• Xianghui Zeng, Hao Zhang, Tianyu Xu, Xiyuan Mei, Xiao Wang, Qiling Yang, Zhen Luo, Qingchun Zeng, Dingli Xu, and Hao Ren.
• State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, China; Key Laboratory For Organ Failure Research, Ministry of Education of the People's Republic of China, Guangzhou, China; Department of Cardiology, Ganzhou Hospital of Traditional Chinese Medicine, Ganzhou, Jiangxi, China.
• Transl Res. 2024 Nov 1; 273: 9010390-103.

AbstractDoxorubicin (DOX) is restricted due to its severe cardiotoxicity. There is still a lack of viable and effective drugs to prevent or treat DOX-induced cardiotoxicity(DIC). Vericiguat is widely used to treat heart failure with reduced ejection fraction. However, it is not clear whether vericiguat can improve DIC. In the present study, we constructed a DIC model using mice and neonatal rat cardiomyocytes and found that vericiguat ameliorated DOX-induced cardiac insufficiency in mice, restored DOX-induced mitochondrial dysfunction in neonatal rat cardiomyocytes, and inhibited the expression of inflammatory factors. Further studies showed that vericiguat improved mitochondrial dysfunction and reduced mtDNA leakage into the cytoplasm by up-regulating PRKG1, which activated PINK1 and then inhibited the STING/IRF3 pathway to alleviate DIC. These findings demonstrate for the first time that vericiguat has therapeutic potential for the treatment of DIC.Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.

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