Статья

NF-κB pathway activation during endothelial-to-mesenchymal transition in a rat model of doxorubicin-induced cardiotoxicity

Anji XuDepartment of Head and Neck Surgery, Central Laboratory, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan Province, China. Electronic address: [email protected]Fei‐Yan DengCollege of Medical Imaging, Changsha Medical University, China. Electronic address: [email protected]Yongyi ChenNursing Department, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Changsha, Hunan Province, China. Electronic address: [email protected]Yu KongInstitute of Neuroscience, Chinese Academy of Science, Shanghai, China. Electronic address: [email protected]Lijun PanInstitute of Neuroscience, Chinese Academy of Science, Shanghai, China. Electronic address: [email protected]Qianjin LiaoDepartment of Head and Neck Surgery, Central Laboratory, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan Province, China. Electronic address: [email protected]Rao ZhenDepartment of Head and Neck Surgery, The First People's Hospital of Changde City, Changde, Hunan Province, China. Electronic address: [email protected]Luyuan XieDepartment of Head and Neck Surgery, Central Laboratory, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan Province, China. Electronic address: [email protected]Chao‐Ling YaoDepartment of Head and Neck Surgery, Central Laboratory, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan Province, China. Electronic address: [email protected]Sha LiDepartment of Head and Neck Surgery, Central Laboratory, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan Province, China. Electronic address: [email protected]Xiaoling ZengDepartment of Head and Neck Surgery, Central Laboratory, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan Province, China. Electronic address: [email protected]Xiaomei ZhuNursing Department, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Changsha, Hunan Province, China. Electronic address: [email protected]Huayun LiuNursing Department, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Changsha, Hunan Province, China. Electronic address: [email protected]Nina J. GaoPathology Department, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Changsha, Hunan Province, China. Electronic address: [email protected]Lei XuePathology Department, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Changsha, Hunan Province, China. Electronic address: [email protected]Fen ChenDepartment of Cardiology, Union Hospital, Tongji Medial College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China. Electronic address: [email protected]Guoxing XuDepartment of Respiratory and Critical Care Medicine, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: [email protected]Di WeiNursing Department, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Changsha, Hunan Province, China. Electronic address: [email protected]Xiao ZhouDepartment of Head and Neck Surgery, Central Laboratory, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan Province, China. Electronic address: [email protected]Zan LiDepartment of Head and Neck Surgery, Central Laboratory, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan Province, China. Electronic address: [email protected]Xiaowu Sheng

2020en

ABI

Аннотация

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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Идентификаторы

DOI: 10.1016/j.biopha.2020.110525

Цитирования и источники

Цитирований: 2Использованных источников: 0

Показатели — AkademScholar