Role of the myocyte-derived secreted factor in ischemic heart disease

• Project/Area Number: 23390207
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Nagoya University
• Principal Investigator: OUCHI NORIYUKI 名古屋大学, 医学(系)研究科(研究院), 寄附講座教授 (00595514)
• Co-Investigator(Kenkyū-buntansha): OHASHI Koji 名古屋大学, 医学系研究科, 寄附講座助教 (10595515) ; SHIBATA Rei 名古屋大学, 医学系研究科, 特任講師 (70343689) ; MUROHARA Toyoaki 名古屋大学, 医学系研究科, 教授 (90299503)
• Project Period (FY): 2011-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥19,370,000 (Direct Cost: ¥14,900,000、Indirect Cost: ¥4,470,000); Fiscal Year 2013: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2012: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000); Fiscal Year 2011: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
• Keywords: 分子心臓病態学 / 虚血性心疾患

Research Abstract

We found that follistatin-like 1 (Fstl1) is protective against acute cardiac injury following ischemia-reperfusion (I/R). Administration of Fstl1 led to reduction of myocardial infarct size following I/R in vivo, which was accompanied by attenuation of inflammatory response and apoptosis in the ischemic heart. Furthermore, Fstl1 attenuated inflammatory reaction and apoptosis in cardiac myocytes by its ability to activate AMP-activated protein kinase pathway and inhibit bone morphogenetic protein-4 signaling pathway.

Research Products

• [Journal Article] Transcriptional regulation of an insulin-sensitizing adipokine adipolin/CTRP12 in adipocytes by Krüppel-like factor 15 (2013)
  • Author(s): Enomoto T, Ohashi K, Shibata R, Kambara T, Uemura Y, Yuasa D, Kataoka Y, Miyabe M, Matsuo K, Joki Y, Hayakawa S, Hiramatsu-Ito M, Ito M, Murohara T, Ouchi N
  • Journal Title: PLoS One Volume: 8(12) Issue: 12 Pages: e83183-e83183
  • DOI: 10.1371/journal.pone.0083183
  • Peer Reviewed
• [Journal Article] Adiponectin-mediated modulation of lymphatic vessel formation and lymphedema (2013)
  • Author(s): Shimizu Y, Shibata R, Ishii M, Ohashi K, Kambara T, Uemura Y, Yuasa D, Kataoka Y, Kihara S, Murohara T, Ouchi N
  • Journal Title: J Am Heart Assoc Volume: 2 Issue: 5
  • DOI: 10.1161/jaha.113.000438
  • Peer Reviewed
• [Journal Article] Therapeutic Reendothelialization by Induced Pluripotent Stem Cells After Vascular Injury (2013)
  • Author(s): Yamamoto T, Shibata R, Ishii M, Kanemura N, Kito T, Suzuki H, Miyake H, Maeda K, Tanigawa T, Ouchi N, Murohara T
  • Journal Title: Arterioscler Thromb Vasc Biol Volume: 33 Issue: 9 Pages: 2218-21
  • DOI: 10.1161/atvbaha.113.301313
  • Peer Reviewed
• [Journal Article] iPS cell sheets created by a novel magnetite tissue engineering method for reparative angiogenesis. (2013)
  • Author(s): Kito T, Shibata R, Ishii M, Suzuki H, Himeno T, Kataoka Y, Yamamura Y, Yamamoto T, Nishio N, Ito S, Numaguchi Y, Tanigawa T, Yamashita JK, Ouchi N, Honda H, Isobe K, Murohara T.
  • Journal Title: Sci Rep Volume: 11:3 Issue: 1 Pages: 1418-1418
  • DOI: 10.1038/srep01418
  • Peer Reviewed
• [Journal Article] Adipose-derived factor CTRP9 attenuates vascular smooth muscle cell proliferation and neointimal formation (2013)
  • Author(s): Uemura Y, Shibata R, Ohashi K, Enomoto T, Kambara T, Yamamoto T, Ogura Y, Yuasa D, Joki Y, Matsuo K, Miyabe M, Kataoka Y, Murohara T, Ouchi N
  • Journal Title: FASEB J Volume: 27 Issue: 1 Pages: 25-33
  • DOI: 10.1096/fj.12-213744
  • Peer Reviewed
• [Journal Article] Therapeutic impact of follistatin-like 1 on myocardial ischemic injury in preclinical animal models (2012)
  • Author(s): Ogura Y, Ouchi N, Ohashi K, Shibata R, Kataoka Y, Kambara T, Kito T, Maruyama S, Yuasa D, Matsuo K, Enomoto T, Uemura Y, Miyabe M, Ishii M, Yamamoto T, Shimizu Y, Walsh K, Murohara T
  • Journal Title: Circulation Volume: 126 Issue: 14 Pages: 1728-38
  • DOI: 10.1161/circulationaha.112.115089
  • Peer Reviewed
• [Journal Article] Omentin as a novel biomarker of metabolic risk factors (2012)
  • Author(s): Shibata R, Ouchi N, Takahashi R, Terakura Y, Ohashi K, Ikeda N, Higuchi A, Terasaki H, Kihara S, Murohara T
  • Journal Title: Diabetol Metab Syndr Volume: 4 Issue: 1 Pages: 37-37
  • DOI: 10.1186/1758-5996-4-37
  • Peer Reviewed
• [Journal Article] CTRP9 protects against myocardial injury following ischemia-reperfusion through AMPK-dependent mechanism (2012)
  • Author(s): Kambara T, Ohashi K, Shibata R, Ogura Y, Maruyama S, Enomoto T, Uemura Y, Shimizu Y, Yuasa D, Matsuo K, Miyabe M, Kataoka Y, Murohara T, Ouchi N
  • Journal Title: J Biol Chem Volume: 287 Issue: 23 Pages: 18965-73
  • DOI: 10.1074/jbc.m112.357939
  • Peer Reviewed
• [Journal Article] Fat-derived factor omentin stimulates endothelial cell function and ischemia-induced revascularization via an endothelial nitric oxide synthase-dependent mechanism (2012)
  • Author(s): Maruyama S, Shibata R, Kikuchi R, Izumiya Y, Rokutanda T, Araki S, Kataoka Y, Ohashi K, Daida H, Kihara S, Ogawa H, Murohara T, Ouchi N
  • Journal Title: J Biol Chem Volume: 287 Issue: 1 Pages: 408-17
  • DOI: 10.1074/jbc.m111.261818
  • Peer Reviewed
• [Journal Article] Adipolin/C1qdc2/CTRP12 protein functions as an adipokine that improves glucose metabolism (2011)
  • Author(s): Enomoto T, Ohashi K, Shibata R, Higuchi A, Maruyama S, Izumiya Y, Walsh K, Murohara T, Ouchi N
  • Journal Title: J Biol Chem Volume: 286 Issue: 40 Pages: 34552-8
  • DOI: 10.1074/jbc.m111.277319
  • Peer Reviewed
• [Journal Article] Adiponectin ameliorates doxorubicin-induced cardiotoxicity through an Akt dependent mechanism (2011)
  • Author(s): Maruyama S, Shibata R, Ohashi K, Ohashi T, Daida H, Walsh K, Murohara T, Ouchi N
  • Journal Title: J Biol Chem Volume: 286 Issue: 37 Pages: 32790-800
  • DOI: 10.1074/jbc.m111.245985
  • Peer Reviewed
• [Journal Article] Circulating omentin is associated with coronary artery disease in men (2011)
  • Author(s): Shibata R, Ouchi N, Kikuchi R, Takahashi R, Takeshita K, Kataoka Y, Ohashi K, Ikeda N, Kihara S, Murohara T
  • Journal Title: Atherosclerosis Volume: 219 Pages: 811-4
  • Peer Reviewed
• [Journal Article] Circulating omentin is associated with coronary artery disease in men. (2011)
  • Author(s): Shibata R, Ouchi N, Kikuchi R, Takahashi R, Takeshita K, Kataoka Y, Ohashi K, Ikeda N, Kihara S, Murohara T.
  • Journal Title: Atherosclerosis. Volume: 219 Issue: 2 Pages: 811-814
  • DOI: 10.1016/j.atherosclerosis.2011.08.017
  • Peer Reviewed
• [Presentation] アディポサイトカインと血管病 (2013)
  • Author(s): 大内乗有
  • Organizer: 第17回日本心不全学会学術集会
  • Place of Presentation: 大宮ソニックシティー(さいたま市)埼玉
  • Year and Date: 2013-11-29
• [Presentation] アディポサイトカインと心血管病 (2013)
  • Author(s): 大内乗有, 柴田玲, 大橋浩二, 室原豊明
  • Organizer: 第17回日本心血管内分泌代謝学会学術集会
  • Place of Presentation: 千里ライフサイエンスセンター(豊中市)大阪
  • Year and Date: 2013-11-22
• [Presentation] 高血圧合併症とアディポサイトカインの関連 (2013)
  • Author(s): 大内乗有, 柴田玲, 大橋浩二, 室原豊明
  • Organizer: 第21回日本血管生物医学会学術集会
  • Place of Presentation: 千里阪急ホテル(豊中市)大阪
  • Year and Date: 2013-09-28
• [Presentation] Role of adipocytokines in cardiovascular disease (2013)
  • Author(s): Ouchi N
  • Organizer: The 2nd International Congress on Lipid Metabolism & Atherosclerosis Seoul Korea
  • Year and Date: 2013-09-14
• [Presentation] Role of adipocytokines in the cardiovascular system (2012)
  • Author(s): Ouchi N
  • Organizer: The 29th Annual Meeting of the International Society for Heart Research Japanese Section Centennial Hall Kyushu University School of Medicine (Fukuoka) Fukuoka
  • Place of Presentation: Japan
  • Year and Date: 2012-10-27
• [Presentation] 心血管系における新規アディポサイトカインの役割 (2012)
  • Author(s): 大内乗有
  • Organizer: 第33回日本肥満学会
  • Place of Presentation: ホテルグランヴィア京都(京都市)京都
  • Year and Date: 2012-10-12
• [Presentation] アディポサイトカインによる炎症調節機構 (2012)
  • Author(s): 大内乗有
  • Organizer: 第44回日本動脈硬化学会総会
  • Place of Presentation: ヒルトン福岡シーホーク(福岡市)福岡
  • Year and Date: 2012-07-20
• [Presentation] アディポサイトカインによる疾患制御 (2012)
  • Author(s): 大内乗有
  • Organizer: 第49回日本臨床分子医学会学術集会
  • Place of Presentation: みやこめっせ(京都市)京都
  • Year and Date: 2012-04-13
• [Presentation] Regulation of inflammatory responses by adipocytokines (2011)
  • Author(s): Ouchi N
  • Organizer: 第19回日本血管生物医学会学術集会
  • Place of Presentation: 東京ステーションコンファレンス(東京)東京
  • Year and Date: 2011-12-09
• [Presentation] アディポサイトカインと糖代謝異常 (2011)
  • Author(s): 大内乗有
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 国立京都国際会館(京都市)京都
  • Year and Date: 2011-09-21
• [Presentation] アディポサイトカインと糖代謝異常 (2011)
  • Author(s): 大内乗有
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 京都
  • Invited
• [Presentation] Regulation of inflammatory responses by adipocytokines (2011)
  • Author(s): 大内乗有
  • Organizer: 第19回日本血管生物医学会学術集会
  • Place of Presentation: 東京
  • Invited
• [Presentation] Role of adipocytokines in cardiovascular disease.
  • Author(s): 大内乗有
  • Organizer: The 2nd International Congress on Lipid Metabolism & Atherosclerosis
  • Place of Presentation: ソウル（韓国）
  • Invited
• [Presentation] 高血圧合併症とアディポサイトカインの関連
  • Author(s): 大内乗有 柴田玲 大橋浩二 室原豊明
  • Organizer: 第21回日本血管生物医学会学術集会
  • Place of Presentation: 千里阪急ホテル（豊中市）
  • Invited
• [Presentation] アディポサイトカインと心血管病
  • Author(s): 大内乗有 柴田玲 大橋浩二 室原豊明
  • Organizer: 第17回日本心血管内分泌代謝学会学術集会
  • Place of Presentation: 千里ライフサイエンスセンター（豊中市）
  • Invited
• [Presentation] アディポサイトカインと血管病
  • Author(s): 大内乗有
  • Organizer: 第17回日本心不全学会学術集会
  • Place of Presentation: 大宮ソニックシティー（埼玉県さいたま市）
  • Invited
• [Presentation] アディポサイトカインによる炎症調節機構
  • Author(s): 大内乗有
  • Organizer: 第44回日本動脈硬化学会総会
  • Place of Presentation: 福岡
• [Presentation] アディポサイトカインによる疾患制御
  • Author(s): 大内乗有
  • Organizer: 第49回日本臨床分子医学会学術集会
  • Place of Presentation: 京都
  • Invited
• [Presentation] 心血管系における新規アディポサイトカインの役割
  • Author(s): 大内乗有
  • Organizer: 第33回日本肥満学会
  • Place of Presentation: 京都
  • Invited
• [Presentation] Role of adipocytokines in the cardiovascular system
  • Author(s): 大内乗有
  • Organizer: The 29th Annual Meeting of the International Society for Heart Research Japanese Section
  • Place of Presentation: 福岡
  • Invited