Vericiguat attenuates doxorubicin-induced cardiotoxicity through the PRKG1/PINK1/STING axis.
Transl Res
; 273: 90-103, 2024 Nov.
Article
em 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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Quinases
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Doxorrubicina
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Miócitos Cardíacos
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Cardiotoxicidade
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Proteínas de Membrana
Limite:
Animals
Idioma:
En
Revista:
Transl Res
/
Transl. res
/
Translational research
Assunto da revista:
MEDICINA
/
TECNICAS E PROCEDIMENTOS DE LABORATORIO
Ano de publicação:
2024
Tipo de documento:
Article