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The histone 3 lysine 9 methyltransferase inhibitor chaetocin improves prognosis in a rat model of high salt diet-induced heart failure.
Ono, Tomohiko; Kamimura, Naomi; Matsuhashi, Tomohiro; Nagai, Toshihiro; Nishiyama, Takahiko; Endo, Jin; Hishiki, Takako; Nakanishi, Tsuyoshi; Shimizu, Noriaki; Tanaka, Hirotoshi; Ohta, Shigeo; Suematsu, Makoto; Ieda, Masaki; Sano, Motoaki; Fukuda, Keiichi; Kaneda, Ruri.
Afiliação
  • Ono T; Department of Cardiology, Keio University School of Medicine, Shinjuku-ku Tokyo, Japan.
  • Kamimura N; Department of Biochemistry and Cell Biology, Institute of Development and Aging Sciences, Graduate School of Medicine, Nippon Medical School, Kawasaki, Kanagawa, Japan.
  • Matsuhashi T; Department of Cardiology, Keio University School of Medicine, Shinjuku-ku Tokyo, Japan.
  • Nagai T; Electron Microscope Laboratory, Keio University Hospital, Shinjuku-ku, Tokyo, Japan.
  • Nishiyama T; Department of Cardiology, Keio University School of Medicine, Shinjuku-ku Tokyo, Japan.
  • Endo J; Department of Cardiology, Keio University School of Medicine, Shinjuku-ku Tokyo, Japan.
  • Hishiki T; Department of Biochemistry, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
  • Nakanishi T; Clinical and Translational Research Center, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
  • Shimizu N; Department of Biochemistry, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
  • Tanaka H; MS Business Unit, Shimadzu Corporation, Kyoto, Japan.
  • Ohta S; Division of Rheumatology, Center for Antibody and Vaccine Therapy, IMSUT Hospital, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan.
  • Suematsu M; Division of Rheumatology, Center for Antibody and Vaccine Therapy, IMSUT Hospital, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan.
  • Ieda M; Department of Biochemistry and Cell Biology, Institute of Development and Aging Sciences, Graduate School of Medicine, Nippon Medical School, Kawasaki, Kanagawa, Japan.
  • Sano M; Department of Biochemistry, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
  • Fukuda K; Department of Cardiology, Keio University School of Medicine, Shinjuku-ku Tokyo, Japan.
  • Kaneda R; Department of Cardiology, Keio University School of Medicine, Shinjuku-ku Tokyo, Japan.
Sci Rep ; 7: 39752, 2017 01 04.
Article em En | MEDLINE | ID: mdl-28051130
ABSTRACT
Histone acetylation has been linked to cardiac hypertrophy and heart failure. However, the pathological implications of changes in histone methylation and the effects of interventions with histone methyltransferase inhibitors for heart failure have not been fully clarified. Here, we focused on H3K9me3 status in the heart and investigated the effects of the histone H3K9 methyltransferase inhibitor chaetocin on prognoses in Dahl salt-sensitive rats, an animal model of chronic heart failure. Chaetocin prolonged survival and restored mitochondrial dysfunction. ChIP-seq analysis demonstrated that chronic stress to the heart induced H3K9me3 elevation in thousands of repetitive elements, including intronic regions of mitochondria-related genes, such as the gene encoding peroxisome proliferator-activated receptor-gamma coactivator 1 alpha. Furthermore, chaetocin reversed this effect on these repetitive loci. These data suggested that excessive heterochromatinization of repetitive elements of mitochondrial genes in the failing heart may lead to the silencing of genes and impair heart function. Thus, chaetocin may be a potential therapeutic agent for chronic heart failure.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Cardiomegalia / Insuficiência Cardíaca Tipo de estudo: Prognostic_studies Limite: Animals / Humans / Male Idioma: En Ano de publicação: 2017 Tipo de documento: Article
Texto completo
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PubMed Links
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Cardiomegalia / Insuficiência Cardíaca Tipo de estudo: Prognostic_studies Limite: Animals / Humans / Male Idioma: En Ano de publicação: 2017 Tipo de documento: Article