Disruption of COX-2 modulates gene expression and the cardiac injury response to doxorubicin

American Journal of Physiology. Heart and Circulatory Physiology
Tomas G NeilanDesmond J Fitzgerald

Abstract

To determine the role of cyclooxygenase (COX)-2 in anthracycline-induced cardiac toxicity, we administered doxorubicin (Dox) to mice with genetic disruption of COX-2 (COX-2-/-). After treatment with Dox, COX-2-/- mice had increased cardiac dysfunction and cardiac cell apoptosis compared with Dox-treated wild-type mice. The expression of the death-associated protein kinase-related apoptosis-inducing protein kinase-2 was also increased in Dox-treated COX-2-/- animals. The altered gene expression, cardiac injury, and dysfunction after Dox treatment in COX-2-/- mice was attenuated by a stable prostacyclin analog, iloprost. Wild-type mice treated with Dox developed cardiac fibrosis that was absent in COX-2-/- mice and unaffected by iloprost. These results suggest that genetic disruption of COX-2 increases the cardiac dysfunction after treatment with Dox by an increase in cardiac cell apoptosis. This Dox-induced cardiotoxicity in COX-2-/- mice was attenuated by a prostacyclin analog, suggesting a protective role for prostaglandins in this setting.

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Citations

Jul 20, 2011·Cardiovascular Toxicology·Maria Antonietta PanaroAngela Tesse
Jun 24, 2008·Cardiovascular Research·Miguel A FriasUrsula Lang
Dec 9, 2008·American Journal of Physiology. Heart and Circulatory Physiology·Aaron P KelloggRodica Pop-Busui
Sep 29, 2011·The Journal of Surgical Research·Michael ScullyAnthony J Cunningham
Jul 25, 2009·The Journal of Surgical Research·Gang ChenDavid J Bouchier-Hayes
Sep 1, 2015·The Journal of Surgical Research·Zenggeng WangChunli Yang
Jan 9, 2009·Journal of Cardiovascular Pharmacology and Therapeutics·David S HydockReid Hayward
Jul 30, 2009·British Journal of Cancer·G A DohertyD J Fitzgerald
Apr 15, 2008·Medicine and Science in Sports and Exercise·David S HydockReid Hayward

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