Inhibition of cyclooxygenase-2 improves cardiac function after @entity583 in the XXXX .

@entity13586 @entity10178 @entity63 @entity19 @entity1184 @entity16 @entity24397 @entity1188 @entity299 @entity583 @entity8228
@entity10178 is expressed in the heart in animal models of @entity63 . Recent studies have suggested that @entity10178 products are involved in inflammatory cell infiltration and fibroblast proliferation in the heart. Using a @entity19 model, we questioned whether 1). @entity583 ( @entity583 ) in vivo induces @entity10178 expression chronically, and 2). @entity10178 inhibition reduces collagen content and improves cardiac function in @entity19 with @entity583 . @entity583 was produced by ligation of the left anterior descending coronary artery in @entity19 . Two days later, @entity19 were treated with 3 mg/kg @entity8228 , a selective @entity10178 inhibitor, or vehicle in drinking water for 2 wk. After the treatment period, @entity19 were subjected to two-dimensional M-mode echocardiography to determine cardiac function. Hearts were then analyzed for determination of @entity1188 size, interstitial collagen content, @entity24397 ( @entity24397 ) mRNA, myocyte cross-sectional area, and immunohistochemical staining for transforming growth factor (TGF)-beta and @entity10178 . @entity10178 protein, detected by immunohistochemistry, was increased in @entity583 versus sham hearts. @entity583 resulted in increased left ventricular systolic and diastolic dimension and decreased ejection fraction, fractional shortening, and cardiac output. @entity8228 treatment partly reversed these detrimental changes. Myocyte cross-sectional area, a measure of @entity1184 , was decreased by 30% in the @entity8228 versus vehicle group, but there was no effect on @entity24397 mRNA. The interstitial collagen fraction increased from 5.4 +/- 0.4% in sham hearts to 10.4 +/- 0.9% in @entity583 hearts and was decreased to 7.9 +/- 0.6% in @entity8228 -treated hearts. A second @entity10178 inhibitor, @entity13586 ( @entity13586 ), also decreased myocyte cross-sectional area and interstitial collagen fraction. TGF-beta, a key regulator of collagen synthesis, was increased in @entity583 hearts. @entity8228 treatment reduced TGF-beta immunostaining by 40%. @entity8228 treatment had no effect on @entity1188 size. These results suggest that @entity10178 products contribute to @entity299 after @entity583 . Thus selected inhibition of @entity10178 may be a therapeutic target for reducing @entity16 after @entity583 .
