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Chlamydia pneumoniae infection significantly exacerbates aortic atherosclerosis in an LDLR–/– mouse model within six months

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Abstract

We have previously shown that infection with the C. pneumoniae AR39 strain once monthly for 9 consecutive months significantly exacerbated atherosclerosis in mice with LDL receptor deficiency (LDLR–/–) in the presence of a high cholesterol diet. To further optimize the LDLR–/– mouse model for studying the mechanisms of C. pneumoniae atherogenesis, we have tested a different infection protocol with intranasal inoculation twice monthly for 6 consecutive months in the present study. We found that C. pneumoniae infection for 6 months was sufficient to produce a 130%, significantly greater exacerbation of aortic atherosclerosis in LDLR–/– mice in the presence of a high cholesterol diet. Mice receiving a high cholesterol diet alone displayed a lesion area index of 18.2 ± 6.1 (S.D.) while mice treated with both the high cholesterol diet and C. pneumoniae infection had a lesion area index of 41.8 ± 15.2 (S.D.). However, the chlamydial infection did not significantly alter the mouse serum total cholesterol or the LDL levels induced by the high cholesterol diet. This study not only confirms our previous findings that C. pneumoniae infection can exacerbate aortic atherosclerosis lesion in the LDLR–/– mice, but also further optimizes the LDLR–/– mouse model for future mechanism studies.

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References

  1. Moazed TC, Campbell LA, Rosenfeld ME, Grayston JT, Kuo CC: Chlamydia pneumoniae infection accelerates the progression of atherosclerosis in apolipoprotein E-deficient mice. J Infect Dis 180: 238–241, 1999

    Google Scholar 

  2. Campbell LA, Kuo CC, Grayston JT: Chlamydia pneumoniae and cardiovascular disease. Emerg Infect Dis 4: 571–579, 1998

    Google Scholar 

  3. Grayston JT, Kuo CC, Campbell LA, Wang SP, Jackson LA: Chlamydia pneumoniae and cardiovascular disease. Cardiologia 42: 1145–1151, 1997

    Google Scholar 

  4. Saikku P: Chlamydia pneumoniae and atherosclerosis–an update. Scand J Infect Dis 104(suppl): 53–56, 1997

    Google Scholar 

  5. Kuo C, Campbell LA: Is infection with Chlamydia pneumoniae a causative agent in atherosclerosis? Mol Med Today 4: 426–430, 1998

    Google Scholar 

  6. Byrne GI, Kalayoglu MV: Chlamydia pneumoniae and atherosclerosis: Links to the disease process. Am Heart J 138: S488–S490, 1999

    Google Scholar 

  7. Ong G, Thomas BJ, Mansfield AO, Davidson BR, Taylor-Robinson D: Detection and widespread distribution of Chlamydia pneumoniae in the vascular system and its possible implications. J Clin Pathol 49: 102–106, 1996

    Google Scholar 

  8. Kuo CC, Grayston JT, Campbell LA, Goo YA, Wissler RW, Benditt EP: Chlamydia pneumoniae (TWAR) in coronary arteries of young adults (15–34 years old). Proc Natl Acad Sci USA 92: 6911–6914, 1995

    Google Scholar 

  9. 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 125: 979–982, 1996

    Google Scholar 

  10. Saikku P, Leinonen M, Mattila K, Ekman MR, Nieminen MS, Makela PH, Huttunen JK, Valtonen V: Serological evidence of an association of a novel Chlamydia, TWAR, with chronic coronary heart disease and acute myocardial infarction. Lancet 2: 983–986, 1988

    Google Scholar 

  11. Puolakkainen M, Kuo CC, Shor A, Wang SP, Grayston JT, Campbell LA: Serological response to Chlamydia pneumoniae in adults with coronary arterial fatty streaks and fibrolipid plaques. J Clin Microbiol 31: 2212–2214, 1993

    Google Scholar 

  12. Kalayoglu MV, Hoerneman B, LaVerda D, Morrison SG, Morrison RP, Byrne GI: Cellular oxidation of low-density lipoprotein by Chlamydia pneumoniae. J Infect Dis 180: 780–790, 1998

    Google Scholar 

  13. Kalayoglu MV, Byrne GI: Induction of macrophage foam cell formation by Chlamydia pneumoniae. J Infect Dis 177: 725–729, 1998

    Google Scholar 

  14. Kalayoglu MV, Byrne GI: A Chlamydia pneumoniae component that induces macrophage foam cell formation is chlamydial lipopolysaccharide. Infect Immun 66: 5067–5072, 1998

    Google Scholar 

  15. Muhlestein JB, Anderson JL, Hammond EH, Zhao L, Trehan S, Schwobe EP, Carlquist JF: Infection with Chlamydia pneumoniae accelerates the development of atherosclerosis and treatment with azithromycin prevents it in a rabbit model. Circulation 97: 633–636, 1998

    Google Scholar 

  16. Fong IW, Chiu B, Viira E, Fong MW, Jang D, Mahony J: Rabbit model for Chlamydia pneumoniae infection. J Clin Microbiol 35: 48–52, 1997

    Google Scholar 

  17. Hu H, Pierce GN, Zhong G: The atherogenic effects of chlamydia are dependent on serum cholesterol and specific to Chlamydia pneumoniae. J Clin Invest 103: 747–753, 1999

    Google Scholar 

  18. Grayston JT, Kuo CC, Wang SP, Altman J: A new Chlamydia psittaci strain, TWAR, isolated in acute respiratory tract infections. N Engl J Med 315: 161–168, 1986

    Google Scholar 

  19. Palinski W, Tangirala RK, Miller E, Young SG, Witztum JL: Increased autoantibody titers against epitopes of oxidized LDL in LDL receptor-deficient mice with increased atherosclerosis. Arterioscler Thromb Vasc Biol 15: 1569–1576, 1995

    Google Scholar 

  20. Zhong G, Toth I, Reid R, Brunham RC: Immunogenicity evaluation of a lipidic amino acid-based synthetic peptide vaccine for Chlamydia trachomatis. J Immunol 151: 3728–3736, 1993

    Google Scholar 

  21. Aji W, Ravalli S, Szabolcs M, Jiang XC, Sciacca RR, Michler RE, Cannon PJ: L-arginine prevents xanthoma development and inhibits atherosclerosis in LDL receptor knockout mice (see comments). Circulation 95: 430–437, 1997

    Google Scholar 

  22. Roselaar SE, Kakkanathu PX, Daugherty A: Lymphocyte populations in atherosclerotic lesions of apoE–/–and LDL receptor–/–mice. Decreasing density with disease progression. Arterioscler Thromb Vasc Biol 16: 1013–1018, 1996

    Google Scholar 

  23. Iiyama K, Hajra L, Iiyama M, Li H, DiChiara M, Medoff BD, Cybulsky MI: Patterns of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 expression in rabbit and mouse atherosclerotic lesions and at sites predisposed to lesion formation. Circ Res 85: 199–207, 1996

    Google Scholar 

  24. Hofker MH, van Vlijmen BJ, Havekes LM: Transgenic mouse models to study the role of APOE in hyperlipidemia and atherosclerosis. Atherosclerosis 137: 1–11, 1998

    Google Scholar 

  25. Campbell LA, Kuo C: Mouse models of Chlamydia pneumoniae infection and atherosclerosis. Am Heart J 138: S516–S518, 1999

    Google Scholar 

  26. Bird DA, Tangirala RK, Fruebis J, Steinberg D, Witztum JL, Palinski W: Effect of probucol on LDL oxidation and atherosclerosis in LDL receptor-deficient mice (in process citation). J Lipid Res 39: 1079–1090, 1998

    Google Scholar 

  27. Plump AS, Masucci-Magoulas L, Bruce C, Bisgaier CL, Breslow JL, Tall AR: Increased atherosclerosis in ApoE and LDL receptor gene knock-out mice as a result of human cholesteryl ester transfer protein transgene expression. Arterioscler Thromb Vasc Biol 19: 1105–1110, 1999

    Google Scholar 

  28. Gupta S, Pablo AM, Jiang X, Wang N, Tall AR, Schindler C: IFN-gamma potentiates atherosclerosis in ApoE knock-out mice. J Clin Invest 99: 2752–2761, 1997

    Google Scholar 

  29. Mach F, Schonbeck U, Sukhova GK, Atkinson E, Libby P: Reduction of atherosclerosis in mice by inhibition of CD40 signalling. Nature 394: 200–203, 1998

    Google Scholar 

  30. Lutgens E, Gorelik L, Daemen MJ, de Muinck ED, Grewal IS, Koteliansky VE, Flavell RA: Requirement for CD154 in the progression of atherosclerosis. Nat Med 5: 1313–1316, 1999

    Google Scholar 

  31. Aiello RJ, Bourassa PA, Lindsey S, Weng W, Natoli E, Rollins BJ, Milos PM: Monocyte chemoattractant protein-1 accelerates atherosclerosis in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol 19: 1518–1525, 1999

    Google Scholar 

  32. Dawson TC, Kuziel WA, Osahar TA, Maeda N: Absence of CC chemokine receptor-2 reduces atherosclerosis in apolipoprotein E-deficient mice. Atherosclerosis 143: 205–211, 1999

    Google Scholar 

  33. Gu L, Okada Y, Clinton SK, Gerard C, Sukhova GK, Libby P, Rollins BJ: Absence of monocyte chemoattractant protein-1 reduces atherosclerosis in low density lipoprotein receptor-deficient mice. Mol Cell 2: 275–281, 1998

    Google Scholar 

  34. Boring L, Gosling J, Cleary M, Charo IF: Decreased lesion formation in CCR2–/–mice reveals a role for chemokines in the initiation of atherosclerosis. Nature 394: 894–897, 1998

    Google Scholar 

  35. Ross R:Atherosclerosis is an inflammatory disease. Am Heart J 138: S419–S420, 1999

    Google Scholar 

  36. Ross R: Cell biology of atherosclerosis. Annu Rev Physiol 57: 791–804, 1995

    Google Scholar 

  37. Collins RG, Velji R, Guevara NV, Hicks MJ, Chan L, Beaudet AL: P-Selectin or Intercellular Adhesion Molecule (ICAM)-1 deficiency substantially protects against atherosclerosis in apolipoprotein E-deficient mice. J Exp Med 191: 189–194, 2000

    Google Scholar 

  38. Quinn TC, Gaydos CA: In vitro infection and pathogenesis of Chlamydia pneumoniae in endovascular cells. Am Heart J 138: S507–S511, 1999

    Google Scholar 

  39. Rasmussen SJ, Eckmann L, Quayle AJ, Shen L, Zhang YX, Anderson DJ, Fierer J, Stephens RS, Kagnoff MF: Secretion of proinflammatory cytokines by epithelial cells in response to Chlamydia infection suggests a central role for epithelial cells in chlamydial pathogenesis. J Clin Invest 99: 77–87, 1997

    Google Scholar 

  40. Redecke V, Dalhoff K, Bohnet S, Braun J, Maass M: Interaction of Chlamydia pneumoniae and human alveolar macrophages: Infection and inflammatory response. Am J Respir Cell Mol Biol 19: 721–727, 1998

    Google Scholar 

  41. Molestina RE, Dean D, Miller RD, Ramirez JA, Summersgill JT: 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 66: 1370–1376, 1998

    Google Scholar 

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Authors and Affiliations

  1. Departments of Medical Microbiology and Physiology, St. Boniface General Hospital Research Centre, University of Manitoba, R3E 0W3, Canada

    Li Liu, He Hu & Hezhao Ji

  2. Aventis Pasteur Canada, 1755 Steeles Avenue West, North York, Ontario, M2R 3T4, Canada

    Andrew D. Murdin

  3. Division of Stroke and Vascular Disease, St. Boniface General Hospital Research Centre, University of Manitoba, R3E 0W3, Canada

    Grant N. Pierce

  4. Departments of Medical Microbiology and Physiology, and Division of Stroke and Vascular Disease, St. Boniface General Hospital Research Centre, University of Manitoba, R3E 0W3, Canada

    Guangming Zhong

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Liu, L., Hu, H., Ji, H. et al. Chlamydia pneumoniae infection significantly exacerbates aortic atherosclerosis in an LDLR–/– mouse model within six months. Mol Cell Biochem 215, 123–128 (2000). https://doi.org/10.1023/A:1026531506202

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