title: Chronic inhibition of cyclooxygenase-2 does not alter plaque composition in a mouse model of advanced unstable atherosclerosis.
abstract: OBJECTIVE
  Inflammation contributes to atherosclerotic plaque initiation and progression. Recent studies suggest that anti-inflammatory drugs such as cyclooxygenase-2 (Cox-2) inhibitors have anti-atherogenic effects. The current study was designed to investigate whether administration of a Cox-2 inhibitor to older apolipoprotein E deficient (apo E-/-) mice with established lesions alters the composition and increases the stability of the lesions.
  
  
  RESULTS
  The Cox-2 inhibitor Celecoxib was administered in chow to 26-week-old, male, apo E-/- mice exhibiting advanced, unstable atherosclerotic lesions within the innominate/brachiocephalic artery. Mice administered Celecoxib had no significant changes in serum cholesterol or the average cross sectional area of atherosclerotic lesion in the innominate artery after 15 weeks of treatment in comparison to non-treated control mice. Histological analyses of sections of the innominate artery demonstrated no significant changes in the frequency of markers of advanced and unstable atherosclerotic plaques, including intra-plaque hemorrhage, vascular calcification, thinning of the fibrous cap, size of the necrotic core and macrophage content. There were also no significant differences in the content of Cox-2 within the lesions. Quantitative real time polymerase chain reaction with mRNA isolated from the aorta of each mouse revealed no significant changes in the expression of tissue factor and inducible nitric oxide synthase. However, mRNA levels for MCP-1 were increased fivefold following 15 weeks of treatment with Celecoxib in comparison to non-treated control mice.
  
  
  CONCLUSIONS
  These data suggest that Celecoxib has no effect on the composition of advanced atherosclerotic lesions in older apo E-/- mice.
authors.affiliation: Department of Pathobiology and the Interdisciplinary Graduate Program in Nutritional Sciences, University of Washington, Seattle, WA 98195, USA.
authors.forename: Florian
authors.initials: F
authors.lastname: Bea
authors.forename: Erwin
authors.initials: E
authors.lastname: Blessing
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Bennett
authors.forename: Cho Chou
authors.initials: CC
authors.lastname: Kuo
authors.forename: Lee Ann
authors.initials: LA
authors.lastname: Campbell
authors.forename: Jörg
authors.initials: J
authors.lastname: Kreuzer
authors.forename: Michael E
authors.initials: ME
authors.lastname: Rosenfeld
mesh_terms: D000199:Actins / Q000235:genetics; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001057:Apolipoproteins E / Q000235:genetics; D001161:Arteriosclerosis / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D016122:Brachiocephalic Trunk / Q000201:enzymology / Q000473:pathology; D000068579:Celecoxib; D018932:Chemokine CCL2 / Q000235:genetics; D002784:Cholesterol / Q000097:blood; D051546:Cyclooxygenase 2; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D019001:Nitric Oxide Synthase / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011720:Pyrazoles; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013449:Sulfonamides / Q000627:therapeutic use*; D013925:Thromboplastin / Q000235:genetics; D017211:Treatment Failure
chemical_list: D000199:Actins; D000893:Anti-Inflammatory Agents; D001057:Apolipoproteins E; D018932:Chemokine CCL2; D007527:Isoenzymes; D011720:Pyrazoles; D013449:Sulfonamides; D013925:Thromboplastin; D002784:Cholesterol; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D000068579:Celecoxib