title: The select cyclooxygenase-2 inhibitor celecoxib reduced the extent of atherosclerosis in apo E-/- mice.
abstract: Many investigators have suggested that immune activation may trigger the atherosclerotic process. The benefits of aspirin in preventing myocardial infarction have been attributed, in part, to its anti-inflammatory effects. Several reports have documented that cyclooxygenase (COX)-2 is up-regulated in human and mouse atherosclerotic lesions. To clarify the role of COX-2 in atherosclerosis, we conducted a study to test whether the COX-2 inhibitor, celecoxib, prevents the development and progression of the atherosclerotic process. We have used the apo E-/- mouse, a relevant animal model of atherosclerosis that develops fibrofatty lesions similar to human atherosclerosis. Treatment of 4-wk old apo E-/- mice with a standard rodent no. 5020 diet supplemented with 900 ppm of celecoxib for 16 wk led to an 81% reduction in lesion size. The mean lesion area per section (mean +/- SD) of proximal aorta from the apo E-/- mice fed the diet with celecoxib (33,991 +/- 7863 microm2, P < 0.001) was significantly less than that of the untreated apo E-/- mice (183,401 +/- 36,212 microm2). There were no lesions detected in the C57B1/6 mice. Immunohistochemistry of the ileum revealed that there was 80% reduction in staining for intercellular adhesion molecule and 60% reduction in staining for vascular cell adhesion molecule in the celecoxib treated mice. The protective effect of celecoxib was not maintained when the mice were switched after feeding the celecoxib-supplemented diet to the control 5020 diet for an additional 10 wk. These findings demonstrate that selective inhibition of the COX-2 enzyme with celecoxib prevented the development of atherosclerotic lesions in the proximal aortas from apo E-/- mice. One of the possible mechanisms is reduction in expression of the endothelial cell adhesion cell molecules intercellular adhesion molecule and vascular cell adhesion molecule, which plays a key role in the recruitment of inflammatory cells during the early stages of atherogenesis.
authors.affiliation: Department of Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
authors.forename: Shushan
authors.initials: S
authors.lastname: Jacob
authors.forename: Lisa
authors.initials: L
authors.lastname: Laury-Kleintop
authors.forename: Susan
authors.initials: S
authors.lastname: Lanza-Jacoby
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism*; D050197:Atherosclerosis / Q000188:drug therapy* / Q000378:metabolism* / Q000517:prevention & control; D000068579:Celecoxib; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D018450:Disease Progression; D007082:Ileum / Q000378:metabolism / Q000473:pathology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011720:Pyrazoles / Q000494:pharmacology* / Q000627:therapeutic use; D013449:Sulfonamides / Q000494:pharmacology* / Q000627:therapeutic use; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D051546:Cyclooxygenase 2; D000068579:Celecoxib