the novel molecular mechanism of the regulation of cardiac macrophages

• Project/Area Number: 16K19387
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Cardiovascular medicine
• Research Institution: The University of Tokyo
• Principal Investigator: Nakayama Yukiteru 東京大学, 医学部附属病院, 助教 (70721885)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 心不全 / マクロファージ / 慢性炎症 / エピゲノム / 循環器・高血圧 / 発現制御 / 免疫学 / シグナル伝達

Outline of Final Research Achievements

Heart failure is still a disease with high morbidity and high mortality and the elucidation of the pathophysiology is imperative. We have previously revealed that murine cardiac resident macrophages are indispensable in homeostasis of heart, and Amphiregulin, which is expressed exclusively in cardiac macrophages has a cardio-protective role. I performed ATAC-seq of cardiac macrophages to analyze the transcriptional regulation of these cell-specific genes. As compared to heart failure model and aged mice, I found that the epigenome of cardiac macrophages has altered in the transition from fetal liver monocyte-derived to bone marrow monocyte-derived and with aging of bone marrow. I think the intervention to the molecular mechanism which led to these epigenomic changes could be the novel target of heart failure.

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] The H3K9 methyltransferase Setdb1 regulates TLR4-mediated inflammatory responses in macrophages. (2016)
  • Author(s): R. Hachiya, T. Shiihashi, I. Shirakawa, Y. Iwasaki, Y. Matsumura, Y. Oishi, Y. Nakayama, Y. Miyamoto, I. Manabe, K. Ochi, M. Tanaka, N. Goda, J. Sakai, T. Suganami, Y. Ogawa.
  • Journal Title: Sci. Rep. Volume: 6 Issue: 1 Pages: 28845-28845
  • DOI: 10.1038/srep28845
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Excess Lymphangiogenesis Cooperatively Induced by Macrophages and CD4D T Cells Drives the Pathogenesis of Lymphedema (2016)
  • Author(s): Ogata F
  • Journal Title: Journal of Investigative Dermatology Volume: 136 Issue: 3 Pages: 706-714
  • DOI: 10.1016/j.jid.2015.12.001
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [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: 第1回 日本循環器学会基礎研究フォーラム
• [Presentation] The Protective Roles of Cardiac Macrophages in Cardiac Function and the Mechanism of Regulation (2017)
  • Author(s): 中山 幸輝
  • Organizer: 第81回 日本循環器学会学術集会
  • Place of Presentation: 金沢
  • Year and Date: 2017-03-17
• [Presentation] The protective role of cardiac macrophages in cardiac function and the mechanism of regulation (2017)
  • Author(s): Yukiteru Nakayama, Katsuhito Fujiu, Ichiro Manabe, Issei Komuro
  • Organizer: Keystone Symposia Aging and Mechanisms of Aging-Related Disease
  • Int'l Joint Research
• [Presentation] he protective role of cardiac macrophages in cardiac function and the mechanism of regulation (2017)
  • Author(s): Yukiteru Nakayama, Katsuhito Fujiu, Ichiro Manabe, Issei Komuro
  • Organizer: 第34回 国際心臓研究学会日本部会
  • Int'l Joint Research
• [Presentation] 心臓組織マクロファージの心機能に与える影響と機能制御の解明 (2016)
  • Author(s): 中山 幸輝
  • Organizer: 第20回 日本心血管内分泌代謝学会
  • Place of Presentation: 東京
  • Year and Date: 2016-12-16
• [Presentation] 心臓マクロファージの心保護的作用とその制御機構 (2016)
  • Author(s): 中山 幸輝
  • Organizer: 第39回 日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2016-11-30
• [Presentation] the Role of long noncoding RNA expressed in pro-inflammatory macrophages (2016)
  • Author(s): 中山 幸輝
  • Organizer: 第24回 マクロファージ分子細胞生物学国際シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2016-06-04
  • Int'l Joint Research