Impacts of Dysfunction in Cardiac Macrophages on Arrhythmia

• Project/Area Number: 26461125
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• 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): 2014-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 不整脈 / 心不全 / マクロファージ / 炎症 / 免疫細胞 / アンフィレグリン / 心臓 / 突然死 / 細胞間相互作用

Outline of Final Research Achievements

We have studied the novel function of cardiac resident macrophage on cardiac physiological function. First we found the cardiac macrophage is required for its stress response against cardiac pressure overload. In addition, making cardiac rhythm is another cardiac basic role beyond cardiac contraction. Macrophage depleted mouse by clodronate liposome administration resulted in severe arrhythmia and death. These results indicated cardiac macrophages are involved in cardiac rhythm making.

Research Products

• [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
• [Journal Article] Electromagnetic interference between continuous-flow left ventricular assist device and cardiac resynchronization therapy defibrillator due to an unrecognized mechanism. (2015)
  • Author(s): Yokota J, Fujiu K, Tanimito H, Nebiya H, Kashiwa K, Kinoshita O, Nawata K, Kimura M, Satsu T, Chou K, Sumitani M, Ono M, Komuro I.
  • Journal Title: Int J Cardiol Volume: 179 Pages: 510-513
  • DOI: 10.1016/j.ijcard.2014.11.021
  • Peer Reviewed
• [Journal Article] Simultaneous downregulation of KLF5 and Fli1 is a key feature underlying systemic sclerosis (2014)
  • Author(s): Noda, S
  • Journal Title: Nat Commun Volume: 5 Issue: 1 Pages: 5797-5797
  • DOI: 10.1038/ncomms6797
  • Peer Reviewed / Open Access
• [Journal Article] Thoracic Spinal Cord Stimulation for Heart Failure as a Restorative Treatment (SCS HEART study): first-in-man experience. (2014)
  • Author(s): Tse HF1, Turner S2, Sanders P3, Okuyama Y4, Fujiu K5, Cheung CW6, Russo M7, Green MD8, Yiu KH6, Chen P9, Shuto C9, Lau EO9, Siu CW6.
  • Journal Title: Heart Rhythm. Volume: 12 Issue: 3 Pages: 588-595
  • DOI: 10.1016/j.hrthm.2014.12.014
  • Peer Reviewed
• [Journal Article] Phenotypic modulation of smooth muscle cells in lymphoedema. (2014)
  • Author(s): Ogata F, Fujiu K, Koshima I, Nagai R, Manabe I.
  • Journal Title: Br J Dermatol. Volume: - Issue: 5 Pages: 1286-1293
  • DOI: 10.1111/bjd.13482
  • Peer Reviewed
• [Journal Article] Can intensive lipid-lowering therapy improve the carotid intima-media thickness in Japanese subjects under primary prevention for cardiovascular disease?: The JART and JART extension subanalysis. (2014)
  • Author(s): Daida H, Nohara R, Hata M, Kaku K, Kawamori R, Kishimoto J, Kurabayashi M, Masuda I, Sakuma I, Yamazaki T, Yokoi H, Yoshida M; Justification for Atherosclerosis Regression Treatment (JART) Investigators.
  • Journal Title: J Atheroscler Thromb. Volume: 21 Pages: 739-754
  • Peer Reviewed
• [Journal Article] The ω-3 polyunsaturated fatty acid, eicosapentaenoic acid, attenuates abdominal aortic aneurysm development via suppression of tissue remodeling. (2014)
  • Author(s): Wang JH, Eguchi K, Matsumoto S, Fujiu K, Komuro I, Nagai R, Manabe I.
  • Journal Title: PLoS One Volume: 5 Issue: 5 Pages: e96286-e96286
  • DOI: 10.1371/journal.pone.0096286
  • Peer Reviewed / Open Access
• [Journal Article] ardioprotective function of cardiac macrophages. (2014)
  • Author(s): Fujiu K, Wang J, Nagai R.
  • Journal Title: Cardiovasc Res. Volume: 102 Issue: 2 Pages: 232-239
  • DOI: 10.1093/cvr/cvu059
  • Peer Reviewed
• [Journal Article] Cardioprotective function of cardiac macrophage. (2014)
  • Author(s): Fujiu K, Wang J, Nagai R.
  • Journal Title: Cardiovasc Res. Volume: in press Pages: 64-73
  • DOI: 10.1016/j.yjmcc.2014.01.013
  • 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
• [Presentation] 心臓のマクロファージによる心臓老化制御 (2016)
  • Author(s): 藤生克仁
  • Organizer: 脳心血管抗加齢研究会
  • Place of Presentation: 秋葉原
  • Year and Date: 2016-12-18
  • Invited
• [Presentation] 臓器間連携による心臓恒常性維持機構 (2016)
  • Author(s): 藤生克仁
  • Organizer: 第20回日本心血管内分泌代謝学会学術総会
  • Place of Presentation: 東京
  • Year and Date: 2016-12-16
  • Invited
• [Presentation] Cardiac Macrophage is Required to Avoid Atrioventricular Block After Right Heart Pressure Overload (2016)
  • Author(s): Sugita J, Fujiu K, Nakayama Y, Matsubara T, Matsuda J, Manabe I, Komuro I
  • Organizer: Annual Scientific Session of American Heart Association
  • Place of Presentation: New Orleans, USA
  • Year and Date: 2016-11-13
  • Int'l Joint Research
• [Presentation] 臓器連関を介した心血管の恒常性維持機構 (2016)
  • Author(s): 藤生克仁
  • Organizer: 第31回日本糖尿病合併症学会
  • Place of Presentation: 仙台
  • Year and Date: 2016-10-08
  • Invited
• [Presentation] マクロファージ不全による心不全発症機序の解明 (2014)
  • Author(s): 藤生 克仁
  • Organizer: 第1回 iHFフォーラム
  • Place of Presentation: 東京
  • Year and Date: 2014-08-09
  • Invited
• [Presentation] 周術期における抗凝固療法 ～休薬は本当に必要か～ (2014)
  • Author(s): 藤生 克仁
  • Organizer: Young Doctor’s Meeting～NOAC最前線
  • Place of Presentation: 東京
  • Year and Date: 2014-07-22
  • Invited
• [Presentation] 炎症細胞による心臓制御機構 (2014)
  • Author(s): 藤生 克仁
  • Organizer: 関東・心血管フォーラム
  • Place of Presentation: 東京
  • Year and Date: 2014-06-28
  • Invited
• [Presentation] 臓器間連関とアンチアージング (2014)
  • Author(s): 藤生 克仁
  • Organizer: 第１４回抗加齢医学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2014-06-07
  • Invited
• [Book] 細胞, 心不全における細胞間および臓器間の相互作用 (2016)
  • Author(s): 藤生克仁
  • Total Pages: 4
  • Publisher: ニューサイエンス社
• [Book] Anti-aging Science, 心臓マクロファージによる心臓老化制御 (2016)
  • Author(s): 藤生克仁
  • Total Pages: 104
  • Publisher: メディカルレビュー社
• [Book] 心腎連関と交感神経、腎・高血圧の最新治療 (2014)
  • Author(s): 藤生克仁、真鍋一郎
  • Total Pages: 7
  • Publisher: フジメティカル出版
• [Book] 発作性上室性頻拍症への対応、medicina (2014)
  • Author(s): 藤生克仁
  • Total Pages: 4
  • Publisher: 医学書院
• [Remarks]
  • URL: http://plaza.umin.ac.jp/~manabe/
• [Remarks]
  • URL: http://plaza.umin.ac.jp/~utok-card/clinical/arrythmia