Identification of the molecular basis of doxorubicin-induced cardiotoxicity
Menée à l'aide d'un modèle murin, cette étude met en évidence un mécanisme impliquant la topoisomérase II-bêta dans la toxicité cardiovasculaire associée à la doxorubicine
Doxorubicin is believed to cause dose-dependent cardiotoxicity through redox cycling and the generation of reactive oxygen species (ROS). Here we show that cardiomyocyte-specific deletion of Top2b (encoding topoisomerase-II
β) protects cardiomyocytes from doxorubicin-induced DNA double-strand breaks and transcriptome changes that are responsible for defective mitochondrial biogenesis and ROS formation. Furthermore, cardiomyocyte-specific deletion of Top2b protects mice from the development of doxorubicin-induced progressive heart failure, suggesting that doxorubicin-induced cardiotoxicity is mediated by topoisomerase-IIβ in cardiomyocytes.
Nature Medicine 2012