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

Royal College of Surgeons in Ireland, Dublin, Leinster, Ireland
AJP Heart and Circulatory Physiology (Impact Factor: 3.84). 09/2006; 291(2):H532-6. DOI: 10.1152/ajpheart.00863.2005
Source: PubMed


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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    • "The classification of chemotherapy drugs, cardiac side-effects, underlying mechanisms, associated risk factors, as well as the management of cancer chemotherapy are summarized by Jean-Jacques Monsuez, [28], as indicated in the paper, cancer chemotherapy induces cardiomyocyte damage through oxidative stress (ROS production ). Several studies suggest iloprost protects against DOXinduced cardiomyocyte injury in vitro and in vivo without compromising tumor suppression [30] [31] [32]. "
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