Endothelial Transcription Factor EB Protects Against Doxorubicin-Induced Endothelial Toxicity and Cardiac Dysfunction

BACKGROUND: Doxorubicin (DOX), an effective chemotherapeutic drug for various cancers, has been demonstrated to induce cardiovascular toxicity in cancer survivors. Endothelial cell (EC) dysfunction is recognized to play a critical role in the onset and severity of cardiotoxicity associated with DOX. TFEB (transcription factor EB), a master regulator of autophagy and lysosome biogenesis, regulates cardiovascular homeostasis. In the present study, we aimed to test whether endothelial TFEB protects against EC damage and alleviates cardiac dysfunction induced by DOX treatment. METHODS: gene (Disabled homolog 2) were subjected to measurement of cardiac function and fibrosarcoma growth under DOX treatment. RESULTS: deficiency abolished the protective effect of EC TFEB on DOX-induced cardiac dysfunction. CONCLUSIONS: Taken together, endothelial TFEB protects against EC damage and cardiac dysfunction, constituting a potential target for treating cardiotoxicity induced by DOX. Our study provides new mechanistic insights into cardiotoxicity associated with chemotherapy.