title: Protein Quality Control Dysfunction in Cardiovascular Complications Induced by Anti-Cancer Drugs.
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.
authors.affiliation: Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.|Department of Clinical Research and Development, National Cerebral and Cardiovascular Center, Osaka, Japan.
authors.forename: Hai Ying
authors.initials: HY
authors.lastname: Fu
authors.affiliation: Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan.
authors.forename: Mikio
authors.initials: M
authors.lastname: Mukai
authors.affiliation: Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan.
authors.forename: Nobuhisa
authors.initials: N
authors.lastname: Awata
authors.affiliation: Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Sakata
authors.affiliation: Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan.
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Hori
authors.affiliation: Department of Cardiorenal and Cerebrovascular Medicine, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Mikicho, Kita-gun, Kagawa Prefecture, 761-0793, Japan. minamino@med.kagawa-u.ac.jp.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Minamino
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001343:Autophagy / Q000187:drug effects; D066126:Cardiotoxicity; D002318:Cardiovascular Diseases / Q000139:chemically induced* / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000187:drug effects / Q000378:metabolism; D017510:Protein Folding; D011506:Proteins / Q000378:metabolism*; D059748:Proteolysis; D054875:Ubiquitination
chemical_list: D000970:Antineoplastic Agents; D011506:Proteins; D046988:Proteasome Endopeptidase Complex
keywords: Anti-cancer drugs; Autophagy-lysosome system; Cardiovascular complications; Endoplasmic reticulum; Protein quality control; Ubiquitin-proteasome system