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Protein Quality Control Dysfunction in Cardiovascular Complications Induced by Anti-Cancer Drugs

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Abstract

Cardiovascular complications, including heart failure, hypertension, ischemic syndromes and venous thromboembolism, have been identified in patients treated with anti-cancer drugs. Oxidative stress, mitochondrial dysfunction and DNA synthesis inhibition are considered to be responsible for the cardiotoxicity induced by these agents. Protein quality control (PQC) has 3 major components, including the endoplasmic reticulum (ER), the ubiquitin-proteasome system (UPS) and the autophagy-lysosome system, and participates in protein folding and degradation to maintain protein homeostasis. We have demonstrated that PQC dysfunction is a new causal mechanism for the development of cardiac hypertrophy and failure. Increasing evidence shows that anti-cancer drugs, such as tyrosine kinase inhibitors, proteasome inhibitors, anthracyclines and autophagy inhibitors, cause PQC dysfunction. Here, we provide an overview of the potential role of PQC dysfunction in the development of cardiovascular complications induced by anti-cancer drugs.

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Authors and Affiliations

  1. Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Osaka, Japan

    Hai Ying Fu & Yasushi Sakata

  2. Department of Clinical Research and Development, National Cerebral and Cardiovascular Center, Osaka, Japan

    Hai Ying Fu

  3. Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan

    Mikio Mukai, Nobuhisa Awata & Masatsugu Hori

  4. Department of Cardiorenal and Cerebrovascular Medicine, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Mikicho, Kita-gun, Kagawa Prefecture, 761-0793, Japan

    Tetsuo Minamino

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  1. Hai Ying Fu
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  3. Nobuhisa Awata
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Correspondence to Tetsuo Minamino.

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Conflict of Interest

YS and TM received research grant from Takeda Pharmaceutical Company Limited., Novartis Pharma K. K., Pfizer Japan Inc., Kyowa Hakko Kirin Co., Ltd., and Ono Pharmaceutical CO., Ltd. FH, MM, NA and MH have no disclosures.

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Fu, H.Y., Mukai, M., Awata, N. et al. Protein Quality Control Dysfunction in Cardiovascular Complications Induced by Anti-Cancer Drugs. Cardiovasc Drugs Ther 31, 109–117 (2017). https://doi.org/10.1007/s10557-016-6709-7

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