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Endothelial-to-Mesenchymal Transition: Potential Target of Doxorubicin-Induced Cardiotoxicity

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Abstract

The use of chemotherapeutic agents is becoming more frequent as the proportion of new oncology patients increases worldwide, with prolonged survival after treatment. As one of the most popular chemotherapy drugs, doxorubicin plays a substantial role in the treatment of tumors. Unfortunately, the use of doxorubicin is associated with several adverse effects, particularly severe cardiotoxicity that can be life-threatening, which greatly limits its clinical use. For decades, scientists have tried to explore many cardioprotective agents and therapeutic approaches, but their efficacy remains controversial, and some drugs have even brought about significant adverse effects. The concrete molecular mechanism of doxorubicin-induced cardiotoxicity is still to be unraveled, yet endothelial damage is gradually being identified as an important mechanism triggering the development and progression of doxorubicin-induced cardiotoxicity. Endothelial-to-mesenchymal transition (EndMT), a fundamental process regulating morphogenesis in multicellular organisms, is recognized to be associated with endothelial damage repair and acts as an important factor in the progression of cardiovascular diseases, tumors, and rheumatic immune diseases. Mounting evidence suggests that endothelial–mesenchymal transition may play a non-negligible role in doxorubicin-induced cardiotoxicity. In this paper, we reviewed the molecular mechanisms and signaling pathways of EndMT and outlined the molecular mechanisms of doxorubicin-induced cardiotoxicity and the current therapeutic advances. Furthermore, we summarized the basic principles of doxorubicin-induced endothelial–mesenchymal transition that lead to endothelial dysfunction and cardiotoxicity, aiming to provide suggestions or new ideas for the prevention and treatment of doxorubicin-induced endothelial and cardiac injury.

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  1. Department of Cardiology, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, China

    Jie Feng & Yanqing Wu

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This work was supported by the Beijing Health Promotion Association (20181BCB24013) and Special Funds for Guiding Local Scientific and Technological Development from the Central Government of China (S2019CXSFG0016).

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Jie Feng and Yanqing Wu have no relevant financial or non-financial interests to disclose.

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JF was responsible for the literature search, data compilation, and writing of the paper. YW provided guidance on the design of the article, quality control and review of the article, and was responsible for the overall responsibility, supervision and management of the manuscript.

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Feng, J., Wu, Y. Endothelial-to-Mesenchymal Transition: Potential Target of Doxorubicin-Induced Cardiotoxicity. Am J Cardiovasc Drugs 23, 231–246 (2023). https://doi.org/10.1007/s40256-023-00573-w

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