Celecoxib combined with atorvastatin prevents progression of atherosclerosis.
BACKGROUND
Increased expression of cyclooxygenase (COX-2) contributes to atherosclerosis. Recent studies suggest that COX-2 inhibitors prevent early plaque development but their effects on established lesions are less clear, while the statins promote plaque stability. The purpose of this study is to investigate whether administering a combination of a COX-2 inhibitor with a statin drug alters plaque progression in apo E-/- mice.


METHODS
Apo E-/- mice were fed a Western diet from 6 to 26 wk of age. At 26 wk, the Western diets supplemented with atorvastatin, celecoxib, or atorvastatin plus celecoxib were given for an additional 12 wk.


RESULTS
When the mice were 38 wk of age, the total area occupied by the atherosclerotic lesion was 53% less in the mice fed the combination of atorvastatin + celecoxib P ≤ 0.05) than that of the apo E-/- mice fed the Western diet alone, atorvastatin alone, or celecoxib alone. The decreased extent of atherosclerosis observed in the apo E-/- mice fed the combination of drugs was associated with reduced levels of prostaglandin (PG) E(2,) decreased protein expression of metalloproteinase (MMP)-9, macrophage chemotactic protein (MCP-1), and COX 2, and decreased staining for MMP-9, F4-80 (a marker for macrophages), and vascular cell adhesion molecule (VCAM).


CONCLUSIONS
This study indicates that using statins with a COX-2 inhibitor reduced the extent of atherosclerosis and inflammatory/cell adhesion molecule levels in the apo E-/- mouse model.
Department of Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania 19017, USA.
Mihir
M
Raval
Philippe G
PG
Frank
Lisa
L
Laury-Kleintop
Guang
G
Yan
Susan
S
Lanza-Jacoby
D000818:Animals; D001057:Apolipoproteins E / Q000502:physiology; D050197:Atherosclerosis / Q000188:drug therapy*; D000069059:Atorvastatin; D000068579:Celecoxib; D018932:Chemokine CCL2 / Q000097:blood; D051546:Cyclooxygenase 2 / Q000097:blood; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage*; D015232:Dinoprostone / Q000097:blood; D018450:Disease Progression; D004359:Drug Therapy, Combination; D006538:Heptanoic Acids / Q000008:administration & dosage*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D007150:Immunohistochemistry; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D011720:Pyrazoles / Q000008:administration & dosage*; D011758:Pyrroles / Q000008:administration & dosage*; D013449:Sulfonamides / Q000008:administration & dosage*; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics
D001057:Apolipoproteins E; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D052246:Cyclooxygenase 2 Inhibitors; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011720:Pyrazoles; D011758:Pyrroles; D013449:Sulfonamides; D019010:Vascular Cell Adhesion Molecule-1; D000069059:Atorvastatin; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D020780:Matrix Metalloproteinase 9; D000068579:Celecoxib; D015232:Dinoprostone