Alterations in cardiac macrophages in heart failure

• Project/Area Number: 16K15437
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Cardiovascular medicine
• Research Institution: Chiba University
• Principal Investigator: MANABE Ichiro 千葉大学, 大学院医学研究院, 教授 (70359628)
• Research Collaborator: FUJIU Katsuhito 東京大学, 医学部附属病院, 特任助教 (30422306) ; MATSUMOTO Sahohime 千葉大学, 大学院医学研究院, 特任助教 (80570184) ; NAKAYAMA Yukiteru 東京大学, 医学部附属病院, 助教 (70721885)
• Project Period (FY): 2016-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2016: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
• Keywords: マクロファージ / 心不全 / エピジェネティクス / エピゲノム

Outline of Final Research Achievements

Cardiac macrophages play various roles in the cardiac response to stress. In this study we hypothesized that the changes in cardiac macrophage function might contribute to the development of heart failure and that the changes might be regulated by the interaction between cardiac microenvironment and macrophages. We analyzed transcriptomes and epigenome in macrophages by RNA-seq and ATAC-seq and found that cardiac stress greatly altered epigenome in macrophages. We then identified several transcriptional regulatory motifs that may control epigenome in response to cardiac stress. We have also identified regulatory regions that respond to cardiac microenvironment and regulate cardiac macrophage-specific gene expression.

Research Products

• [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
• [Presentation] Immunometabolic Regulation of Cardiac Homeostasis and Heart Failure (2017)
  • Author(s): Manabe I
  • Organizer: The 19th Takeda Science Foundation Symposium on Bioscience
  • Place of Presentation: 武田薬品研修所（大阪府吹田市）
  • Int'l Joint Research / Invited
• [Presentation] 心臓－脳－腎臓連携による心臓恒常性の維持と心不全 (2016)
  • Author(s): 眞鍋一郎
  • Organizer: CVMW2016心血管代謝週間
  • Place of Presentation: 東京コンベンションホール（東京都中央区）
  • Invited
• [Presentation] Immune regulation of the cardiovascular system (2016)
  • Author(s): Manabe I
  • Organizer: 第39会日本高血圧学会総会
  • Place of Presentation: 仙台国際センター（宮城県仙台市）
  • Invited
• [Remarks]
  • URL: http://plaza.umin.ac.jp/~manabe/