ANTHRACYCLINE INDUCED CARDIOTOXICITY

Another mechanism contributing to anthracycline induced cardiotoxicity is the disruption of

sarcomere maintenance. Anthracycline exposure in animal models leads to the downregulation of
important transcriptional factors necessary for cardiac sarcomere synthesis. GATA4 is a zinc
finger transcriptional factor involved in regulating sarcomere protein expression and in cell
survival signaling. Myocardial GATA4 regulates cardiac-specific and anti-apoptotic genes.
Several GATA4 regulated genes are suppressed by anthracycline exposure. Thus downregulation
of GATA4 by anthracyclines suppresses the ability of cardiac myocytes to synthesize new
protein.