A novel mechanism for remote ischemic preconditioning

2012 Fiscal Year Final Research Report

• Project/Area Number: 23792094
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Emergency medicine
• Research Institution: Kurume University
• Principal Investigator: OBA Toyoharu 久留米大学, 医学部, 助教 (10389257)
• Project Period (FY): 2011 – 2012
• Keywords: シグナル伝達、 / 心筋保護 / 、サイトカイン、 / 神経調節、 / 臓器連関

Research Abstract

Remote ischemic preconditioning (RIPC) induced by brief episodesof blood flow occlusion applied in limbs is a powerful innate mechanism of cardiacprotection against ischemia. Mechanisms for the cardiac RIPC have not been fullyelucidated. Here we propose a novel mechanism of RIPC; renal nerve plays an importantrole in cardioprotection after myocardial infarction (MI) by releasing erythropoietin(EPO) production from the kidney. In mice transient limb ischemia decreased renal bloodflow (RBF), upregulated hypoxia-inducible factor-1α (HIF1α) and EPO mRNA in the kidney,and increased the plasma EPO level. Transient limb ischemia activated cardioprotectivesignaling pathways and anti-apoptotic pathways in the heart, and reduced infarct size,which were abolished by administration of an EPO neutralizing antibody. Renal nerve denervation also abolished the transient limb ischemia-induced RBF reduction, EPOproduction, and cardioprotection. In humans, Transient limb ischemia of the upper armdecreased RBF and increased plasma EPO levels. Taken together, our data suggest thatcardioprotection by transient limb ischemia is produced through renal nerve?mediatedreduction of RBF associated with activation of the HIF1α-EPO pathway.

Research Products

• [Journal Article] Cardiac-Specific Deletion ofSOCS-3 Prevents Development of LeftVentricular Remodeling After AcuteMyocardial Infarction. (2012)
  • Author(s): Oba T, Yasukawa H, Hoshijima M, SasakiKI, Futamata N, Fukui D, Mawatari K, NagataT, Kyogoku, S, Ohshima H, Minami T,Nakamura K, Kang D, Yajima T, Knowlton KU,Imaizumi T
  • Journal Title: J Am Coll Cardiol Volume: 59 Pages: 838-852
  • Peer Reviewed
• [Journal Article] Cardiomyocyte-specific transgenic expression of lysyl oxidase-like protein-1 induces cardiac hypertrophy in mice. (2012)
  • Author(s): Ohmura H, Yasukawa H, Minami T, Sugi Y, Oba T, Nagata T, Kyougoku S, Ohshima H, Aoki H, Imaizumi T
  • Journal Title: Hypertens Res Volume: 35 Pages: 1063-1068
  • Peer Reviewed
• [Journal Article] Transient reduction and activation ofcirculating dendritic cells in patientswith acute myocardial infarction. (2012)
  • Author(s): Fukui D, Yasukawa H, Sugi Y, Nagata T,Kyogoku S, Futamata N, Oba T, Yokoyama T,Yokoyama S, Ueno T, Kage M, Imaizumi T
  • Journal Title: Int J Cardiol Volume: 160 Pages: 216-219
  • Peer Reviewed
• [Journal Article] a novel therapeutic target forcardioprotection. (2012)
  • Author(s): Yasukawa H, Nagata T, Oba T, ImaizumiT: SOCS3
  • Journal Title: Jak-Stat Volume: 1 Pages: 234-240
  • Peer Reviewed
• [Journal Article] Screening for Fabry disease in patientswith left ventricular hypertrophy.
  • Author(s): Mawatari K, Yasukawa H, Oba T, Nagata T, Togawa T, Tsukimura T, KyogokuS, Ohshima H, Minami T, Sakubaba H,Imaizumi T.
  • Journal Title: Int J Cardiol Volume: (in press)
  • Peer Reviewed
• [Presentation] Cardiac-Specific Deletion of Suppressorof Cytokine Signaling-3 Prevents Doxoubicin-Induced Cardiomyopathy in Mice (2012)
  • Author(s): Kyogoku S, Yasukawa H, Nagata T, Oba T,Ohshima H, Minami T, Yajima T, Hoshijima M, Aoki H, Knowlton KU, Imaizumi T.
  • Organizer: The 85thScientific Sessions, Los Angels
  • Place of Presentation: USA
  • Year and Date: 20121103-1107
• [Presentation] Pioglitazone Decreases PlasmaFibroblast Growth Factor-21 Levels in Patients with Type 2 Diabetes (2012)
  • Author(s): Mawatari K, Tahara N, Yasukawa H, Oba T,Nagata T, Kyougoku S, Ohshima H, Minai T, Mizoguchi M, Sugi Y, Adachi H, Imaizumi T.
  • Organizer: The 85thScientific Sessions
  • Place of Presentation: Los Angels, USA
  • Year and Date: 20121103-1107
• [Presentation] Prevention of Doxorubicin-Induced Cardiomyopathy in Cardiac-Specific SOCS3 Deficient Mice by Preserving Energy Metabolism (2012)
  • Author(s): Kyogoku S, Yasukawa H, Nagata T, ObaT, Ohshima H, Minami T, Fukui D, Sugi Y,Aoki H, Imaizumi T
  • Organizer: 第29回国際心臓研究学会(ISHR)日本部会総会
  • Place of Presentation: 福岡
  • Year and Date: 20121026-1027
• [Presentation] Preventionof Doxorubicin-Induced Cardiomyopathy inCardiac-Specific SOCS3 Deficient Mice byAugmenting STAT3 Signaling Pathway (2012)
  • Author(s): 京極 幸子 安川 秀雄 、永田 隆信 、大場豊治 、大島英樹 、南知子、福井大介 、杉雄介 、青木浩樹 、今泉勉
  • Organizer: 第35回心筋代謝研究会
  • Place of Presentation: 東京
  • Year and Date: 20120707-0708
• [Presentation] ImpairedAngiogenesis During Hindlimb Ischemia inSkeletal Muscle-Specific STAT3 DeficientMice (2012)
  • Author(s): Ohshima H, Yasukawa H, Nagata T, KyogokuS, Oba T, Mawatari K, Futamata N, Minami T, Sugi Y, Sasaki K, Imaizumi T
  • Organizer: 第76回日本循環器学会
  • Place of Presentation: 福岡
  • Year and Date: 20120316-0318
• [Presentation] Activation of hypoxia inducible factor-erythropoietin pathway may prevent acute myocardial injury during remote ischemic preconditioning (2012)
  • Author(s): Oba T, Yasukawa H, Nagata T, KyougokuS, Futamata N, Mawatari K, Minami T, Sugi Y, Fukui D, Aoki H, Imaizumi T
  • Organizer: 第76回日本循環器学会
  • Place of Presentation: 福岡
  • Year and Date: 20120316-0318
• [Presentation] Prevention of Left Ventricular Remodeling after Acute Myocardial Infarction in Interleukin-17 Deficient Mice (2012)
  • Author(s): Minami T, Yasukawa H, Nagata T, Oba T,Kyogoku S, Ohshima H, Aoki H, Yoshimura A, Imaizumi T
  • Organizer: 第76回日本循環器学会
  • Place of Presentation: 福岡
  • Year and Date: 20120316-0318
• [Presentation] Pioglitazone Decreases PlasmaFibroblast Growth Factor-21 Levels inPatients with Type 2 Diabetes (2012)
  • Author(s): 馬渡 一寿、田原 宣広、安川 秀雄、大場 豊治、二又 誠義、永田 隆信、京極 幸子、大島 英樹、南 知子、溝口 ミノリ、足達 寿、今泉 勉;
  • Organizer: 第76回日本循環器学会
  • Place of Presentation: 福岡
  • Year and Date: 20120316-0318
• [Presentation] 腎神経を介した臓器連関による心筋保護機構 Remote ischemic preconditioningの臓器保護メカニズム- (2012)
  • Author(s): 安川 秀雄、大場 豊治、青木 浩樹、今泉勉
  • Organizer: 第16回日本心血管内分泌代謝学会
  • Place of Presentation: 東京
  • Year and Date: 2012-11-24
• [Presentation] 腎交感神経を介した臓器連関による心筋保護機構厚生労働省難治性疾患克服研究事業特発性心筋症に関する調査研究 (2012)
  • Author(s): 安川秀雄、大場豊治、永田隆信、京極幸子、大島英樹、南知子、青木浩樹、今泉勉
  • Organizer: 2011年度北風班報告会
  • Place of Presentation: 大阪
  • Year and Date: 2012-10-18
• [Presentation] サムスカの安全情報と使用経験 (2012)
  • Author(s): 安川秀雄、馬渡一寿、永田隆信、杉雄介、大場豊治、京極幸子、大島英樹、南知子、今泉勉
  • Organizer: 久留米心不全セミナー
  • Place of Presentation: 久留米
  • Year and Date: 2012-05-18