© 2003 by European Society of Cardiology
Copyright © 2003, European Society of Cardiology
Nitric oxide synthase plays a role in Chlamydia pneumoniae-induced atherosclerosis
Department of Pathobiology, University of Washington, P.O. Box 357238, Seattle, WA 98195, USA
*Corresponding author. Tel.: +1-206-543-0317; fax: +1-206-543-3873. Email address: bchesebr{at}mail.jhmi.edu, lacamp{at}u.washington.edu
Objective: Chlamydia pneumoniae infection has been associated with atherosclerosis, although the mechanisms by which C. pneumoniae contribute to atherogenesis remain unclear. Altered production of nitric oxide, a known bactericidal and anti-inflammatory agent, represents one possible mechanistic link. To examine this issue, a diet-induced, hyperlipidemic mouse model of early atherosclerosis was used. Methods: A series of intranasal inoculations of C. pneumoniae strain AR-39 were administered to mice lacking endothelial or inducible nitric oxide synthase and to normal controls. After 18 weeks on an atherogenic diet, atherosclerotic lesion area in the aortic sinus was measured using computer-assisted morphometry. Results: In the absence of C. pneumoniae infection, diet-fed eNOS–/– mice developed enlarged fatty streak lesions of borderline significance in comparison to uninfected, wild-type mice, while the lesion area in uninfected, diet-fed iNOS–/– mice did not differ significantly from lesion area in wild-type animals. In contrast, lesion area in infected eNOS–/– mice increased slightly, but not significantly in comparison to uninfected eNOS–/– mice. Lesion area in the infected iNOS–/– mice was significantly enlarged when compared to both uninfected iNOS–/– mice as well as to infected wild-type mice. Conclusions: These data suggest that production of nitric oxide by eNOS protects against development of fatty streak lesions in uninfected hyperlipidemic mice, but does not offer additional protection in infected hyperlipidemic mice, while iNOS may play a protective role, thus limiting chlamydial exacerbation of fatty streak lesions.
KEYWORDS Infection/inflammation; Atherosclerosis; Nitric oxide; Histopathology; Coronary artery disease
1 Current address: School of Medicine, Johns Hopkins University, Baltimore, MD 21287. USA.
2 Current address: Ruprecht-Karl-Universitat Heidelberg, Bergheimer Strasse 58, 69115 Heidelberg, Germany.
3 Current address: University of Helsinki, Haartman Institute, Department of Virology, P.O. Box 21 (Haartmaninkatu 3), 00014 University of Helsinki, Finland.
Time for primary review 34 days.
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