Nitric oxide synthase plays a role in Chlamydia pneumoniae-induced atherosclerosis.
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.
Chesebro
Brian B
BB
Department of Pathobiology, University of Washington, P.O. Box 357238, Seattle, WA 98195, USA.
Blessing
Erwin
E
Kuo
Cho-Chou
CC
Rosenfeld
Michael E
ME
Puolakkainen
Mirja
M
Campbell
Lee Ann
LA
D000818:Animals; D002690:Chlamydia Infections / Q000201:enzymology*; D016993:Chlamydophila pneumoniae; D003327:Coronary Disease / Q000201:enzymology* / Q000382:microbiology*; D006949:Hyperlipidemias / Q000201:enzymology / Q000382:microbiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D019001:Nitric Oxide Synthase / Q000378:metabolism / Q000502:physiology*; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III
D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496317:Nos2 protein, mouse; C496315:Nos3 protein, mouse