NF-?B pathway activation during endothelial-to-mesenchymal transition in a rat model of doxorubicin-induced cardiotoxicity - 27/10/20
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Graphical abstract |
Highlights |
• | Doxorubicin-induced cardiotoxicity leads to cardiac fibrosis. |
• | Cells undergo endothelial-to-mesenchymal transition in doxorubicin treated rats. |
• | NF-κB pathway related EndoMT may influence doxorubicin-induced cardiotoxicity. |
• | NF-κB pathway may be a therapeutic target for doxorubicin-induced cardiotoxicity. |
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.
El texto completo de este artículo está disponible en PDF.Abbreviations : EndoMT, ECM, ECs, PECAM-1/CD31, vWF, α-SMA, FSP-1, NF-κB
Keywords : Doxorubicin, Cardiotoxicity, Endothelial-to-mesenchymal transition, Myofibroblast, NF-κB pathway, Cardiac fibrosis
Esquema
Vol 130
Artículo 110525- octobre 2020 Regresar al númeroBienvenido a EM-consulte, la referencia de los profesionales de la salud.
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