Celecoxib Combined with Atorvastatin Prevents Progression of Atherosclerosis

BackgroundIncreased 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.Materials and MethodsApo 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.ResultsWhen 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) E2, 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).ConclusionThis 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.