The potential of omentin as therapeutic agents for cardiovascular disease.

• Project/Area Number: 17K09572
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Nagoya University
• Principal Investigator: Shibata Rei 名古屋大学, 医学系研究科, 特任教授 (70343689)
• Co-Investigator(Kenkyū-buntansha): 大内 乗有 名古屋大学, 医学系研究科, 寄附講座教授 (00595514) ; 室原 豊明 名古屋大学, 医学系研究科, 教授 (90299503)
• 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: ¥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: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: オメンチン / 心筋梗塞 / リモデリング / 虚血性心疾患

Outline of Final Research Achievements

Adipose tissue functions as an endocrine organ by secreting adipokines that can directly affect nearby or remote organs. Omentin is an adipokine whose concentration is down-regulated in subjects with obesity-related disorders. In our study, we have shown that transgenic mice expressing the human omentin gene in fat tissue mice exhibit a significant decrease in mortality and improvement of cardiac function following myocardial infarction. Adipose-derived omentin prevents pathological cardiac remodeling after chronic ischemia, suggesting that omentin represents a potential therapeutic molecule for the treatment of ischemic heart disease.

Academic Significance and Societal Importance of the Research Achievements

高齢化社会の到来により、心臓疾患の患者数は顕著に増加しているのみならず、死亡率も非常に高い。まだまだ新たな治療法が求められている現状である。今回我々は、オメンチンが虚血下において直接的な心保護効果を有することをマウス及びミニブタを用いた検討にて見出している。これらの所見は、オメンチンを標的とした新たな心血管病治療の開発につながると考えている。

Research Products

• [Journal Article] Utility of the Nutritional Screening in Predicting Adverse Outcome of Patients With Overweight/Obesity and Acute Heart Failure (2020)
  • Author(s): UEMURA YUSUKE、SHIBATA REI、MASUDA AKIHIRO、KATSUMI YUTA、TAKEMOTO KENJI、KOYASU MASAYOSHI、ISHIKAWA SHINJI、MITSUDA TAKAYUKI、MUROHARA TOYOAKI、WATARAI MASATO
  • Journal Title: Journal of Cardiac Failure Volume: - Issue: 7 Pages: 566-573
  • DOI: 10.1016/j.cardfail.2020.02.005
  • Peer Reviewed
• [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] Angiotensin-converting enzyme inhibitors versus angiotensin receptor blockers in hypertensive patients with myocardial infarction or heart failure: a systematic review and meta-analysis (2019)
  • Author(s): Ohtsubo T、Shibata R、Kai H、Okamoto R、Kumagai E、Kawano H、Fujiwara A、Kitazono T、Murohara T、Hisatomi A
  • Journal Title: Hypertension Research Volume: 42 Issue: 5 Pages: 641-649
  • DOI: 10.1038/s41440-018-0167-5
  • Peer Reviewed
• [Journal Article] Alteration in ventricular pressure stimulates cardiac repair and remodeling (2019)
  • Author(s): Unno Kazumasa、Oikonomopoulos Angelos、Fujikawa Yusuke、Okuno Yusuke、Narita Singo、Kato Tomohiro、Hayashida Ryo、Kondo Kazuhisa、Shibata Rei、Murohara Toyoaki、Yang Yanfei、Dangwal Seema、Sereti Konstantina-Ioanna、Yiling Qiu、Johnson Kory、Jha Alokkumar、Sosnovik David E.、Fann Yang、Liao Ronglih
  • Journal Title: Journal of Molecular and Cellular Cardiology Volume: 133 Pages: 174-187
  • DOI: 10.1016/j.yjmcc.2019.06.006
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Importance of sodium-glucose cotransporter 2 inhibitor use in diabetic patients with acute heart failure (2019)
  • Author(s): Kambara Takahiro、Shibata Rei、Osanai Hiroyuki、Nakashima Yoshihito、Asano Hiroshi、Murohara Toyoaki、Ajioka Masayoshi
  • Journal Title: Therapeutic Advances in Cardiovascular Disease Volume: 13
  • DOI: 10.1177/1753944719894509
  • Peer Reviewed / Open Access
• [Journal Article] Prothrombotic Responses After Catheter Ablation for Atrial Fibrillation During Uninterrupted Oral Anticoagulant Agent Administration (2019)
  • Author(s): Yanagisawa Satoshi、Inden Yasuya、Fujii Aya、Sakamoto Yusuke、Tomomatsu Toshiro、Mamiya Keita、Okamoto Hiroya、Shibata Rei、Murohara Toyoaki
  • Journal Title: JACC: Clinical Electrophysiology Volume: 5 Issue: 12 Pages: 1418-1427
  • DOI: 10.1016/j.jacep.2019.09.002
  • Peer Reviewed
• [Journal Article] Prognostic Impact of the Preservation of Activities of Daily Living on Post-Discharge Outcomes in Patients With Acute Heart Failure (2018)
  • Author(s): Uemura Yusuke、Shibata Rei、Takemoto Kenji、Koyasu Masayoshi、Ishikawa Shinji、Murohara Toyoaki、Watarai Masato
  • Journal Title: Circulation Journal Volume: 82 Issue: 11 Pages: 2793-2799
  • DOI: 10.1253/circj.CJ-18-0279
  • NAID: 40021697233
  • ISSN: 1346-9843, 1347-4820
  • Year and Date: 2018-10-25
  • Peer Reviewed
• [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
• [Journal Article] Adiponectin/AdiopR1 signal inactivation contributes to impaired angiogenesis in mice of advanced age (2018)
  • Author(s): Piao Limei、Yu Chenglin、Xu Wenhu、Inoue Aiko、Shibata Rei、Li Xiang、Nan Yongshan、Zhao Guangxian、Wang Hailong、Meng Xiangkun、Lei Yanna、Goto Hiroki、Ouchi Noriyuki、Murohara Toyoaki、Kuzuya Masafumi、Cheng Xian Wu
  • Journal Title: International Journal of Cardiology Volume: 267 Pages: 150-155
  • DOI: 10.1016/j.ijcard.2018.05.089
  • Peer Reviewed / Open Access
• [Journal Article] The role of adipokines in cardiovascular disease. (2017)
  • Author(s): Shibata R, Ouchi N, Ohashi K, Murohara T.
  • Journal Title: J Cardiol. Volume: 17 Issue: 4 Pages: 30060-6
  • DOI: 10.1016/j.jjcc.2017.02.006
  • NAID: 130006887060
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] C1q/TNF-related protein 1 prevents neointimal formation after arterial injury. (2017)
  • Author(s): Kanemura N, Shibata R, Ohashi K, Ogawa H, Hiramatsu-Ito M, Enomoto T, Yuasa D, Ito M, Hayakawa S, Otaka N, Murohara T, Ouchi N.
  • Journal Title: Atherosclerosis. Volume: 257 Pages: 138-145
  • DOI: 10.1016/j.atherosclerosis.2017.01.014
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Chronic Psychological Stress Accelerates Vascular Senescence and Impairs Ischemia-Induced Neovascularization: The Role of Dipeptidyl Peptidase-4/Glucagon-Like Peptide-1-Adiponectin Axis. (2017)
  • Author(s): Piao L, Zhao G, Zhu E, Inoue A, Shibata R, Lei Y, Hu L, Yu C, Yang G, Wu H, Xu W, Okumura K, Ouchi N, Murohara T, Kuzuya M, Cheng XW.
  • Journal Title: J Am Heart Assoc. Volume: 28
  • Peer Reviewed / Open Access
• [Presentation] Efficacy and safety of SGLT2 inhibitors in elderly diabetic patients with heart failure (2019)
  • Author(s): Rei Shibata, Takahiro Kambara, Toyoaki Murohara, Masayoshi Ajioka
  • Organizer: 第83回日本循環器学会
  • Invited
• [Presentation] CTRPファミリータンパク質と循環器疾患 (2019)
  • Author(s): 柴田玲
  • Organizer: 第55回日本循環器病予防学会
  • Invited
• [Presentation] CTRPファミリータンパク質による血管病制御機構 (2019)
  • Author(s): 柴田玲
  • Organizer: 第47回日本血管外科学会学術総会
  • Invited
• [Presentation] 運動誘発性マイオカイン「マイオネクチン」の心血管病における役割 (2019)
  • Author(s): 柴田玲
  • Organizer: 第19回日本NO学会学術集会
  • Invited
• [Presentation] 心血管リモデリングにおけるCTRPファミリータンパク質の役割 (2018)
  • Author(s): 柴田玲
  • Organizer: 第66回日本心臓病学会学術集会
  • Invited
• [Presentation] The role of exercise-induced myokine, myonectin in cardiac ischemic injury (2018)
  • Author(s): Rei Shibata
  • Organizer: 第35回国際心臓研究学会日本部会
  • Int'l Joint Research / Invited
• [Presentation] 重症虚血肢に対する新たな治療戦略 (2018)
  • Author(s): 柴田玲
  • Organizer: 脳心血管抗加齢研究会2018
  • Invited
• [Presentation] Diabetes, obesity, metabolic syndrome & aging population- Japan (2017)
  • Author(s): Rei Shibata
  • Organizer: Asian Pacific Society of Cardiology 2017
  • Int'l Joint Research / Invited
• [Presentation] Therapeutic angiogenesis for critical limb ischemia by implantation of adipose-derived regenerative cells (2017)
  • Author(s): Rei Shibata
  • Organizer: The 26th Annual Scientific Meeting of Indonesian Heart Association
  • Int'l Joint Research / Invited