Impacts of Dysfunction in Cardiac Macrophage on Heart Disease

• Project/Area Number: 17K19644
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Research Field: General internal medicine and related fields
• Research Institution: The University of Tokyo
• Principal Investigator: Fujiu Katsuhito 東京大学, 医学部附属病院, 特任准教授 (30422306)
• Project Period (FY): 2017-06-30 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000); Fiscal Year 2018: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000); Fiscal Year 2017: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
• Keywords: 心不全 / 心臓マクロファージ / マクロファージ / 臓器連関 / 老化

Outline of Final Research Achievements

Since the effect of cardiac macrophage dysfunction on cardiac function has not been known so far, this study was conducted. When stress on the heart occurs, cardiac macrophages sense the stress via receptor T, and as a result, secrete proteins A, B, C, and D, and protect the heart.
Macrophage specific receptor T knockout mice had impaired cardiac function and were more likely to be impaired by cardiac stress. This receptor T is also decreased in cardiac macrophages of human heart failure, and it is possible that this system is involved in the development of heart failure in humans.

Academic Significance and Societal Importance of the Research Achievements

心不全は、再発を繰り返し、医療費の増加を引き起こしている疾患であり、その解決が必要である。心臓の研究は心筋細胞に着目した研究が多く、これまでの薬剤は心筋細胞が標的なものが多かった。今回心臓内に存在している心筋細胞以外の細胞に着目して、創薬に資する研究を行った。その結果新しい治療標的を発見することが出来た。今後、新しい治療標的に対する治療法の開発に役立つものと思われる。
結果、健康寿命の延長や医療費の軽減に役立つことが期待できる。

Research Products

• [Journal Article] Response to Comment on “Ghost cytometry” (2019)
  • Author(s): Sadao Ota, Ryoichi Horisaki, Yoko Kawamura, Masashi Ugawa, Issei Sato, Hiroaki Adachi, Satoko Yamaguchi, Katsuhito Fujiu, Kayo Waki, Hiroyuki Noji
  • Journal Title: Science Volume: 364 Issue: 6437
  • DOI: 10.1126/science.aav3136
  • Peer Reviewed
• [Journal Article] Can Anti-inflammatory Therapy Prevent Atrial Fibrillation in Myocardial Infarction Patients? (2018)
  • Author(s): Nakayama Y, Fujiu K
  • Journal Title: International Heart Journal Volume: 59 Issue: 1 Pages: 3-5
  • DOI: 10.1536/ihj.17-662
  • NAID: 130006321432
  • ISSN: 1349-2365, 1349-3299
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A heart-brain-kidney network controls adaptation to cardiac stress through tissue macrophage activation and cellular communication (2017)
  • Author(s): Fujiu K, Shibata M, Nakayama Y, Ogata F, Matsumoto S, Noshita K, Iwami S, Nakae S, Komuro I, Nagai R, Manabe I
  • Journal Title: Nature Medicine Volume: 印刷中 Issue: 5 Pages: 611-622
  • DOI: 10.1038/nm.4326
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Testing the Feasibility and Usability of a Novel Smartphone-Based Self-Management Support System for Dialysis Patients: A Pilot Study (2017)
  • Author(s): Hayashi Aki、Yamaguchi Satoko、Waki Kayo、Fujiu Katsuhito、Hanafusa Norio、Nishi Takahiro、Tomita Hyoe、Kobayashi Haruka、Fujita Hideo、Kadowaki Takashi、Nangaku Masaomi、Ohe Kazuhiko
  • Journal Title: JMIR Research Protocols Volume: 6 Issue: 4 Pages: e63-e63
  • DOI: 10.2196/resprot.7105
  • Peer Reviewed
• [Journal Article] Cardiac Resynchronization Therapy in Patients with Ebstein's Anomaly (2017)
  • Author(s): Numata G, Amiya E, Kojima T, Fujiu K, Hatano M, Watanabe M, Komuro I
  • Journal Title: International Heart Journal Volume: 58 Issue: 5 Pages: 816-819
  • DOI: 10.1536/ihj.16-580
  • NAID: 130006179198
  • ISSN: 1349-2365, 1349-3299
  • Peer Reviewed
• [Presentation] Renal Collecting Duct Epithelial Cell Controls Kidney Disease and Adaptation to Cardiac Stress through Tissue Macrophage Activation (2018)
  • Author(s): Katsuhito Fujiu
  • Organizer: ISN Frontiers Meetings
  • Int'l Joint Research / Invited
• [Presentation] Cardiac Macrophage is Required to Avoid Heart Failure and Cardiac Sudden Death after Pressure Overload (2017)
  • Author(s): Katsuhito Fujiu
  • Organizer: Keystone Symposia Conference: Mitochondria, Metabolism and Heart
  • Int'l Joint Research / Invited
• [Presentation] Cardiac Macrophage is a Novel Target of Regenerative Medicine on Arrhythmia, Regenerative Medicine and Arrhythmias (2017)
  • Author(s): Katsuhito Fujiu
  • Organizer: The joint meeting of the 10th Asia Pacific Heart Rhythm Society Scientific Session (APHRS 2017) and the 64th Annual Meeting of the Japanese Heart Rhythm Society (JHRS2017)
  • Int'l Joint Research / Invited
• [Presentation] HIS bundle pacing for bradycardia patients (2017)
  • Author(s): Katsuhito Fujiu
  • Organizer: The joint meeting of the 10th Asia Pacific Heart Rhythm Society Scientific Session (APHRS 2017) and the 64th Annual Meeting of the Japanese Heart Rhythm Society (JHRS2017)
  • Int'l Joint Research / Invited