723-1. [DOI] [PubMed] [Google Scholar]
  23. Folsom A. R., Nieto F. J., Sorlie P., Chambless L. E., Graham D. Y. Helicobacter pylori seropositivity and coronary heart disease incidence. Atherosclerosis Risk In Communities (ARIC) Study Investigators. Circulation. 1998 Sep 1;98(9):845–850. doi: 10.1161/01.cir.98.9.845. [DOI] [PubMed] [Google Scholar]
  24. Gibbs R. G., Carey N., Davies A. H. Chlamydia pneumoniae and vascular disease. Br J Surg. 1998 Sep;85(9):1191–1197. doi: 10.1046/j.1365-2168.1998.00861.x. [DOI] [PubMed] [Google Scholar]
  25. Godzik K. L., O'Brien E. R., Wang S. K., Kuo C. C. In vitro susceptibility of human vascular wall cells to infection with Chlamydia pneumoniae. J Clin Microbiol. 1995 Sep;33(9):2411–2414. doi: 10.1128/jcm.33.9.2411-2414.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Grattan M. T., Moreno-Cabral C. E., Starnes V. A., Oyer P. E., Stinson E. B., Shumway N. E. Cytomegalovirus infection is associated with cardiac allograft rejection and atherosclerosis. JAMA. 1989 Jun 23;261(24):3561–3566. [PubMed] [Google Scholar]
  27. 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]
  28. Griffiths P. D., Hannington G., Booth J. C. Coxsackie B virus infections and myocardial infarction. Results from a prospective, epidemiologically controlled study. Lancet. 1980 Jun 28;1(8183):1387–1389. doi: 10.1016/s0140-6736(80)92655-0. [DOI] [PubMed] [Google Scholar]
  29. Guetta E., Guetta V., Shibutani T., Epstein S. E. Monocytes harboring cytomegalovirus: interactions with endothelial cells, smooth muscle cells, and oxidized low-density lipoprotein. Possible mechanisms for activating virus delivered by monocytes to sites of vascular injury. Circ Res. 1997 Jul;81(1):8–16. doi: 10.1161/01.res.81.1.8. [DOI] [PubMed] [Google Scholar]
  30. 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]
  31. Gurfinkel E., Bozovich G., Beck E., Testa E., Livellara B., Mautner 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 Jan;20(2):121–127. doi: 10.1053/euhj.1998.1283. [DOI] [PubMed] [Google Scholar]
  32. 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]
  33. Hajjar D. P., Pomerantz K. B., Falcone D. J., Weksler B. B., Grant A. J. Herpes simplex virus infection in human arterial cells. Implications in arteriosclerosis. J Clin Invest. 1987 Nov;80(5):1317–1321. doi: 10.1172/JCI113208. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Halme S., Syrjälä H., Bloigu A., Saikku P., Leinonen M., Airaksinen J., Surcel H. M. Lymphocyte responses to Chlamydia antigens in patients with coronary heart disease. Eur Heart J. 1997 Jul;18(7):1095–1101. doi: 10.1093/oxfordjournals.eurheartj.a015403. [DOI] [PubMed] [Google Scholar]
  35. Hendrix M. G., Dormans P. H., Kitslaar P., Bosman F., Bruggeman C. A. The presence of cytomegalovirus nucleic acids in arterial walls of atherosclerotic and nonatherosclerotic patients. Am J Pathol. 1989 May;134(5):1151–1157. [PMC free article] [PubMed] [Google Scholar]
  36. Hendrix M. G., Salimans M. M., van Boven C. P., Bruggeman C. A. High prevalence of latently present cytomegalovirus in arterial walls of patients suffering from grade III atherosclerosis. Am J Pathol. 1990 Jan;136(1):23–28. [PMC free article] [PubMed] [Google Scholar]
  37. Herzum M., Schaefer J. R., Hufnagel G., Maisch B. Zytomegalie- und Herpes-simplex-Viren in Pathogenese und Progression der nativen Arteriosklerose und der Rezidivstenose nach Intervention. Herz. 1998 May;23(3):193–196. doi: 10.1007/BF03044605. [DOI] [PubMed] [Google Scholar]
  38. Hu H., Pierce G. N., Zhong G. The atherogenic effects of chlamydia are dependent on serum cholesterol and specific to Chlamydia pneumoniae. J Clin Invest. 1999 Mar;103(5):747–753. doi: 10.1172/JCI4582. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Ilbäck N. G., Mohammed A., Fohlman J., Friman G. Cardiovascular lipid accumulation with Coxsackie B virus infection in mice. Am J Pathol. 1990 Jan;136(1):159–167. [PMC free article] [PubMed] [Google Scholar]
  40. 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]
  41. Jacob H. S., Visser M., Key N. S., Goodman J. L., Moldow C. F., Vercellotti G. M. Herpes virus infection of endothelium: new insights into atherosclerosis. Trans Am Clin Climatol Assoc. 1992;103:95–104. [PMC free article] [PubMed] [Google Scholar]
  42. Jander S., Sitzer M., Schumann R., Schroeter M., Siebler M., Steinmetz H., Stoll G. Inflammation in high-grade carotid stenosis: a possible role for macrophages and T cells in plaque destabilization. Stroke. 1998 Aug;29(8):1625–1630. doi: 10.1161/01.str.29.8.1625. [DOI] [PubMed] [Google Scholar]
  43. Juvonen J., Juvonen T., Laurila A., Alakärppä H., Lounatmaa K., Surcel H. M., Leinonen M., Kairaluoma M. I., Saikku P. Demonstration of Chlamydia pneumoniae in the walls of abdominal aortic aneurysms. J Vasc Surg. 1997 Mar;25(3):499–505. doi: 10.1016/s0741-5214(97)70260-x. [DOI] [PubMed] [Google Scholar]
  44. Kalayoglu M. V., Byrne G. I. A Chlamydia pneumoniae component that induces macrophage foam cell formation is chlamydial lipopolysaccharide. Infect Immun. 1998 Nov;66(11):5067–5072. doi: 10.1128/iai.66.11.5067-5072.1998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Kalayoglu M. V., Byrne G. I. Induction of macrophage foam cell formation by Chlamydia pneumoniae. J Infect Dis. 1998 Mar;177(3):725–729. doi: 10.1086/514241. [DOI] [PubMed] [Google Scholar]
  46. Kaner R. J., Medina J., Nicholson A. C., Ursea R., Schwartz S. M., Hajjar D. P. Developmentally regulated herpesvirus plaque formation in arterial smooth muscle cells. Circ Res. 1993 Jul;73(1):10–14. doi: 10.1161/01.res.73.1.10. [DOI] [PubMed] [Google Scholar]
  47. Key N. S., Bach R. R., Vercellotti G. M., Moldow C. F. Herpes simplex virus type I does not require productive infection to induce tissue factor in human umbilical vein endothelial cells. Lab Invest. 1993 Jun;68(6):645–651. [PubMed] [Google Scholar]
  48. Key N. S., Vercellotti G. M., Winkelmann J. C., Moldow C. F., Goodman J. L., Esmon N. L., Esmon C. T., Jacob H. S. Infection of vascular endothelial cells with herpes simplex virus enhances tissue factor activity and reduces thrombomodulin expression. Proc Natl Acad Sci U S A. 1990 Sep;87(18):7095–7099. doi: 10.1073/pnas.87.18.7095. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Kol A., Sukhova G. K., Lichtman A. H., Libby P. Chlamydial heat shock protein 60 localizes in human atheroma and regulates macrophage tumor necrosis factor-alpha and matrix metalloproteinase expression. Circulation. 1998 Jul 28;98(4):300–307. doi: 10.1161/01.cir.98.4.300. [DOI] [PubMed] [Google Scholar]
  50. 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]
  51. 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]
  52. Kuo C. C., Grayston J. T., Campbell L. A., Goo Y. A., Wissler R. W., Benditt E. P. Chlamydia pneumoniae (TWAR) in coronary arteries of young adults (15-34 years old). Proc Natl Acad Sci U S A. 1995 Jul 18;92(15):6911–6914. doi: 10.1073/pnas.92.15.6911. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Kuo C., Campbell L. A. Is infection with Chlamydia pneumoniae a causative agent in atherosclerosis? Mol Med Today. 1998 Oct;4(10):426–430. doi: 10.1016/s1357-4310(98)01351-3. [DOI] [PubMed] [Google Scholar]
  54. Laitinen K., Laurila A., Pyhälä L., Leinonen M., Saikku P. Chlamydia pneumoniae infection induces inflammatory changes in the aortas of rabbits. Infect Immun. 1997 Nov;65(11):4832–4835. doi: 10.1128/iai.65.11.4832-4835.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Laurila A., Bloigu A., Näyhä S., Hassi J., Leinonen M., Saikku P. Association of Helicobacter pylori infection with elevated serum lipids. Atherosclerosis. 1999 Jan;142(1):207–210. doi: 10.1016/s0021-9150(98)00194-4. [DOI] [PubMed] [Google Scholar]
  56. Laurila A., Bloigu A., Näyhä S., Hassi J., Leinonen M., Saikku P. Chronic Chlamydia pneumoniae infection is associated with a serum lipid profile known to be a risk factor for atherosclerosis. Arterioscler Thromb Vasc Biol. 1997 Nov;17(11):2910–2913. doi: 10.1161/01.atv.17.11.2910. [DOI] [PubMed] [Google Scholar]
  57. Libby P., Aikawa M. New insights into plaque stabilisation by lipid lowering. Drugs. 1998;56 (Suppl 1):9–33. doi: 10.2165/00003495-199856001-00002. [DOI] [PubMed] [Google Scholar]
  58. Lindholt J. S., Ostergård L., Henneberg E. W., Fasting H., Andersen P. Failure to demonstrate Chlamydia pneumoniae in symptomatic abdominal aortic aneurysms by a nested polymerase chain reaction (PCR). Eur J Vasc Endovasc Surg. 1998 Feb;15(2):161–164. doi: 10.1016/s1078-5884(98)80138-x. [DOI] [PubMed] [Google Scholar]
  59. Loebe M., Schüler S., Spiegelsberger S., Warnecke H., Fleck E., Hetzer R. Cytomegalievirus-Infektion und Koronarsklerose nach Herztransplantation. Dtsch Med Wochenschr. 1990 Aug 24;115(34):1266–1269. doi: 10.1055/s-2008-1065151. [DOI] [PubMed] [Google Scholar]
  60. Maass M., Bartels C., Engel P. M., Mamat U., Sievers H. H. Endovascular presence of viable Chlamydia pneumoniae is a common phenomenon in coronary artery disease. J Am Coll Cardiol. 1998 Mar 15;31(4):827–832. doi: 10.1016/s0735-1097(98)00016-3. [DOI] [PubMed] [Google Scholar]
  61. Maass M., Krause E., Engel P. M., Krüger S. Endovascular presence of Chlamydia pneumoniae in patients with hemodynamically effective carotid artery stenosis. Angiology. 1997 Aug;48(8):699–706. doi: 10.1177/000331979704800805. [DOI] [PubMed] [Google Scholar]
  62. Markus H. S., Mendall M. A. Helicobacter pylori infection: a risk factor for ischaemic cerebrovascular disease and carotid atheroma. J Neurol Neurosurg Psychiatry. 1998 Jan;64(1):104–107. doi: 10.1136/jnnp.64.1.104. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Mattila K. J. Dental infections as a risk factor for acute myocardial infarction. Eur Heart J. 1993 Dec;14 (Suppl K):51–53. [PubMed] [Google Scholar]
  64. Mattila K. J., Valle M. S., Nieminen M. S., Valtonen V. V., Hietaniemi K. L. Dental infections and coronary atherosclerosis. Atherosclerosis. 1993 Nov;103(2):205–211. doi: 10.1016/0021-9150(93)90263-t. [DOI] [PubMed] [Google Scholar]
  65. Mattila K. J., Valtonen V. V., Nieminen M. S., Asikainen S. Role of infection as a risk factor for atherosclerosis, myocardial infarction, and stroke. Clin Infect Dis. 1998 Mar;26(3):719–734. doi: 10.1086/514570. [DOI] [PubMed] [Google Scholar]
  66. 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 Mar 30;99(12):1560–1566. doi: 10.1161/01.cir.99.12.1560. [DOI] [PubMed] [Google Scholar]
  67. Meier C. R., Derby L. E., Jick S. S., Vasilakis C., Jick H. Antibiotics and risk of subsequent first-time acute myocardial infarction. JAMA. 1999 Feb 3;281(5):427–431. doi: 10.1001/jama.281.5.427. [DOI] [PubMed] [Google Scholar]
  68. Melnick J. L., Adam E., Debakey M. E. Cytomegalovirus and atherosclerosis. Eur Heart J. 1993 Dec;14 (Suppl K):30–38. [PubMed] [Google Scholar]
  69. Melnick J. L., Petrie B. L., Dreesman G. R., Burek J., McCollum C. H., DeBakey M. E. Cytomegalovirus antigen within human arterial smooth muscle cells. Lancet. 1983 Sep 17;2(8351):644–647. doi: 10.1016/s0140-6736(83)92529-1. [DOI] [PubMed] [Google Scholar]
  70. 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]
  71. 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]
  72. 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]
  73. Molestina R. E., Dean D., Miller R. D., Ramirez J. A., Summersgill J. T. Characterization of a strain of Chlamydia pneumoniae isolated from a coronary atheroma by analysis of the omp1 gene and biological activity in human endothelial cells. Infect Immun. 1998 Apr;66(4):1370–1376. doi: 10.1128/iai.66.4.1370-1376.1998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  74. 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]
  75. Muhlestein J. B. Bacterial infections and atherosclerosis. J Investig Med. 1998 Oct;46(8):396–402. [PubMed] [Google Scholar]
  76. Muhlestein J. B., Hammond E. H., Carlquist J. F., Radicke E., Thomson M. J., Karagounis L. A., Woods M. L., Anderson J. L. 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 Jun;27(7):1555–1561. doi: 10.1016/0735-1097(96)00055-1. [DOI] [PubMed] [Google Scholar]
  77. Musiani M., Zerbini M. L., Muscari A., Puddu G. M., Gentilomi G., Gibellini D., Gallinella G., Puddu P., La Placa M. Antibody patterns against cytomegalovirus and Epstein-Barr virus in human atherosclerosis. Microbiologica. 1990 Jan;13(1):35–41. [PubMed] [Google Scholar]
  78. Musiani M., Zerbini M. L., Muscari A., Puddu G. M., Gentilomi G., Gibellini D., Gallinella G., Puddu P., La Placa M. Antibody patterns against cytomegalovirus and Epstein-Barr virus in human atherosclerosis. Microbiologica. 1990 Jan;13(1):35–41. [PubMed] [Google Scholar]
  79. Nicholls A. C., Thomas M. Coxsackie virus infection in acute myocardial infarction. Lancet. 1977 Apr 23;1(8017):883–884. doi: 10.1016/s0140-6736(77)91203-x. [DOI] [PubMed] [Google Scholar]
  80. Nicoletti A., Kaveri S., Caligiuri G., Bariéty J., Hansson G. K. Immunoglobulin treatment reduces atherosclerosis in apo E knockout mice. J Clin Invest. 1998 Sep 1;102(5):910–918. doi: 10.1172/JCI119892. [DOI] [PMC free article] [PubMed] [Google Scholar]
  81. Nieto F. J., Adam E., Sorlie P., Farzadegan H., Melnick J. L., Comstock G. W., Szklo M. Cohort study of cytomegalovirus infection as a risk factor for carotid intimal-medial thickening, a measure of subclinical atherosclerosis. Circulation. 1996 Sep 1;94(5):922–927. doi: 10.1161/01.cir.94.5.922. [DOI] [PubMed] [Google Scholar]
  82. Nyström-Rosander C., Thelin S., Hjelm E., Lindquist O., Påhlson C., Friman G. High incidence of Chlamydia pneumoniae in sclerotic heart valves of patients undergoing aortic valve replacement. Scand J Infect Dis. 1997;29(4):361–365. doi: 10.3109/00365549709011831. [DOI] [PubMed] [Google Scholar]
  83. Ossei-Gerning N., Moayyedi P., Smith S., Braunholtz D., Wilson J. I., Axon A. T., Grant P. J. Helicobacter pylori infection is related to atheroma in patients undergoing coronary angiography. Cardiovasc Res. 1997 Jul;35(1):120–124. doi: 10.1016/s0008-6363(97)00090-4. [DOI] [PubMed] [Google Scholar]
  84. Ossewaarde J. M., Feskens E. J., De Vries A., Vallinga C. E., Kromhout D. Chlamydia pneumoniae is a risk factor for coronary heart disease in symptom-free elderly men, but Helicobacter pylori and cytomegalovirus are not. Epidemiol Infect. 1998 Feb;120(1):93–99. doi: 10.1017/s0950268897008303. [DOI] [PMC free article] [PubMed] [Google Scholar]
  85. Paget C. J., Wolk S. W., Whitehouse W. M., Erlandson E. E., Lampman R. M., Schaldenbrand J., Fry W. J. Incidence and pathophysiologic significance of infected carotid artery plaque. Ann Vasc Surg. 1997 Mar;11(2):129–132. doi: 10.1007/s100169900022. [DOI] [PubMed] [Google Scholar]
  86. Paterson D. L., Hall J., Rasmussen S. J., Timms P. Failure to detect Chlamydia pneumoniae in atherosclerotic plaques of Australian patients. Pathology. 1998 May;30(2):169–172. doi: 10.1080/00313029800169166. [DOI] [PubMed] [Google Scholar]
  87. Paton P., Tabib A., Loire R., Tete R. Coronary artery lesions and human immunodeficiency virus infection. Res Virol. 1993 May-Jun;144(3):225–231. doi: 10.1016/s0923-2516(06)80033-6. [DOI] [PubMed] [Google Scholar]
  88. Persoons M. C., Daemen M. J., Bruning J. H., Bruggeman C. A. Active cytomegalovirus infection of arterial smooth muscle cells in immunocompromised rats. A clue to herpesvirus-associated atherogenesis? Circ Res. 1994 Aug;75(2):214–220. doi: 10.1161/01.res.75.2.214. [DOI] [PubMed] [Google Scholar]
  89. Pesonen E., Paakkari I., Rapola J. Infection-associated intimal thickening in the coronary arteries of children. Atherosclerosis. 1999 Feb;142(2):425–429. doi: 10.1016/s0021-9150(98)00258-5. [DOI] [PubMed] [Google Scholar]
  90. 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]
  91. Raza-Ahmad A., Klassen G. A., Murphy D. A., Sullivan J. A., Kinley C. E., Landymore R. W., Wood J. R. Evidence of type 2 herpes simplex infection in human coronary arteries at the time of coronary artery bypass surgery. Can J Cardiol. 1995 Dec;11(11):1025–1029. [PubMed] [Google Scholar]
  92. Regnström J., Jovinge S., Båvenholm P., Ericsson C. G., De Faire U., Hamsten A., Hellenius M. L., Nilsson J., Tornvall P. Helicobacter pylori seropositivity is not associated with inflammatory parameters, lipid concentrations and degree of coronary artery disease. J Intern Med. 1998 Feb;243(2):109–113. doi: 10.1046/j.1365-2796.1998.00202.x. [DOI] [PubMed] [Google Scholar]
  93. Ridker P. M., Cushman M., Stampfer M. J., Tracy R. P., Hennekens C. H. Plasma concentration of C-reactive protein and risk of developing peripheral vascular disease. Circulation. 1998 Feb 10;97(5):425–428. doi: 10.1161/01.cir.97.5.425. [DOI] [PubMed] [Google Scholar]
  94. Ridker P. M., Kundsin R. B., Stampfer M. J., Poulin S., Hennekens C. H. Prospective study of Chlamydia pneumoniae IgG seropositivity and risks of future myocardial infarction. Circulation. 1999 Mar 9;99(9):1161–1164. doi: 10.1161/01.cir.99.9.1161. [DOI] [PubMed] [Google Scholar]
  95. Roivainen M., Alfthan G., Jousilahti P., Kimpimäki M., Hovi T., Tuomilehto J. Enterovirus infections as a possible risk factor for myocardial infarction. Circulation. 1998 Dec 8;98(23):2534–2537. doi: 10.1161/01.cir.98.23.2534. [DOI] [PubMed] [Google Scholar]
  96. Shen C. L., Purewal M., San Francisco S., Pence B. C. Absence of PhIP adducts, p53 and Apc mutations, in rats fed a cooked beef diet containing a high level of heterocyclic amines. Nutr Cancer. 1998;30(3):227–231. doi: 10.1080/01635589809514668. [DOI] [PubMed] [Google Scholar]
  97. Shor A., Phillips J. I., Ong G., Thomas B. J., Taylor-Robinson D. Chlamydia pneumoniae in atheroma: consideration of criteria for causality. J Clin Pathol. 1998 Nov;51(11):812–817. doi: 10.1136/jcp.51.11.812. [DOI] [PMC free article] [PubMed] [Google Scholar]
  98. Sinisalo J., Mattila K., Nieminen M. S., Valtonen V., Syrjälä M., Sundberg S., Saikku P. The effect of prolonged doxycycline therapy on Chlamydia pneumoniae serological markers, coronary heart disease risk factors and forearm basal nitric oxide production. J Antimicrob Chemother. 1998 Jan;41(1):85–92. doi: 10.1093/jac/41.1.85. [DOI] [PubMed] [Google Scholar]
  99. Sorlie P. D., Adam E., Melnick S. L., Folsom A., Skelton T., Chambless L. E., Barnes R., Melnick J. L. Cytomegalovirus/herpesvirus and carotid atherosclerosis: the ARIC Study. J Med Virol. 1994 Jan;42(1):33–37. doi: 10.1002/jmv.1890420107. [DOI] [PubMed] [Google Scholar]
  100. Span A. H., Van Boven C. P., Bruggeman C. A. The effect of cytomegalovirus infection on the adherence of polymorphonuclear leucocytes to endothelial cells. Eur J Clin Invest. 1989 Dec;19(6):542–548. doi: 10.1111/j.1365-2362.1989.tb00272.x. [DOI] [PubMed] [Google Scholar]
  101. Span A. H., van Dam-Mieras M. C., Mullers W., Endert J., Muller A. D., Bruggeman C. A. The effect of virus infection on the adherence of leukocytes or platelets to endothelial cells. Eur J Clin Invest. 1991 Jun;21(3):331–338. doi: 10.1111/j.1365-2362.1991.tb01378.x. [DOI] [PubMed] [Google Scholar]
  102. Speir E., Yu Z. X., Ferrans V. J., Huang E. S., Epstein S. E. Aspirin attenuates cytomegalovirus infectivity and gene expression mediated by cyclooxygenase-2 in coronary artery smooth muscle cells. Circ Res. 1998 Jul 27;83(2):210–216. doi: 10.1161/01.res.83.2.210. [DOI] [PubMed] [Google Scholar]
  103. Stille W., Dittmann R. Arteriosklerose als Folge einer chronischen Infektion durch Chlamydia pneumoniae. Herz. 1998 May;23(3):185–192. doi: 10.1007/BF03044604. [DOI] [PubMed] [Google Scholar]
  104. Straka F., Málek I., Stanek V., Ouhrabková R., Gebauerová M., Urbanová D., Vrubel J., Pirk J., Zelízko M., Lánská V. Koronární nemoc u pacientů po transplantaci srdce. Cor Vasa. 1993;35(6):267–275. [PubMed] [Google Scholar]
  105. Tiran A., Tio R. A., Oostenveld E., Harmsen M. C., Tiran B., Den Heijer P., Monnink S. H., Wilders-Truschnig M. M., The T. H. Humoral immune response to human cytomegalovirus in patients undergoing percutaneous transluminal coronary angioplasty. Clin Diagn Lab Immunol. 1999 Jan;6(1):45–49. doi: 10.1128/cdli.6.1.45-49.1999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  106. Tiran A., Tio R. A., Ossewaarde J. M., Tiran B., den Heijer P., The T. H., Wilders-Truschnig M. M. Coronary angioplasty induces rise in Chlamydia pneumoniae-specific antibodies. J Clin Microbiol. 1999 Apr;37(4):1013–1017. doi: 10.1128/jcm.37.4.1013-1017.1999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  107. Torzewski J., Torzewski M., Bowyer D. E., Fröhlich M., Koenig W., Waltenberger J., Fitzsimmons C., Hombach V. C-reactive protein frequently colocalizes with the terminal complement complex in the intima of early atherosclerotic lesions of human coronary arteries. Arterioscler Thromb Vasc Biol. 1998 Sep;18(9):1386–1392. doi: 10.1161/01.atv.18.9.1386. [DOI] [PubMed] [Google Scholar]
  108. Vercellotti G. M. Effects of viral activation of the vessel wall on inflammation and thrombosis. Blood Coagul Fibrinolysis. 1998 Apr;9 (Suppl 2):S3–S6. [PubMed] [Google Scholar]
  109. Visser M. R., Jacob H. S., Goodman J. L., McCarthy J. B., Furcht L. T., Vercellotti G. M. Granulocyte-mediated injury to herpes simplex virus-infected human endothelium. Lab Invest. 1989 Feb;60(2):296–304. [PubMed] [Google Scholar]
  110. Visser M. R., Vercellotti G. M. Herpes simplex virus and atherosclerosis. Eur Heart J. 1993 Dec;14 (Suppl K):39–42. [PubMed] [Google Scholar]
  111. Visseren F. L., Bouter K. P., Pon M. J., Hoekstra J. B., Erkelens D. W., Diepersloot R. J. Patients with diabetes mellitus and atherosclerosis; a role for cytomegalovirus? Diabetes Res Clin Pract. 1997 Apr;36(1):49–55. doi: 10.1016/s0168-8227(97)00027-2. [DOI] [PubMed] [Google Scholar]
  112. Yamashiroya H. M., Ghosh L., Yang R., Robertson A. L., Jr Herpesviridae in the coronary arteries and aorta of young trauma victims. Am J Pathol. 1988 Jan;130(1):71–79. [PMC free article] [PubMed] [Google Scholar]
  113. Yamashita K., Ouchi K., Shirai M., Gondo T., Nakazawa T., Ito H. Distribution of Chlamydia pneumoniae infection in the athersclerotic carotid artery. Stroke. 1998 Apr;29(4):773–778. doi: 10.1161/01.str.29.4.773. [DOI] [PubMed] [Google Scholar]
  114. Yonemitsu Y., Kaneda Y., Komori K., Hirai K., Sugimachi K., Sueishi K. The immediate early gene of human cytomegalovirus stimulates vascular smooth muscle cell proliferation in vitro and in vivo. Biochem Biophys Res Commun. 1997 Feb 13;231(2):447–451. doi: 10.1006/bbrc.1997.6035. [DOI] [PubMed] [Google Scholar]
  115. Yonemitsu Y., Komori K., Sueishi K., Sugimachi K. [Possible role of cytomegalovirus infection in the pathogenesis of human vascular diseases]. Nihon Rinsho. 1998 Jan;56(1):102–108. [PubMed] [Google Scholar]

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

RESOURCES