HMGB1 contributes to adriamycin-induced cardiotoxicity via up-regulating autophagy

作者：Luo, Peihua; Zhu, Yi; Chen, Min; Yan, Hao; Yang, Bo; Yang, Xiaochun^*; He, Qiaojun^*

来源：Toxicology Letters, 2018, 292: 115-122.

DOI：10.1016/j.toxlet.2018.04.034

• Adriamycin
• Cardiotoxicity
• Autophagy
• HMGB1
• YAP

Adriamycin (ADR) is one of the most widely used and effective anthracycline antitumor agents in the treatment of certain hematological malignancies and solid tumors. However, the severe cardiotoxicity of ADR limits its clinical application. So far, the mechanism of the cardiotoxicity of ADR has not been completely clarified. In our research, cardiomyocyte autophagy and cardiac damage were observed in accompany ADR treatment, and autophagy appeared earlier than cardiac damage. Inhibition of autophagy by silencing ATG7 improved the survival rate of cardiomyocytes treated with ADR. The release of HMGB1 increased after ADR treatment, and silencing HMGB1 could reverse cardiomyocyte damage by attenuating autophagy. In addition, the expression of YAP was decreased, and overexpressing YAP down-regulated HMGB1 and alleviated cardiomyocyte damage. These results indicated that autophagy was the leading cause of ADR-induced cardiotoxicity, and HMGB1 played a vital role in the process of up-regulating autophagy.

• 出版日期2018-8
• 单位浙江医院; 浙江大学