Cardiomyocyte cyclooxygenase-2 influences cardiac rhythm and function.
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.
Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, PA 19104, USA.
Dairong
D
Wang
Vickas V
VV
Patel
Emanuela
E
Ricciotti
Rong
R
Zhou
Mark D
MD
Levin
Ehre
E
Gao
Zhou
Z
Yu
Victor A
VA
Ferrari
Min Min
MM
Lu
Junwang
J
Xu
Hualei
H
Zhang
Yiqun
Y
Hui
Yan
Y
Cheng
Nataliya
N
Petrenko
Ying
Y
Yu
Garret A
GA
FitzGerald
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000502:physiology*; D017353:Gene Deletion; D006339:Heart Rate / Q000235:genetics; D006984:Hypertrophy / Q000139:chemically induced / Q000201:enzymology; D051379:Mice; D018345:Mice, Knockout; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000201:enzymology / Q000473:pathology* / Q000502:physiology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2