title: Nitric oxide synthase plays a role in Chlamydia pneumoniae-induced atherosclerosis.
abstract: 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.
authors.affiliation: Department of Pathobiology, University of Washington, P.O. Box 357238, Seattle, WA 98195, USA.
authors.forename: Brian B
authors.initials: BB
authors.lastname: Chesebro
authors.forename: Erwin
authors.initials: E
authors.lastname: Blessing
authors.forename: Cho-Chou
authors.initials: CC
authors.lastname: Kuo
authors.forename: Michael E
authors.initials: ME
authors.lastname: Rosenfeld
authors.forename: Mirja
authors.initials: M
authors.lastname: Puolakkainen
authors.forename: Lee Ann
authors.initials: LA
authors.lastname: Campbell
mesh_terms: 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
chemical_list: D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496317:Nos2 protein, mouse; C496315:Nos3 protein, mouse