NF-κB pathway activation during endothelial-to-mesenchymal transition in a rat model of doxorubicin-induced cardiotoxicity.
Biomed Pharmacother
; 130: 110525, 2020 Oct.
Article
em En
| MEDLINE
| ID: mdl-32702633
ABSTRACT
Doxorubicin is a commonly used anthracycline chemotherapeutic agent; however, its application is limited owing to its cardiotoxicity. Current clinical treatments cannot efficiently or fully prevent doxorubicin-induced toxicity, primarily because its pathogenesis and mechanisms of action remain unknown. In this study, we established a rat model of chronic doxorubicin-induced cardiotoxicity, in which the severity of cardiac fibrosis and hydroxyproline levels increased in a time-dependent manner. Doxorubicin damaged the mitochondria and blood vessels and induced autophagy. Cells undergoing endothelial-to-mesenchymal transition (EndoMT)and those expressing endothelial cell and myofibroblast markers were simultaneously observed in vitro and in rats treated with doxorubicin. The NF-κB pathway was activated during EndoMT, andp65 and p-p65 were strongly expressed in the nucleus of endothelial cells in vitro. Taken together, these results suggest that vascular injury and cardiac fibrosis are characteristic symptoms of doxorubicin-induced cardiotoxicity. The NF-κB pathway-associated EndoMT may influence the pathogenesis of doxorubicin-induced cardiotoxicity, and the constituents of this pathway may be potential therapeutic targets to prevent the development of this condition.
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Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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Doxorrubicina
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NF-kappa B
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Células Endoteliais
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Cardiotoxicidade
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Antibióticos Antineoplásicos
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article