[en] 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.
Research center :
Department of Clinical Pharmacology, Royal College of Surgeons in Ireland Department of Surgery and Pathology, Beaumont Hospital, Ireland Department of Veterinary Medicine, University College Dublin, Ireland Department of Veterans Affairs Medical Center, Departments of Medicine and Molecular Sciences, University of Tennessee, Memphis, Tennessee
Disciplines :
Oncology Cardiovascular & respiratory systems
Author, co-author :
Neilan, Tomas
Doherty, Glen
Chen, Gang
Deflandre, Catherine ; Université de Liège - ULiège > 3e an. bac. lang. & litt. mod., or. germ.
McAllister, Hester
Butler, Ryan
McClelland, Sarah
Kay, Elaine
Ballou, Leslie
Fitzgerald
Language :
English
Title :
Disruption of COX-2 modulates gene expression and the cardiac injury response to doxorubicin
Publication date :
2006
Journal title :
American Journal of Physiology - Heart and Circulatory Physiology
ISSN :
0363-6135
eISSN :
1522-1539
Publisher :
American Physiological Society, Bethesda, United States - Maryland
Volume :
291
Issue :
2
Pages :
H532-H536
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
Irish Health Research Board Health Research Board and by the Higher Education Authority of Ireland Programme for Research in Third Level Institutions
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