New Experimental Model of Cardiac Function Recovery

• Project/Area Number: 18H02360
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 42040:Laboratory animal science-related
• Research Institution: The University of Tokyo
• Principal Investigator: SEMBA HIROAKI 東京大学, 医学部附属病院, 届出研究員 (80747923)
• Co-Investigator(Kenkyū-buntansha): 武田 憲彦 自治医科大学, 医学部, 教授 (40422307)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000); Fiscal Year 2020: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2019: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2018: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
• Keywords: 心不全 / 心肥大 / 心臓線維化 / 心臓線維芽細胞 / マクロファージ / Reverse TAC / ReverseTAC / リバースリモデリング

Outline of Final Research Achievements

Heart failure is a condition in which the pumping function of the heart is impaired. Traditional experimental models used to study heart failure have been suitable for analyzing how heart failure develops and progresses. In this study, we aimed to analyze how heart failure improves and recovers with a new experimental model. And we have shown that macrophages, which control inflammatory process, play an important role not only in the onset and progression but also in the improvement and recovery of heart failure.

Academic Significance and Societal Importance of the Research Achievements

心不全は、心臓のポンプ機能が失われる状態のことであり、あらゆる心臓病の終末像とも言えます。心不全の患者数は日本のみならず世界中で増え続けており、健康上の大きな問題になっています。これまでの心不全の研究は、主にその発症・進展のメカニズムについて解析するものでしたが、実際に心不全を診療する臨床の現場では改善・回復のメカニズムを解明することが求められてきました。本研究は、そのような実際の心不全診療のニーズに迫るものであり、社会的意義を有するものと考えられます。

Research Products

• [Journal Article] Establishment of Novel Protein Interaction Assays between Sin3 and REST Using Surface Plasmon Resonance and Time-Resolved Fluorescence Energy Transfer (2021)
  • Author(s): Harada, M., Nagai, J., Kurata, R., Cui, X., Isagawa, T., Semba, H., ... & Yonezawa, T.
  • Journal Title: International journal of molecular sciences Volume: 22(5) Issue: 5 Pages: 2323-2323
  • DOI: 10.3390/ijms22052323
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Hypoxia-inducible factor-1 alpha maintains mouse articular cartilage through suppression of NF-κB signaling (2020)
  • Author(s): Okada Keita、Mori Daisuke、Makii Yuma、Nakamoto Hideki、Murahashi Yasutaka、Yano Fumiko、Chang Song Ho、Taniguchi Yuki、Kobayashi Hiroshi、Semba Hiroaki、Takeda Norihiko、Piao Wen、Hanaoka Kenjiro、Nagano Tetsuo、Tanaka Sakae、Saito Taku
  • Journal Title: Scientific Reports Volume: 10 Issue: 1 Pages: 5425-5425
  • DOI: 10.1038/s41598-020-62463-4
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Establishment of Novel High-Standard Chemiluminescent Assay for NTPase in Two Protozoans and Its High-Throughput Screening (2020)
  • Author(s): Masamitsu Harada, Jun Nagai, Riho Kurata, Kenji Shimizu, Xiaofeng Cui, Takayuki Isagawa, Hiroaki Semba, Jun Ishihara, Yasuhiro Yoshida, Norihiko Takeda, Koji Maemura, Tomo Yonezawa
  • Journal Title: Marine Drugs Volume: 18 Issue: 3 Pages: 161-161
  • DOI: 10.3390/md18030161
  • NAID: 120006988256
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Novel Reporter System Monitoring IL-18 Specific Signaling Can Be Applied to High-Throughput Screening (2020)
  • Author(s): Kurata R, Shimizu K, Cui X, Harada M, Isagawa T, Semba H, Ishihara J, Yamada K, Nagai J, Yoshida Y, Takeda N, Maemura K, Yonezawa T.
  • Journal Title: Marine Drugs Volume: 18 Issue: 1 Pages: 60-60
  • DOI: 10.3390/md18010060
  • NAID: 120006988310
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Macrophage hypoxia signaling regulates cardiac fibrosis via Oncostatin M. (2019)
  • Author(s): Abe H, Takeda N, Isagawa T, Semba H, Nishimura S, Morioka MS, Nakagama Y, Sato T, Soma K, Koyama K, Wake M, Katoh M, Asagiri M, Neugent ML, Kim JW, Stockmann C, Yonezawa T, Inuzuka R, Hirota Y, Maemura K, Yamashita T, Otsu K, Manabe I, Nagai R, Komuro I.
  • Journal Title: Nature Communications Volume: 10 Issue: 1 Pages: 2824-2833
  • DOI: 10.1038/s41467-019-10859-w
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Establishment of novel cells stably secreting various human IL-18 recombinant proteins. (2019)
  • Author(s): Asuka Kumagai, Kenji Shimizu, Riho Kurata, Xiaofeng Cui, Takayuki Isagawa, Msamitsu Harada, Jun Nagai, Yasuhiro Yoshida, Kei-ichi Ozaki, Norihiko Takeda, Hiroaki Semba and Tomo Yonezawa
  • Journal Title: Current Pharmaceutical Biotechnology Volume: 20 Issue: 1 Pages: 47-55
  • DOI: 10.2174/1389201020666190206203640
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] External suture annuloplasty for mild to moderate and moderate aortic regurgitation due to an isolated type Ic lesion (2019)
  • Author(s): Matsuhama Minoru、Arimura Satoshi、Sasaki Kenichi、Semba Hiroaki、Kato Yuko、Suzuki Shinya、Uejima Tokuhisa、Yajima Junji、Yamashita Takeshi、Kunihara Takashi
  • Journal Title: General Thoracic and Cardiovascular Surgery Volume: - Issue: 10 Pages: 855-860
  • DOI: 10.1007/s11748-019-01119-1
  • Peer Reviewed
• [Journal Article] Relationship between age and maximal heart rate in atrial fibrillation (2019)
  • Author(s): Kato Yuko、Suzuki Shinya、Uejima Tokuhisa、Semba Hiroaki、Arita Takuto、Yagi Naoharu、Kano Hiroto、Matsuno Shunsuke、Otsuka Takayuki、Oikawa Yuji、Matsuhama Minoru、Yajima Junji、Yamashita Takeshi
  • Journal Title: European Journal of Preventive Cardiology Volume: - Issue: 7 Pages: 780-782
  • DOI: 10.1177/2047487318823109
  • Peer Reviewed
• [Journal Article] Eleven-year temporal trends of clinical characteristics and long-term outcomes in patients undergoing percutaneous coronary intervention for acute coronary syndrome in the Shinken database (2018)
  • Author(s): Numao Yoshimi、Suzuki Shinya、Kano Hiroto、Yajima Junji、Oikawa Yuji、Matsuno Shunsuke、Arita Takuto、Yagi Naoharu、Semba Hiroaki、Kato Yuko、Otsuka Takayuki、Uejima Tokuhisa、Yamashita Takeshi
  • Journal Title: Heart and Vessels Volume: 34 Issue: 2 Pages: 199-207
  • DOI: 10.1007/s00380-018-1229-y
  • Peer Reviewed
• [Journal Article] The predictive role of E / e ′ on ischemic stroke and atrial fibrillation in Japanese patients without atrial fibrillation (2018)
  • Author(s): Arai Riku、Suzuki Shinya、Semba Hiroaki、Arita Takuto、Yagi Naoharu、Otsuka Takayuki、Sagara Koichi、Sasaki Kenichi、Kano Hiroto、Matsuno Shunsuke、Kato Yuko、Uejima Tokuhisa、Oikawa Yuji、Kunihara Takashi、Yajima Junji、Yamashita Takeshi
  • Journal Title: Journal of Cardiology Volume: 72 Issue: 1 Pages: 33-41
  • DOI: 10.1016/j.jjcc.2018.01.001
  • Peer Reviewed / Open Access
• [Journal Article] Variable prognostic value of blood pressure response to exercise (2018)
  • Author(s): Kato Yuko、Suzuki Shinya、Uejima Tokuhisa、Semba Hiroaki、Yamashita Takeshi
  • Journal Title: Journal of Cardiology Volume: 71 Issue: 1 Pages: 31-35
  • DOI: 10.1016/j.jjcc.2017.07.004
  • Peer Reviewed / Open Access
• [Journal Article] Impact of Atrial Fibrillation on Falls in Older Patients: Which is a Problem, Existence or Persistence? (2018)
  • Author(s): Arita Takuto、Suzuki Shinya、Yagi Naoharu、Otsuka Takayuki、Semba Hiroaki、Kano Hiroto、Matsuno Shunsuke、Kato Yuko、Uejima Tokuhisa、Oikawa Yuji、Matsuhama Minoru、Yajima Junji、Yamashita Takeshi
  • Journal Title: Journal of the American Medical Directors Association Volume: - Issue: 6 Pages: 765-769
  • DOI: 10.1016/j.jamda.2018.10.008
  • Peer Reviewed / Open Access
• [Journal Article] Prognostic value of the heart rate profile during exercise in patients with atrial fibrillation (2018)
  • Author(s): Aihara Kazufumi、Kato Yuko、Suzuki Shinya、Arita Takuto、Yagi Naoharu、Semba Hiroaki、Kano Hiroto、Matsuno Shunsuke、Otsuka Takayuki、Uejima Tokuhisa、Oikawa Yuji、Kunihara Takashi、Yajima Junji、Yamashita Takeshi
  • Journal Title: European Journal of Preventive Cardiology Volume: 25 Issue: 15 Pages: 1634-1641
  • DOI: 10.1177/2047487318797398
  • Peer Reviewed
• [Journal Article] Relationship between the prognostic value of ventilatory efficiency and age in patients with heart failure (2018)
  • Author(s): Kato Yuko、Suzuki Shinya、Uejima Tokuhisa、Semba Hiroaki、Nagayama Osamu、Hayama Etsuko、Arita Takuto、Yagi Naoharu、Kano Hiroto、Matsuno Shunsuke、Otsuka Takayuki、Oikawa Yuji、Kunihara Takashi、Yajima Junji、Yamashita Takeshi
  • Journal Title: European Journal of Preventive Cardiology Volume: 25 Issue: 7 Pages: 731-739
  • DOI: 10.1177/2047487318758775
  • Peer Reviewed
• [Presentation] Oncostatin M from hypoxic macrophage inhibits cardiac fibrosis in vivo (2019)
  • Author(s): Hiroaki Semba
  • Organizer: Venice Arrhythmias 2019
  • Int'l Joint Research
• [Presentation] Hypoxic Macrophage Derived Oncostatin-M inhibits cardiac fibrosis (2019)
  • Author(s): Hiroaki Semba
  • Organizer: 33rd Annual Conference EMDS 2019
  • Int'l Joint Research
• [Presentation] Hypoxic macrophages suppress cardiac fibrosis via oncostatin M in vivo. (2019)
  • Author(s): Hiroaki Semba
  • Organizer: 14th World Congress on Inflammation 2019
  • Int'l Joint Research
• [Presentation] Oncostatin-M suppresses cardiac fibrosis in vivo (2018)
  • Author(s): Hiroaki Semba
  • Organizer: The 82nd Annual Scientific Meeting of the Japanese Circulation Society