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Vericiguat attenuates doxorubicin-induced cardiotoxicity through the PRKG1/PINK1/STING axis.
Zeng, Xianghui; Zhang, Hao; Xu, Tianyu; Mei, Xiyuan; Wang, Xiao; Yang, Qiling; Luo, Zhen; Zeng, Qingchun; Xu, Dingli; Ren, Hao.
Afiliación
  • Zeng X; 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
  • Zhang H; 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.
  • Xu T; NHC Key Laboratory of Assisted Circulation, Department of Cardiology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China.
  • Mei X; 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.
  • Wang X; 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.
  • Yang Q; 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.
  • Luo Z; 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.
  • Zeng Q; 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.
  • Xu D; 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. Electronic address: dinglixu@smu.edu.cn.
  • Ren H; Key Laboratory For Organ Failure Research, Ministry of Education of the People's Republic of China, Guangzhou, China; Department of Rheumatology, Nanfang Hospital, Southern Medical University, Guangzhou, China. Electronic address: renhao67@aliyun.com.
Transl Res ; 273: 90-103, 2024 Nov.
Article en En | MEDLINE | ID: mdl-39059761
ABSTRACT
Doxorubicin (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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Quinasas / Doxorrubicina / Miocitos Cardíacos / Cardiotoxicidad / Proteínas de la Membrana Límite: Animals Idioma: En Revista: Transl Res Asunto de la revista: MEDICINA / TECNICAS E PROCEDIMENTOS DE LABORATORIO Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Quinasas / Doxorrubicina / Miocitos Cardíacos / Cardiotoxicidad / Proteínas de la Membrana Límite: Animals Idioma: En Revista: Transl Res Asunto de la revista: MEDICINA / TECNICAS E PROCEDIMENTOS DE LABORATORIO Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos