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The complement C3-complement factor D-C3a receptor signalling axis regulates cardiac remodelling in right ventricular failure.
Ito, Shogo; Hashimoto, Hisayuki; Yamakawa, Hiroyuki; Kusumoto, Dai; Akiba, Yohei; Nakamura, Takahiro; Momoi, Mizuki; Komuro, Jin; Katsuki, Toshiomi; Kimura, Mai; Kishino, Yoshikazu; Kashimura, Shin; Kunitomi, Akira; Lachmann, Mark; Shimojima, Masaya; Yozu, Gakuto; Motoda, Chikaaki; Seki, Tomohisa; Yamamoto, Tsunehisa; Shinya, Yoshiki; Hiraide, Takahiro; Kataoka, Masaharu; Kawakami, Takashi; Suzuki, Kunimichi; Ito, Kei; Yada, Hirotaka; Abe, Manabu; Osaka, Mizuko; Tsuru, Hiromi; Yoshida, Masayuki; Sakimura, Kenji; Fukumoto, Yoshihiro; Yuzaki, Michisuke; Fukuda, Keiichi; Yuasa, Shinsuke.
Afiliación
  • Ito S; Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
  • Hashimoto H; Division of Cardio-Vascular Medicine, Department of Internal Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka, 830-0011, Japan.
  • Yamakawa H; Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
  • Kusumoto D; Center for Preventive Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
  • Akiba Y; Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
  • Nakamura T; Center for Preventive Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
  • Momoi M; Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
  • Komuro J; Center for Preventive Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
  • Katsuki T; Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
  • Kimura M; Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
  • Kishino Y; Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
  • Kashimura S; Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
  • Kunitomi A; Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
  • Lachmann M; Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
  • Shimojima M; Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
  • Yozu G; Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
  • Motoda C; Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
  • Seki T; Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
  • Yamamoto T; Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
  • Shinya Y; Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
  • Hiraide T; Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
  • Kataoka M; Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
  • Kawakami T; Department of Healthcare Information Management, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
  • Suzuki K; Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
  • Ito K; Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
  • Yada H; Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
  • Abe M; Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
  • Osaka M; Second Department of Internal Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, Fukuoka, 807-8555, Japan.
  • Tsuru H; Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
  • Yoshida M; Department of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
  • Sakimura K; Department of Cardiology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan.
  • Fukumoto Y; Department of Cardiology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan.
  • Yuzaki M; Department of Cardiology, International University of Health and Welfare, Mita Hospital, 1-4-3 Mita Minatoku, Tokyo, 108-8329, Japan.
  • Fukuda K; Department of Animal Model Development, Brain Research Institute, Niigata University, 1-757 Asahimachi-Dori, Chuo-ku, Niigata, 951-8585, Japan.
  • Yuasa S; Department of Life Sciences and Bioethics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
Nat Commun ; 13(1): 5409, 2022 09 15.
Article en En | MEDLINE | ID: mdl-36109509
ABSTRACT
Failure of the right ventricle plays a critical role in any type of heart failure. However, the mechanism remains unclear, and there is no specific therapy. Here, we show that the right ventricle predominantly expresses alternative complement pathway-related genes, including Cfd and C3aR1. Complement 3 (C3)-knockout attenuates right ventricular dysfunction and fibrosis in a mouse model of right ventricular failure. C3a is produced from C3 by the C3 convertase complex, which includes the essential component complement factor D (Cfd). Cfd-knockout mice also show attenuation of right ventricular failure. Moreover, the plasma concentration of CFD correlates with the severity of right ventricular failure in patients with chronic right ventricular failure. A C3a receptor (C3aR) antagonist dramatically improves right ventricular dysfunction in mice. In summary, we demonstrate the crucial role of the C3-Cfd-C3aR axis in right ventricular failure and highlight potential therapeutic targets for right ventricular failure.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Disfunción Ventricular Derecha / Insuficiencia Cardíaca Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2022 Tipo del documento: Article País de afiliación: Japón
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Disfunción Ventricular Derecha / Insuficiencia Cardíaca Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2022 Tipo del documento: Article País de afiliación: Japón