1. Exercise preconditioning inhibits doxorubicin-induced cardiotoxicity via YAP/STAT3 signaling
- Author
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Chuan-Zhi Wang, Heng-Zhi Guo, Jing-Zhi Leng, Zhi-De Liang, Jing-Tai Wang, Li-Jie Luo, Shi-Qiang Wang, and Yang Yuan
- Subjects
Exercise preconditioning ,Doxorubicin ,Cardiotoxicity ,YAP ,STAT3 ,Cardiac protection ,Science (General) ,Q1-390 ,Social sciences (General) ,H1-99 - Abstract
Doxorubicin (DOX) possesses strong anti-tumor effects but is limited by its irreversible cardiac toxicity. The relationship between exercise, a known enhancer of cardiovascular health, and DOX-induced cardiotoxicity has been a focus of recent research. Exercise has been suggested to mitigate DOX's cardiac harm by modulating the Yes-associated protein (YAP) and Signal transducer and activator of transcription 3 (STAT3) pathways, which are crucial in regulating cardiac cell functions and responses to damage. This study aimed to assess the protective role of exercise preconditioning against DOX-induced cardiac injury. We used Sprague–Dawley rats, divided into five groups (control, DOX, exercise preconditioning (EP), EP-DOX, and verteporfin + EP + DOX), to investigate the potential mechanisms. Our findings, including echocardiography, histological staining, Western blot, and q-PCR analysis, demonstrated that exercise preconditioning could alleviate DOX-induced cardiac dysfunction and structural damage. Notably, exercise preconditioning enhanced the nuclear localization and co-localization of YAP and STAT3. Our study suggests that exercise preconditioning may counteract DOX-induced cardiotoxicity by activating the YAP/STAT3 pathway, highlighting a potential therapeutic approach for reducing DOX's cardiac side effects.
- Published
- 2024
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