Role of the novel myokine in cardiovascular disease

• Project/Area Number: 18K19541
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 53:Organ-based internal medicine and related fields
• Research Institution: Nagoya University
• Principal Investigator: Ouchi Noriyuki 名古屋大学, 医学系研究科, 特任教授 (00595514)
• Co-Investigator(Kenkyū-buntansha): 大橋 浩二 名古屋大学, 医学系研究科, 特任准教授 (10595515) ; 柴田 玲 名古屋大学, 医学系研究科, 特任教授 (70343689)
• Project Period (FY): 2018-06-29 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000); Fiscal Year 2019: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000); Fiscal Year 2018: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
• Keywords: 心血管病 / 運動 / 持久性運動

Outline of Final Research Achievements

We found that the Netrin (Ntn) family member/Ntn5 acts as an exercise-inducible muscle-derived secretory factor “myokine” in mice after screening of novel myokines which are upregulated in skeletal muscle by treadmill exercise training. Intramuscular injection of adenoviral vectors expressing Ntn5 significantly enhanced blood blow recovery in a mouse model of hindlimb ischemia. Thus, Ntn5 may be a pro-angiogenic myokine induced by endurance exercise.

Academic Significance and Societal Importance of the Research Achievements

本研究では、持久性運動により誘発され、血管新生を促進する新たな骨格筋由来分泌因子「マイオカイン」が明らかとなった。本研究は血管新生の病態解明につながる可能性があり学術的意義は高いと考えられる。また、このマイオカインは運動による心血管保護作用にも関わり、運動すれば何故体にいいのか？という疑問に対する解決の糸口になり得る可能性があり、さらなる研究の発展も期待され、社会的意義は高いと考えられる。

Research Products

• [Journal Article] A novel selective PPARα modulator, pemafibrate promotes ischemia-induced revascularization through the eNOS-dependent mechanisms. (2020)
  • Author(s): Kawanishi H, Ohashi K, Ogawa H, Otaka N, Takikawa T, Fang L, Ozaki Y, Takefuji M, Murohara T, Ouchi N.
  • Journal Title: PLoS One. Volume: 15 Issue: 6 Pages: e0235362-e0235362
  • DOI: 10.1371/journal.pone.0235362
  • Peer Reviewed / Open Access
• [Journal Article] C1q/TNF-Related Protein 9 Promotes Revascularization in Response to Ischemia via an eNOS-Dependent Manner (2020)
  • Author(s): Yamaguchi Shukuro、Shibata Rei、Ohashi Koji、Enomoto Takashi、Ogawa Hayato、Otaka Naoya、Hiramatsu-Ito Mizuho、Masutomi Tomohiro、Kawanishi Hiroshi、Murohara Toyoaki、Ouchi Noriyuki
  • Journal Title: Frontiers in Pharmacology Volume: 11 Pages: 1313-1313
  • DOI: 10.3389/fphar.2020.01313
  • Peer Reviewed / Open Access
• [Journal Article] Adipolin/C1q/Tnf-related protein 12 prevents adverse cardiac remodeling after myocardial infarction. (2020)
  • Author(s): Takikawa T, Ohashi K, Ogawa H, Otaka N, Kawanishi H, Fang L, Ozaki Y, Eguchi S, Tatsumi M, Takefuji M, Murohara T, Ouchi N.
  • Journal Title: PLoS One. Volume: 15 Issue: 12 Pages: e0243483-e0243483
  • DOI: 10.1371/journal.pone.0243483
  • Peer Reviewed / Open Access
• [Journal Article] Associations among circulating levels of follistatin-like 1, clinical parameters, and cardiovascular events in patients undergoing elective percutaneous coronary intervention with drug-eluting stents (2019)
  • Author(s): Aikawa Tatsuro、Shimada Kazunori、Miyauchi Katsumi、Miyazaki Tetsuro、Sai Eiryu、Ouchi Shohei、Kadoguchi Tomoyasu、Kunimoto Mitsuhiro、Joki Yusuke、Dohi Tomotaka、Okazaki Shinya、Isoda Kikuo、Ohashi Koji、Murohara Toyoaki、Ouchi Noriyuki、Daida Hiroyuki
  • Journal Title: PLOS ONE Volume: 14 Issue: 4 Pages: e0216297-e0216297
  • DOI: 10.1371/journal.pone.0216297
  • Peer Reviewed / Open Access
• [Journal Article] Cardiomyocytes capture stem cell-derived, anti-apoptotic microRNA-214 via clathrin-mediated endocytosis in acute myocardial infarction. (2019)
  • Author(s): Eguchi S, Takefuji M, Sakaguchi T, Ishihama S, Mori Y, Tsuda T, Takikawa T, Yoshida T, Ohashi K, Shimizu Y, Hayashida R, Kondo K, Bando YK, Ouchi N, Murohara T.
  • Journal Title: J Biol Chem. Volume: 294 Issue: 31 Pages: 11665-11674
  • DOI: 10.1074/jbc.ra119.007537
  • Peer Reviewed / Open Access
• [Journal Article] Roles of the Mesenchymal Stromal/Stem Cell Marker Meflin in Cardiac Tissue Repair and the Development of Diastolic Dysfunction. (2019)
  • Author(s): Hara A, Kobayashi H, Asai N, Saito S, Higuchi T, Kato K, Okumura T, Bando YK, Takefuji M, Mizutani Y, Miyai Y, Saito S, Maruyama S, Maeda K, Ouchi N, Nagasaka A, Miyata T, Mii S, Kioka N, Worthley DL, Murohara T, Takahashi M, Enomoto A.
  • Journal Title: Circ. Res. Volume: 125 Issue: 4 Pages: 414-430
  • DOI: 10.1161/circresaha.119.314806
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Protein Kinase N Promotes Stress-Induced Cardiac Dysfunction Through Phosphorylation of Myocardin-Related Transcription Factor A and Disruption of Its Interaction With Actin. (2019)
  • Author(s): Sakaguchi T, Takefuji M, Wettschureck N, Hamaguchi T, Amano M, Kato K, Tsuda T, Eguchi S, Ishihama S, Mori Y, Yura Y, Yoshida T, Unno K, Okumura T, Ishii H, Shimizu Y, Bando YK, Ohashi K, Ouchi N, Enomoto A, Offermanns S, Kaibuchi K, Murohara T.
  • Journal Title: Circulation. Volume: 140 Issue: 21 Pages: 1737-1752
  • DOI: 10.1161/circulationaha.119.041019
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Adipolin/CTRP12 protects against pathological vascular remodeling through suppression of smooth muscle cell growth and macrophage inflammatory response. (2019)
  • Author(s): Ogawa H, Ohashi K, Ito M, Shibata R, Kanemura N, Yuasa D, Kambara T, Matsuo K, Hayakawa S, Hiramatsu-Ito M, Otaka N, Kawanishi H, Yamaguchi S, Enomoto T, Abe T, Kaneko M, Takefuji M, Murohara T, Ouchi N.
  • Journal Title: Cardiovasc Res. Volume: in press Issue: 1 Pages: 237-249
  • DOI: 10.1093/cvr/cvz074
  • Peer Reviewed / Open Access
• [Journal Article] Myonectin Is an Exercise-Induced Myokine That Protects the Heart From Ischemia-Reperfusion Injury. (2018)
  • Author(s): Otaka N, Shibata R, Ohashi K, Uemura Y, Kambara T, Enomoto T, Ogawa H, Ito M, Kawanishi H, Maruyama S, Joki Y, Fujikawa Y, Narita S, Unno K, Kawamoto Y, Murate T, Murohara T, Ouchi N.
  • Journal Title: Circ Res. Volume: 123 Issue: 12 Pages: 1326-1338
  • DOI: 10.1161/circresaha.118.313777
  • Peer Reviewed
• [Presentation] Role of a novel anti-inflammatory adipokine adipolin in cardiovascular and metabolic regulation. (2020)
  • Author(s): Koji Ohashi, Noriyuki Ouchi, Hayato Ogawa, Toyoaki Murohara
  • Organizer: 第84回日本循環器学会総会
• [Presentation] 抗炎症性アディポサイトカイン「アディポリン」と心血管病 (2020)
  • Author(s): 大内乗有 大橋浩二 室原豊明
  • Organizer: 第52回日本動脈硬化学会総会・学術集会
• [Presentation] 運動誘発性マイオカイン「マイオネクチン」の虚血性心疾患における役割 (2020)
  • Author(s): 大内乗有 大橋浩二 室原豊明
  • Organizer: 第26回日本心臓リハビリテーション学会学術集会
• [Presentation] Adipolin/C1q/Tnf-related protein 12 attenuates adverse cardiac remodeling in a mouse model of myocardial infarction. (2019)
  • Author(s): Tomonobu Takikawa, Koji Ohashi, Lixin Fang, Hiroshi Kawanishi, Naoya Otaka, Hayato Ogawa, Toyoaki Murohara, Noriyuki Ouchi
  • Organizer: ESC Congress 2019
  • Int'l Joint Research
• [Presentation] 運動誘発性マイオカイン「マイオネクチン」の虚血性心疾患における役割 (2019)
  • Author(s): 大内乗有 大高直也 室原豊明
  • Organizer: 第51回日本動脈硬化学会総会・学術集会
• [Presentation] アディポサイトカイン「アディポリン」の心血管病における役割 (2018)
  • Author(s): 大内乗有、大橋浩二、室原豊明
  • Organizer: 第50回日本動脈硬化学会総会・学術集会
• [Presentation] Role of the adiponectin paralogs C1q/TNF-related proteins in cardiovascular disease. (2018)
  • Author(s): 大内乗有
  • Organizer: 6th Seoul International Congress of Endocrinology and Metabolism (SICEM 2018)
  • Int'l Joint Research / Invited
• [Presentation] Role of the novel adipokine in cardiovascular disease. (2018)
  • Author(s): 大内乗有
  • Organizer: International Academy of Cardiology, Annual Scientific Sessions 2018, 23rd World Congress on Heart Disease
  • Int'l Joint Research / Invited