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

Tomas G. Neilan, Glen A. Doherty, Gang Chen, Catherine Deflandre, Hester McAllister, Ryan K. Butler, Sarah E. McClelland, Elaine Kay, Leslie R. Ballou, Desmond J. Fitzgerald

Research output: Contribution to journalArticle

20 Scopus citations

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 apoptosisinducing 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.

Original languageEnglish (US)
Pages (from-to)H532-H536
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume291
Issue number2
DOIs
StatePublished - Aug 10 2006
Externally publishedYes

Keywords

  • Apoptosis
  • Cyclooxygenase

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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    Neilan, T. G., Doherty, G. A., Chen, G., Deflandre, C., McAllister, H., Butler, R. K., McClelland, S. E., Kay, E., Ballou, L. R., & Fitzgerald, D. J. (2006). Disruption of COX-2 modulates gene expression and the cardiac injury response to doxorubicin. American Journal of Physiology - Heart and Circulatory Physiology, 291(2), H532-H536. https://doi.org/10.1152/ajpheart.00863.2005