Key result
ATF4 alleviates doxorubicin-induced cardiomyopathy by boosting H2S production and antioxidant defenses in mice.
Why the study?
Doxorubicin-induced cardiotoxicity limits its clinical use due to dose-dependent ROS generation, and the role of ATF4 in this cardiomyopathy is unclear.
Does ATF4 modify doxorubicin-induced cardiomyopathy in mouse models?
Does ATF4 modify doxorubicin-induced cardiomyopathy in mouse models?
ATF4 protects against doxorubicin-induced cardiomyopathy by promoting H2S production and antioxidant defense, identifying it as a potential therapeutic target.
ATF4 modulation should not yet inform doxorubicin cardiotoxicity management; leaves open its H2S-antioxidant axis as a preclinical research target.
Doxorubicin (DOX) remains a cornerstone in cancer treatment. However, its clinical utilization is significantly hampered by dose-dependent cardiotoxicity. The generation of reactive oxygen species (ROS) constitutes the central component of the pathogenesis of DOX-induced cardiotoxicity. Activating transcription factor 4 (ATF4) has been demonstrated to exert a cardioprotective effect and augment cardiac antioxidative capacity in settings of heart failure. To explore the role of ATF4 in DOX-induced cardiomyopathy, cardiac-specific ATF4 conditional heterozygous mice and AAV9 mediated ATF4 overexpression mouse models were utilized. Cardiac function was assessed by echocardiography. The upstream regulator and downstream mediator of ATF4 were evaluated using RNA-seq analysis and further verified using ChIP assay and luciferase reporter assay. ATF4
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Xu et al. (2026) studied Doxorubicin-induced cardiomyopathy. ATF4 conditional heterozygosity and AAV9 mediated ATF4 overexpression was evaluated on Cardiac function (assessed by echocardiography) and molecular pathways. ATF4 alleviates doxorubicin-induced cardiomyopathy by promoting H2S production and antioxidant defense in mouse models.
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