Cardiomyocyte cyclooxygenase-2 influences cardiac rhythm and function.

Abstract:

:Nonsteroidal anti-inflammatory drugs selective for inhibition of COX-2 increase heart failure and elevate blood pressure. The COX-2 gene was floxed and crossed into merCremer mice under the alpha-myosin heavy-chain promoter. Tamoxifen induced selective deletion of COX-2 in cardiomyocytes depressed cardiac output, and resulted in weight loss, diminished exercise tolerance, and enhanced susceptibility to induced arrhythmogenesis. The cardiac dysfunction subsequent to pressure overload recovered progressively in the knockouts coincident with increasing cardiomyocyte hypertrophy and interstitial and perivascular fibrosis. Inhibition of COX-2 in cardiomyocytes may contribute to heart failure in patients receiving nonsteroidal anti-inflammatory drugs specific for inhibition of COX-2.

authors

Wang D,Patel VV,Ricciotti E,Zhou R,Levin MD,Gao E,Yu Z,Ferrari VA,Lu MM,Xu J,Zhang H,Hui Y,Cheng Y,Petrenko N,Yu Y,FitzGerald GA

doi

10.1073/pnas.0805806106

subject

Has Abstract

pub_date

2009-05-05 00:00:00

pages

7548-52

issue

18

eissn

0027-8424

issn

1091-6490

pii

0805806106

journal_volume

106

pub_type

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