@entity2247 inhibition and inhibition of @entity3901 increase XXXX expression and foam cell formation in @entity1357 cells.

@entity1 @entity1357 @entity12698 @entity583 @entity75 @entity2918 @entity1426 @entity165 @entity3901 @entity25386 @entity2247 @entity4210
Cardiovascular safety of cyclooxygenase (COX)-2-selective inhibitors and nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) is of worldwide concern. @entity2247 inhibitors and NSAIDs act by inhibiting @entity1426 metabolism to @entity2918 . They confer a cardiovascular hazard manifested as an elevated risk of @entity583 . Mechanisms underlying these cardiovascular effects are uncertain. Here we determine whether interference with @entity3901 ( @entity3901 ) or @entity2247 through pharmacologic blockade or silencing RNA impacts expression of scavenger receptor @entity4210 and scavenger receptor A, both involved in @entity165 uptake in monocytes and macrophages. @entity1357 @entity1 monocytes and @entity1 peripheral blood mononuclear cells were exposed to @entity12698 , a @entity2247 selective inhibitor currently in clinical use, and to @entity25386 (AACOCF3), an @entity1426 analog that selectively inhibits @entity3901 . @entity12698 and AACOCF3 each upregulated expression of @entity4210 , but not scavenger receptor A, as determined by quantitative PCR and immunoblotting. Silencing of @entity3901 or @entity2247 had comparable effects to pharmacologic treatments. Oil red O staining revealed a profound increase in foam cell transformation of @entity1357 macrophages exposed to either @entity12698 or AACOCF3 (both 25  M), supporting a role for the COX pathway in maintaining macrophage @entity165 homeostasis. Demonstration of disrupted @entity165 balance by AACOCF3 and @entity12698 provides further evidence of the possible mechanism by which COX inhibition may promote lipid overload leading to @entity75 formation and increased cardiovascular events.
