The pathology of heart failure in elderly patients due to aging of hematopoietic stem cells

• Project/Area Number: 18K08061
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: The University of Tokyo
• Principal Investigator: Nakayama Yukiteru 東京大学, 医学部附属病院, 助教 (70721885)
• Co-Investigator(Kenkyū-buntansha): 藤生 克仁 東京大学, 医学部附属病院, 特任准教授 (30422306)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 心不全 / マクロファージ / 老化 / 加齢 / 造血幹細胞 / エピゲノム / 骨髄幹細胞

Outline of Final Research Achievements

Cardiac macrophages play indispensable roles in maintaining homeostatic conditions , and they can react against various external stresses in perturbed conditions. Aging would affect robustness of cardioprotective tissue macrophages in internal and external ways and induce intolerance to the following instability. In this project I hypothesized that age-related deteriorations of cardiac macrophages could lead to perturbation of cardiac tissue and impairment of cardiac function.

Academic Significance and Societal Importance of the Research Achievements

高齢化に伴って心不全の罹患率は増加し、医療経済を逼迫させている。一度心不全を発症し入院すると、入退院を繰り返し、最終的に心不全悪液質の状態となることである。いくつかの神経内分泌物質を対象とした薬物治療は収縮障害型心不全の予後を改善するが、いずれも対症療法に過ぎない。特に高齢者に多い拡張障害を主体とする心不全の治療法は乏しく、その病態すら分かっていない。したがって、現在、心不全の予後は不良であり、不治である。今回、心臓間質の免疫細胞の、加齢による細胞内因的な質的変化が心機能悪化を引き起こするという知見が得られ、新たな心不全の治療標的の同定に繋がると考えられた。

Research Products

• [Journal Article] Cardiac macrophages prevent sudden death during heart stress. (2021)
  • Author(s): Sugita J, Fujiu K, Nakayama Y, Matsubara T, Matsuda J, Oshima T, Liu Y, Maru Y, Hasumi E, Kojima T, Seno H, Asano K, Ishijima A, Tomii N, Yamazaki M, Kudo F, Sakuma I, Nagai R, Manabe I, Komuro I.
  • Journal Title: Nat Commun. Volume: 12(1) Issue: 1 Pages: 1910-1910
  • DOI: 10.1038/s41467-021-22178-0
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Symptomatic Right Ventricular Outflow Tract Obstruction Due to Sinus of Valsalva Aneurysm (2020)
  • Author(s): Saito Akihito、Soma Katsura、Masuzawa Akihiro、Hatsuse Satoshi、Nakayama Yukiteru、Amiya Eisuke、Yao Atsushi、Hirata Yasutaka、Komuro Issei
  • Journal Title: Circulation Journal Volume: 84 Issue: 12 Pages: 2324
  • DOI: 10.1253/circj.CJ-20-0554
  • NAID: 130007942490
  • ISSN: 1346-9843, 1347-4820
  • Year and Date: 2020-11-25
  • Peer Reviewed
• [Journal Article] A long noncoding RNA regulates inflammation resolution by mouse macrophages through fatty acid oxidation activation (2020)
  • Author(s): Nakayama Yukiteru、Fujiu Katsuhito、Yuki Ryuzaburo、Oishi Yumiko、Morioka Masaki Suimye、Isagawa Takayuki、Matsuda Jun、Oshima Tsukasa、Matsubara Takumi、Sugita Junichi、Kudo Fujimi、Kaneda Atsushi、Endo Yusuke、Nakayama Toshinori、Nagai Ryozo、Komuro Issei、Manabe Ichiro
  • Journal Title: Proceedings of the National Academy of Sciences Volume: 117 Issue: 25 Pages: 14365-14375
  • DOI: 10.1073/pnas.2005924117
  • Peer Reviewed / Open Access
• [Journal Article] Effects of Adipocyte Expansion on Cardiovascular System and Ongoing Debate over Obesity Paradox (2019)
  • Author(s): Nakayama Yukiteru、Fujiu Katsuhito
  • Journal Title: International Heart Journal Volume: 60 Issue: 3 Pages: 499-502
  • DOI: 10.1536/ihj.19-140
  • NAID: 130007655769
  • ISSN: 1349-2365, 1349-3299
  • Year and Date: 2019-05-30
  • Peer Reviewed / Open Access
• [Journal Article] Maladaptive Alterations of Autonomic Nerve System in Cardiovascular Disorders (2019)
  • Author(s): Yukiteru Nakayama, Katsuhito Fujiu
  • Journal Title: International Heart Journal Volume: 60 Issue: 1 Pages: 4-6
  • DOI: 10.1536/ihj.18-677
  • NAID: 130007557185
  • ISSN: 1349-2365, 1349-3299
  • Year and Date: 2019-01-31
  • Peer Reviewed / Open Access
• [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
• [Presentation] The protective role of cardiac macrophages in cardiac function and the mechanism of regulation (2018)
  • Author(s): Yukiteru Nakayama, Katsuhito Fujiu, Ichiro Manabe, Issei Komuro
  • Organizer: Cell Symposia; Aging and Metabolism
  • Int'l Joint Research
• [Presentation] Hematopoietic stem cells in pathological conditions are detrimental to cardiac function via the impairment of differentiation to cardiac macrophages (2018)
  • Author(s): Yukiteru Nakayama, Katsuhito Fujiu, Ichiro Manabe, Issei Komuro
  • Organizer: 第35回 国際心臓研究学会日本部会
• [Book] 実験医学増刊 Vol.37 No.5 心不全のサイエンス (2018)
  • Author(s): 中山幸輝, 藤生克仁
  • Total Pages: 8
  • Publisher: 羊土社
  • ISBN: 9784758103770