title: Absence of myeloid COX-2 attenuates acute inflammation but does not influence development of atherosclerosis in apolipoprotein E null mice.
abstract: OBJECTIVE
  The role of myeloid cell cyclooxygenase-2 (COX-2) in the progression of atherosclerosis has not been clearly defined.
  
  
  RESULTS
  We investigated the role of COX-2 expressed in the myeloid lineage in the development of atherosclerosis using a myeloid-specific COX-2(-/-) (COX-2(-M/-M)) mouse on a hyperlipidemic apolipoprotein (apo) E(-/-) background (COX-2(-M/-M)/apoE(-/-)). Myeloid COX-2 depletion resulted in significant attenuation of acute inflammation corresponding with decreased PGE(2) levels in an air pouch model. COX-2 depletion in myeloid cells did not influence development of atherosclerosis in COX-2(-M/-M)/apoE(-/-) when compared to apoE(-/-) littermates fed either chow or western diets. The unanticipated lack of contribution of myeloid COX-2 to the development atherosclerosis is not attributable to altered maintenance, differentiation, or mobilization of myeloid and lymphoid populations. Moreover, myeloid COX-2 depletion resulted in unaltered serum prostanoid levels and cellular composition of atherosclerotic lesions of COX-2(-M/-M)/apoE(-/-) mice.
  
  
  CONCLUSIONS
  Our results suggest that COX-2 expression in myeloid cells, including macrophages, does not influence the development of atherosclerosis in mice.
authors.affiliation: Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Calif 90095, USA.
authors.forename: Ajay J
authors.initials: AJ
authors.lastname: Narasimha
authors.forename: Junji
authors.initials: J
authors.lastname: Watanabe
authors.forename: Tomo-o
authors.initials: TO
authors.lastname: Ishikawa
authors.forename: Saul J
authors.initials: SJ
authors.lastname: Priceman
authors.forename: Lily
authors.initials: L
authors.lastname: Wu
authors.forename: Harvey R
authors.initials: HR
authors.lastname: Herschman
authors.forename: Srinivasa T
authors.initials: ST
authors.lastname: Reddy
mesh_terms: D000818:Animals; D001018:Aortic Diseases / Q000201:enzymology* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D050197:Atherosclerosis / Q000201:enzymology* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000172:deficiency* / Q000235:genetics; D004041:Dietary Fats; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D007249:Inflammation / Q000201:enzymology* / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; D004041:Dietary Fats; D014409:Tumor Necrosis Factor-alpha; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D015232:Dinoprostone