Elucidation of bioactive lipid mediators related to ischemia-reperfusion injury and development of novel treatment strategy

• Project/Area Number: 17K09579
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Kobe University
• Principal Investigator: Shinohara Masakazu 神戸大学, 医学研究科, 准教授 (80437483)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 虚血再灌流傷害 / 脂質メディエーター / 虚血再灌流障害

Outline of Final Research Achievements

Ischemia-reperfusion injury remains unsolved critical issue which lacks any specific prevention and treatment under the era of development in revascularization. Here, we found novel disease mechanisms of ischemia-reperfusion injury by comprehensively analyzing bioactive lipid metabolites (lipid mediators), which we have developed as LC/MS/MS system-based metabololipidomics. These findings unveil a detailed pathological mechanism of ischemia-reperfusion organ injury and suggest a novel therapeutic approach.

Academic Significance and Societal Importance of the Research Achievements

虚血再灌流傷害は、現在の医学では特異的な予防法・治療法が存在せず、臨床現場における重要な課題である。動脈硬化性疾患に由来する心筋梗塞や脳梗塞、さらには臓器移植におけるドナー臓器等では、虚血再灌流に陥った臓器そのものの傷害が生じる。また大血管手術・整形外科手術ならびに災害によって四肢末梢の広範な虚血が生じた場合、再灌流によって肺・腎臓・脳・肝臓等の遠隔臓器に深刻な臓器傷害を生じることが知られている。虚血再灌流傷害を新たな視点から見直し、新しい病態メカニズムを理解したうえで、新規の特異的予防法・治療法を確立することが強く求められている。

Research Products

• [Journal Article] In Vivo Imaging of Venous Thrombus and Pulmonary Embolism Using Novel Murine Venous Thromboembolism Model (2020)
  • Author(s): Okano Mitsumasa、Hara Tetsuya、Nishimori Makoto、Irino Yasuhiro、Satomi-Kobayashi Seimi、Shinohara Masakazu、Toh Ryuji、Jaffer Farouc A.、Ishida Tatsuro、Hirata Ken-ichi
  • Journal Title: JACC: Basic to Translational Science Volume: 5 Issue: 4 Pages: 344-356
  • DOI: 10.1016/j.jacbts.2020.01.010
  • NAID: 120006952759
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Elevated Serum Elaidic Acid Predicts Risk of Repeat Revascularization After Percutaneous Coronary Intervention in Japan (2019)
  • Author(s): Oshita Toshihiko、Toh Ryuji、Shinohara Masakazu、Mori Kenta、Irino Yasuhiro、Nagao Manabu、Hara Tetsuya、Otake Hiromasa、Ishida Tatsuro、Hirata Ken-ichi
  • Journal Title: Circulation Journal Volume: 83 Issue: 5 Pages: 1032-1038
  • DOI: 10.1253/circj.CJ-18-1175
  • NAID: 130007636975
  • ISSN: 1346-9843, 1347-4820
  • Year and Date: 2019-04-25
  • Peer Reviewed
• [Journal Article] Serum concentration of full-length- and carboxy-terminal fragments of endothelial lipase predicts future cardiovascular risks in patients with coronary artery disease (2019)
  • Author(s): Nagao Manabu、Miyashita Kazuya、Mori Kenta、Irino Yasuhiro、Toh Ryuji、Hara Tetsuya、Hirata Ken-ichi、Shinohara Masakazu、Nakajima Katsuyuki、Ishida Tatsuro
  • Journal Title: Journal of Clinical Lipidology Volume: 13 Issue: 5 Pages: 839-846
  • DOI: 10.1016/j.jacl.2019.07.007
  • NAID: 120007002630
  • Peer Reviewed
• [Journal Article] Effect of rosuvastatin and eicosapentaenoic acid on neoatherosclerosis: the LINK-IT Trial (2019)
  • Author(s): Kuroda K, Otake H, Shinohara M, Kuroda M, Tsuda S, Toba T, Nagano Y, Toh R, Ishida T, Shinke T, Hirata KI.
  • Journal Title: EuroIntervention Volume: 15 Issue: 12 Pages: e1099-e1106
  • DOI: 10.4244/eij-d-18-01073
  • Peer Reviewed / Open Access
• [Journal Article] Identification of novel serum markers for the progression of coronary atherosclerosis in WHHLMI rabbits, an animal model of familial hypercholesterolemia (2019)
  • Author(s): Shiomi Masashi、Takeda Hiroaki、Irino Yasuhiro、Kimura Norie、Yamada Satoshi、Kuniyoshi Nobue、Kikumori Akio、Koike Yu、Koike Tomonari、Yoshida Masaru、Izumi Yoshihiro、Shinohara Masakazu、Bamba Takeshi、Ishida Tatsuro
  • Journal Title: Atherosclerosis Volume: 284 Pages: 18-23
  • DOI: 10.1016/j.atherosclerosis.2019.02.020
  • NAID: 120006850489
  • Peer Reviewed
• [Journal Article] Gut Microbiome and Plasma Microbiome-Related Metabolites in Patients With Decompensated and Compensated Heart Failure (2018)
  • Author(s): Hayashi T, Yamashita T, Watanabe H, Kami K, Yoshida N, Tabata T, Emoto T, Sasaki N, Mizoguchi T, Irino Y, Toh R, Shinohara M, Okada Y, Ogawa W, Yamada T, Hirata K.
  • Journal Title: Circulation Journal Volume: 83 Issue: 1 Pages: 182-192
  • DOI: 10.1253/circj.CJ-18-0468
  • NAID: 130007550393
  • ISSN: 1346-9843, 1347-4820
  • Year and Date: 2018-12-25
  • Peer Reviewed / Open Access
• [Journal Article] Modulation of lipid mediator profile may contribute to amelioration of chronic inflammation in adipose tissue of obese mice by pioglitazone (2018)
  • Author(s): Okada Kumiko、Hosooka Tetsuya、Shinohara Masakazu、Ogawa Wataru
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 505 Issue: 1 Pages: 29-35
  • DOI: 10.1016/j.bbrc.2018.09.081
  • Peer Reviewed / Open Access
• [Journal Article] Pentose phosphate pathway activation via HSP27 phosphorylation by ATM kinase: A putative endogenous antioxidant defense mechanism during cerebral ischemia-reperfusion (2018)
  • Author(s): Yamamoto Yusuke、Hosoda Kohkichi、Imahori Taichiro、Tanaka Jun、Matsuo Kazuya、Nakai Tomoaki、Irino Yasuhiro、Shinohara Masakazu、Sato Naoko、Sasayama Takashi、Tanaka Kazuhiro、Nagashima Hiroaki、Kohta Masaaki、Kohmura Eiji
  • Journal Title: Brain Research Volume: 1687 Pages: 82-94
  • DOI: 10.1016/j.brainres.2018.03.001
  • Peer Reviewed
• [Remarks] 神戸大学大学院医学研究科 疫学分野
  • URL: http://www.med.kobe-u.ac.jp/pbheal/index.html
• [Remarks] 神戸大学大学院医学研究科 質量分析総合センター
  • URL: http://www.med.kobe-u.ac.jp/icms/icms/index.html