Role of Pericardial Fat Immune Cells in Myocardial Infarction

• Project/Area Number: 18K08048
• 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: Keio University
• Principal Investigator: ANZAI Atsushi 慶應義塾大学, 医学部(信濃町), 助教 (50528164)
• 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: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 心筋梗塞 / 炎症 / 免疫応答 / 心外膜脂肪 / 免疫 / 心不全

Outline of Final Research Achievements

We identified that interleukin (IL)-3-expressing B cells expand in the pericardial fat in response to myocardial infarction in mice. IL-3 receptor is highly expressed in cardiac macrophages and inflammatory monocytes. In vitro experiments using bone marrow-derived macrophages further revealed that IL-3 stimulates them to produce inflammatory cytokines and chemokines such as IL-1beta, IL-6, and CCL2, suggesting that pericardial B cell-derived IL-3 accelerates infarct inflammation, thereby leading to poor outcomes.

Academic Significance and Societal Importance of the Research Achievements

循環器疾患における心外膜脂肪の意義を示した研究は少ない。本研究はIL-3を介した心外膜脂肪と心臓monocytes/macrophageのクロストークが梗塞後の過剰な炎症を誘導・増幅する機序を示すのみならず、心外膜脂肪がどのように循環器疾患に影響を与えるのかを明らかにする研究になり得る。さらにはヒト検体を用いた臨床研究へ発展する可能性を秘めており、心筋梗塞後心不全を予防する新規治療法開発に繋がる可能性がある。

Research Products

• [Journal Article] Time-Series Transcriptome Analysis Reveals the miR-27a-5p-<i>Ppm1l</i> Axis as a New Pathway Regulating Macrophage Alternative Polarization After Myocardial Infarction (2021)
  • Author(s): Shinichi Goto , Genki Ichihara , Yoshinori Katsumata , Seien Ko , Atsushi Anzai, Kohsuke Shirakawa, Jin Endo, Masaharu Kataoka , Hidenori Moriyama , Takahiro Hiraide, Hiroki Kitakata , Takayasu Kobayashi, Keiichi Fukuda , Motoaki Sano
  • Journal Title: Circulation Journal Volume: 85 Issue: 6 Pages: 929-938
  • DOI: 10.1253/circj.CJ-20-0783
  • NAID: 130008043200
  • ISSN: 1346-9843, 1347-4820
  • Year and Date: 2021-05-25
  • Peer Reviewed / Open Access
• [Journal Article] MerTK Expression and ERK Activation Are Essential for the Functional Maturation of Osteopontin-Producing Reparative Macrophages After Myocardial Infarction (2020)
  • Author(s): Kohsuke Shirakawa, Jin Endo , Masaharu Kataoka, Yoshinori Katsumata, Atsushi Anzai, Hidenori Moriyama, Hiroki Kitakata, Takahiro Hiraide, Seien Ko, Shinichi Goto, Genki Ichihara, Keiichi Fukuda, Tohru Minamino, Motoaki Sano
  • Journal Title: Journal of American Heart Association Volume: 9 Issue: 18
  • DOI: 10.1161/jaha.120.017071
  • Peer Reviewed / Open Access
• [Journal Article] Self-reactive CD4+ IL-3+ T cells amplify autoimmune inflammation in myocarditis by inciting monocyte chemotaxis (2019)
  • Author(s): Anzai A, Mindur JE, Halle L, Sano S, Choi JL, He S, McAlpine CS, Chan CT, Kahles F, Valet C, Fenn AM, Nairz M, Rattik S, Iwamoto Y, Fairweather D, Walsh K, Libby P, Nahrendorf M, Swirski FK
  • Journal Title: Journal of Experimental Medicine Volume: 216 Issue: 2 Pages: 369-383
  • DOI: 10.1084/jem.20180722
  • Peer Reviewed / Int'l Joint Research
• [Presentation] 細胞・臓器間炎症ネットワークから捉えた循環器病の病態解明 (2021)
  • Author(s): 安西 淳
  • Organizer: CVMW2021‐心血管代謝週間－
  • Invited
• [Presentation] 心筋梗塞後炎症ネットワークの理解 (2021)
  • Author(s): 安西 淳
  • Organizer: CVMW2020 心血管代謝週間
  • Invited
• [Presentation] Deciphering stromal-inflammatory cell crosstalk identifies a novel mechanism underlying post-infarction cardiac repair (2020)
  • Author(s): 安西 淳
  • Organizer: 第4回 BCVR2020 日本循環器学会