PPARgamma nanomedicine that promotes cardiac healing after acute myocardial infarction

• Project/Area Number: 17K09590
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Kyushu University
• Principal Investigator: Matoba Tetsuya 九州大学, 大学病院, 講師 (20448426)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 心筋梗塞 / 炎症 / マクロファージ / ナノテクノロジー / 急性心筋梗塞 / 核受容体 / ドラッグデリバリーシステム / 組織修復 / 循環器内科学

Outline of Final Research Achievements

In a mouse model, myocardial ischemia-reperfusion causes sequential inflammation by M1 pro-inflammatory macrophages and M2 tissue healing macrophages. A nano-medicine containing PPAR gamma agonist pioglitazone, injected at repefusion, reduced infarct size by skewing macrophage polarity toward less-inflammatory, resulting in an inhibition of left ventricular remodeling and improvement of prognosis in the mouse model.

Academic Significance and Societal Importance of the Research Achievements

この研究により、急性心筋梗塞病態における急性炎症と組織修復の制御による新しい疾病治療コンセプトを示すとともに、ナノ医薬プラットフォームの有用性を示すことができた。

Research Products

• [Journal Article] Nanoparticle incorporating Toll-like receptor 4 inhibitor attenuates myocardial ischaemia?reperfusion injury by inhibiting monocyte-mediated inflammation in mice (2019)
  • Author(s): Fujiwara Masaki、Matoba Tetsuya、Koga Jun-Ichiro、Okahara Arihide、Funamoto Daiki、Nakano Kaku、Tsutsui Hiroyuki、Egashira Kensuke
  • Journal Title: Cardiovascular Research Volume: 115 Issue: 7 Pages: 1244-1255
  • DOI: 10.1093/cvr/cvz066
  • Peer Reviewed
• [Journal Article] Peroxisome proliferator-activated receptor-gamma targeting nanomedicine promotes cardiac healing after acute myocardial infarction by skewing monocyte/macrophage polarization in preclinical animal models (2018)
  • Author(s): Tokutome Masaki、Matoba Tetsuya、Nakano Yasuhiro、Okahara Arihide、Fujiwara Masaki、Koga Jun-Ichiro、Nakano Kaku、Tsutsui Hiroyuki、Egashira Kensuke
  • Journal Title: Cardiovascular Research Volume: 115 Issue: 2 Pages: 419-431
  • DOI: 10.1093/cvr/cvy200
  • Peer Reviewed
• [Journal Article] Nanoparticle-mediated drug delivery system for atherosclerotic cardiovascular disease (2017)
  • Author(s): Matoba Tetsuya、Koga Jun-ichiro、Nakano Kaku、Egashira Kensuke、Tsutsui Hiroyuki
  • Journal Title: Journal of Cardiology Volume: 70 Issue: 3 Pages: 206-211
  • DOI: 10.1016/j.jjcc.2017.03.005
  • Peer Reviewed
• [Journal Article] Anti-inflammatory Nanomedicine for Cardiovascular Disease (2017)
  • Author(s): Katsuki Shunsuke、Matoba Tetsuya、Koga Jun-ichiro、Nakano Kaku、Egashira Kensuke
  • Journal Title: Frontiers in Cardiovascular Medicine Volume: 4 Pages: 1383-1395
  • DOI: 10.3389/fcvm.2017.00087
  • Peer Reviewed / Open Access
• [Presentation] Targeting Inflammation in Acute Myocardial Infarction. (2019)
  • Author(s): 的場哲哉、古賀純一郎、江頭健輔
  • Organizer: 第51回日本動脈硬化学会総会・学術集会（2019年7月11-12日、京都）
  • Invited
• [Presentation] 炎症をターゲットする新しい動脈硬化治療 (2019)
  • Author(s): 的場哲哉
  • Organizer: 第19回動脈硬化教育フォーラム教育講演（2019年2月3日、福岡）
  • Invited
• [Presentation] Targeting Cyclophilin D and Inflammation with Nano-medicines in Myocardial Ischemia-Reperfusion Injury. (2019)
  • Author(s): Tetsuya Matoba
  • Organizer: 3rd Annual 2019 International Hawaii Cardiovascular Symposium
  • Int'l Joint Research / Invited
• [Remarks] 九州大学循環器内科・冠動脈疾患・動脈硬化研究グループ
  • URL: https://www.cardiol.med.kyushu-u.ac.jp/research/ascvd/