From the University of Utah, LDS Hospital, Salt Lake City, Utah.
Correspondence to Joseph B. Muhlestein, MD, Assistant Professor of Medicine, University of Utah, LDS Hospital, 8th Ave & C St, Salt Lake City, UT 84143.
Background—Chlamydia
pneumoniae infection has been associated with
atherosclerosis by serological studies and detection of
bacterial antigen within plaque. We sought to evaluate a possible
causal role in an animal model.
Methods and Results—Thirty New Zealand White rabbits were given
three separate intranasal inoculations of either C
pneumoniae (n=20) or saline (n=10) at 3-week intervals and fed
chow enriched with a small amount (0.25%) of cholesterol.
Immediately after the final inoculation, infected and control rabbits
were randomized and begun on a 7-week course of azithromycin or no
therapy. Three months after the final inoculation, rabbits were
euthanatized and sections of thoracic aortas were blindly evaluated
microscopically for maximal intimal thickness (MIT), percentage of
luminal circumference involved (PLCI), and plaque area index (PAI) of
atherosclerosis. Vascular chlamydial antigen was
assessed by direct immunofluorescence. MIT differed
among treatment groups (P=.009), showing an increase in
infected rabbits (0.55 mm; SE=0.15 mm) compared with
uninfected controls (0.16 mm; SE=0.06 mm) and with infected
rabbits receiving antibiotics (0.20 mm; SE=0.03 mm) (both
P<.025), whereas MIT in infected/treated versus control
rabbits did not differ. PLCI also tended to differ
(P<.1) and PAI differed significantly
(P<.01) among groups with a similar pattern. Chlamydial
antigen was detected in 2 untreated, 3 treated, and 0 control
animals.
Conclusions—Intranasal C pneumoniae infection
accelerates intimal thickening in rabbits given a modestly
cholesterol-enhanced diet. In addition, weekly treatment
with azithromycin after infectious exposure prevents accelerated
intimal thickening. These findings strengthen the etiologic link
between C pneumoniae and atherosclerosis
and should stimulate additional animal and human studies, including
clinical antibiotic trials.
© 1998 American Heart Association, Inc.
Brief Rapid Communications
Infection With Chlamydia pneumoniae Accelerates the Development of Atherosclerosis and Treatment With Azithromycin Prevents It in a Rabbit Model
Key Words: atherosclerosis • azithromycin • Chlamydia pneumoniae
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O. J. de Boer, A. C. van der Wal, M. A. Houtkamp, J. M. Ossewaarde, P. Teeling, and A. E. Becker Unstable atherosclerotic plaques contain T-cells that respond to Chlamydia pneumoniae Cardiovasc Res, December 1, 2000; 48(3): 402 - 408. [Abstract] [Full Text] [PDF]
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J. T. Grayston Secondary Prevention Antibiotic Treatment Trials for Coronary Artery Disease Circulation, October 10, 2000; 102(15): 1742 - 1743. [Full Text] [PDF]
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J. B. Muhlestein, J. L. Anderson, J. F. Carlquist, K. Salunkhe, B. D. Horne, R. R. Pearson, T. J. Bunch, A. Allen, S. Trehan, and C. Nielson Randomized Secondary Prevention Trial of Azithromycin in Patients With Coronary Artery Disease : Primary Clinical Results of the ACADEMIC Study Circulation, October 10, 2000; 102(15): 1755 - 1760. [Abstract] [Full Text] [PDF]
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S A Morre, W Stooker, W K Lagrand, A J C van den Brule, and H W M Niessen Microorganisms in the aetiology of atherosclerosis J. Clin. Pathol., September 1, 2000; 53(9): 647 - 654. [Abstract] [Full Text] [PDF]
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P. Liuba, P. Karnani, E. Pesonen, I. Paakkari, A. Forslid, L. Johansson, K. Persson, T. Wadstrom, and R. Laurini Endothelial Dysfunction After Repeated Chlamydia pneumoniae Infection in Apolipoprotein E-Knockout Mice Circulation, August 29, 2000; 102(9): 1039 - 1044. [Abstract] [Full Text] [PDF]
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M. Mayr, S. Kiechl, J. Willeit, G. Wick, and Q. Xu 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, August 22, 2000; 102(8): 833 - 839. [Abstract] [Full Text] [PDF]
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E. Blessing, T.-M. Lin, L. A. Campbell, M. E. Rosenfeld, D. Lloyd, and C.-c. Kuo Chlamydia pneumoniae Induces Inflammatory Changes in the Heart and Aorta of Normocholesterolemic C57BL/6J Mice Infect. Immun., August 1, 2000; 68(8): 4765 - 4768. [Abstract] [Full Text] [PDF]
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 W. Koenig Heart disease and the inflammatory response BMJ, July 22, 2000; 321(7255): 187 - 188. [Full Text]
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 I. W. Fong Emerging relations between infectious diseases and coronary artery disease and atherosclerosis Can. Med. Assoc. J., July 1, 2000; 163(1): 49 - 56. [Abstract] [Full Text] [PDF]
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J. B. Mahony, S. Chong, B. K. Coombes, M. Smieja, and A. Petrich Analytical Sensitivity, Reproducibility of Results, and Clinical Performance of Five PCR Assays for Detecting Chlamydia pneumoniae DNA in Peripheral Blood Mononuclear Cells J. Clin. Microbiol., July 1, 2000; 38(7): 2622 - 2627. [Abstract] [Full Text]
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A.J. Camm and K.M. Fox Chlamydia pneumonia (and other infective agents) in atherosclerosis and acute coronary syndromes. How good is the evidence? Eur. Heart J., July 1, 2000; 21(13): 1046 - 1051. [PDF]
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M. S. V. Elkind, I-F. Lin, J. T. Grayston, and R. L. Sacco Chlamydia pneumoniae and the Risk of First Ischemic Stroke : The Northern Manhattan Stroke Study Stroke, July 1, 2000; 31(7): 1521 - 1525. [Abstract] [Full Text] [PDF]
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K. Ericson, T. G. P. Saldeen, O. Lindquist, C. Pahlson, and J. L. Mehta Relationship of Chlamydia pneumoniae Infection to Severity of Human Coronary Atherosclerosis Circulation, June 6, 2000; 101(22): 2568 - 2571. [Abstract] [Full Text] [PDF]
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D. P. Hajjar Oxidized Lipoproteins and Infectious Agents : Are They in Collusion to Accelerate Atherogenesis? Arterioscler Thromb Vasc Biol, June 1, 2000; 20(6): 1421 - 1422. [Full Text] [PDF]
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M. E. Rottenberg, A. Gigliotti Rothfuchs, D. Gigliotti, M. Ceausu, C. Une, V. Levitsky, and H. Wigzell Regulation and Role of IFN-{gamma} in the Innate Resistance to Infection with Chlamydia pneumoniae J. Immunol., May 1, 2000; 164(9): 4812 - 4818. [Abstract] [Full Text] [PDF]
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E. Gurfinkel, G. Bozovich, B. Mautner, J. L. Anderson, J. B. Muhlestein, J. Carlquist, A. Allen, S. Trehan, C. Nielson, S. Hall, et al. Chlamydia pneumoniae in Coronary Artery Disease • Response Circulation, March 28, 2000; 101 (12): e118 - e119. [Full Text] [PDF]
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A. Hoffmeister, D. Rothenbacher, P. Wanner, G. Bode, K. Persson, H. Brenner, V. Hombach, and W. Koenig Seropositivity to chlamydial lipopolysaccharide and chlamydia pneumoniae, systemic inflammation and stable coronary artery disease: Negative results of a case-control study J. Am. Coll. Cardiol., January 1, 2000; 35(1): 112 - 118. [Abstract] [Full Text] [PDF]
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I. M. Loftus, A. R. Naylor, S. Goodall, M. Crowther, L. Jones, P. R. F. Bell, and M. M. Thompson Increased Matrix Metalloproteinase-9 Activity in Unstable Carotid Plaques : A Potential Role in Acute Plaque Disruption Stroke, January 1, 2000; 31(1): 40 - 47. [Abstract] [Full Text] [PDF]
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 T. Quaschning and C. Wanner The role of Chlamydia in coronary heart disease--fact or fiction? Nephrol. Dial. Transplant., December 1, 1999; 14(12): 2800 - 2803. [Full Text] [PDF]
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A. Shor and J. I. Phillips Chlamydia pneumoniae and Atherosclerosis JAMA, December 1, 1999; 282(21): 2071 - 2073. [Full Text] [PDF]
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I. W. Fong, B. Chiu, E. Viira, D. Jang, M. W. Fong, R. Peeling, and J. B. Mahony Can an Antibiotic (Macrolide) Prevent Chlamydia pneumoniae-Induced Atherosclerosis in a Rabbit Model? Clin. Vaccine Immunol., November 1, 1999; 6(6): 891 - 894. [Abstract] [Full Text] [PDF]
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I. W. Fong, B. Chiu, E. Viira, D. Jang, and J. B. Mahony De Novo Induction of Atherosclerosis by Chlamydia pneumoniae in a Rabbit Model Infect. Immun., November 1, 1999; 67(11): 6048 - 6055. [Abstract] [Full Text] [PDF]
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Y.-k. Wong, K. D. Dawkins, and M. E. Ward Circulating chlamydia pneumoniae DNA as a predictor of coronary artery disease J. Am. Coll. Cardiol., November 1, 1999; 34(5): 1435 - 1439. [Abstract] [Full Text] [PDF]
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 J. T. Grayston Does Chlamydia pneumoniae Cause Atherosclerosis? Arch Surg, September 1, 1999; 134(9): 930 - 934. [Full Text] [PDF]
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S. E. Epstein, Y. F. Zhou, and J. Zhu Infection and Atherosclerosis : Emerging Mechanistic Paradigms Circulation, July 27, 1999; 100 (4): e20 - e28. [Abstract] [Full Text] [PDF]
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B. K. Coombes and J. B. Mahony Chlamydia pneumoniae Infection of Human Endothelial Cells Induces Proliferation of Smooth Muscle Cells via an Endothelial Cell-Derived Soluble Factor(s) Infect. Immun., June 1, 1999; 67(6): 2909 - 2915. [Abstract] [Full Text] [PDF]
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M. Thomas, Y. Wong, D. Thomas, M. Ajaz, V. Tsang, P. J. Gallagher, and M. E. Ward Relation Between Direct Detection of Chlamydia pneumoniae DNA in Human Coronary Arteries at Postmortem Examination and Histological Severity (Stary Grading) of Associated Atherosclerotic Plaque Circulation, June 1, 1999; 99(21): 2733 - 2736. [Abstract] [Full Text] [PDF]
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J. T. Grayston Antibiotic Treatment Trials for Secondary Prevention of Coronary Artery Disease Events Circulation, March 30, 1999; 99(12): 1538 - 1539. [Full Text] [PDF]
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 Y-K Wong, P J Gallagher, and M E Ward Chlamydia pneumoniae and atherosclerosis Heart, March 1, 1999; 81(3): 232 - 238. [Abstract] [Full Text]
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