Atorvastatin Ameliorates Doxorubicin-Induced Cardiomyopathy by Regulating the Autophagy-Lysosome Pathway and Its Upstream Regulatory Factor Transcription Factor EB.

ABSTRACT

ABSTRACT Doxorubicin is a widely used anticancer drug in clinical practice, and its myocardial toxicity is the main concern in oncotherapy. Statins are commonly used as hypolipidemic drugs. Recent studies have also focused on the effects of statins on autophagy. Autophagy is a process in which cells consume their own cytoplasm or organelles after stimulation and finally degrade the phagosome in the lysosome. Transcription factor EB (TFEB) is the main factor regulating lysosomal gene transcription and function. We found that atorvastatin (ATO) increased TFEB protein levels and the ratio of lysosomal-associated membrane protein 2/LC3B in the myocardial tissue of mice with doxorubicin-induced cardiomyopathy (DIC). Therefore, we speculated that ATO may improve cardiac function in mice with DIC by increasing the expression of TFEB to enhance lysosomal function and autophagy. This study explored the role of TFEB in DIC and the possible mechanism of ATO in improving DIC and used statins to prevent and treat DIC; various dilated cardiomyopathy and heart failure diseases provide more experimental evidence. All relevant data are within the article and its supporting information files.