| First Author | Neilan TG | Year | 2006 |
| Journal | Am J Physiol Heart Circ Physiol | Volume | 291 |
| Issue | 2 | Pages | H532-6 |
| PubMed ID | 16617129 | Mgi Jnum | J:116411 |
| Mgi Id | MGI:3694275 | Doi | 10.1152/ajpheart.00863.2005 |
| Citation | Neilan TG, et al. (2006) Disruption of COX-2 modulates gene expression and the cardiac injury response to doxorubicin. Am J Physiol Heart Circ Physiol 291(2):H532-6 |
| abstractText | 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. |
