Cardiomyocyte VCPIP1 exacerbates doxorubicin-induced cardiotoxicity by stabilizing TFR1

Doxorubicin (DOX) is an effective anthracycline chemotherapeutic agent; however, its clinical application is severely limited by dose-dependent cardiotoxicity. To date, there are no effective preventive or therapeutic strategies for DOX-induced cardiotoxicity (DIC). Deubiquitinases play critical roles in maintaining substrate protein stability and are essential regulators of cardiac homeostasis and injury. In this study, we investigated the role and underlying mechanisms of the cardiomyocyte-derived deubiquitinase valosin-containing protein-interacting protein 1 (VCPIP1) in DIC. We found that VCPIP1 expression was markedly upregulated in the myocardium of DIC mice and was predominantly localized in cardiomyocytes.