Doxorubicin-Induced Cardiotoxicity Animal Model

Permission was granted for all the animal experiments with local animal authorities at Hannover Medical School and Niedersachsen Landesamt für Verbraucherschutz (TVA 14/1665). A previously described mouse model of doxorubicin-induced cardiotoxicity was used.4 Adult C57BL/6N male mice were given doxorubicin at a dose of 5 mg/kg weekly for 5 consecutive weeks to establish doxorubicin-induced cardiotoxicity. 2 × 10¹² viral particles of AAV9-control or AAV9-miR-212/132 were administered a day before starting the doxorubicin treatment. Control mice received AAV9-control virus together with saline injections. One week after the last doxorubicin injection (total, 5 weeks), echocardiographic data were acquired to assess the cardiac function, and animals were sacrificed. Echocardiography data were recorded using the Vevo 2100 system (FUJIFILM VisualSonics), and analysis was performed with standard imaging protocols (M-mode and B-mode) using Vevostrain software (FUJIFILM VisualSonics). All the animal experiments were randomized and blinded.