Development of a novel treatment strategy that targets erythropoietin receptors and HIF

• Project/Area Number: 22590800
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Tohoku University
• Principal Investigator: KAGAYA Yutaka 東北大学, 大学院・医学系研究科, 教授 (90250779)
• Co-Investigator(Kenkyū-buntansha): 武田 守彦 東北大学, 病院, 助教 (30375084)
• Co-Investigator(Renkei-kenkyūsha): TAKEDA Morihiko 東北大学, 病院, 助教 (30375084)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2010: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 心不全 / 心肥大 / エリスロポエチン / HIF / プロリル水酸化酵素 / 左室肥大 / 心筋保護 / 圧負荷

Research Abstract

Our objective was to determine whether novel strategies to treat heart failure with recombinant human erythropoietin (EPO) and a prolyl hydroxylase (PHD) inhibitor that stabilizes hypoxia-inducible factor (HIF) are useful. EPO protected the pressure-overload induced hypertrophied left ventricle in mice by maintaining left ventricular systolic function and improved the survival. The PHD inhibitor failed to demonstrate such a protective effect at least with the doses and treatment period usedin the present study. Further investigations are required to address the issue.

Research Products

• [Journal Article] Current Perspectives on Protective Roles of Erythropoietin in Cardiovascular System: Erythropoietin Receptor as a Novel Therapeutic Target (2012)
  • Author(s): Kagaya Y, Asaumi Y, Wang W, Takeda M, Nakano M, Satoh K, Fukumoto Y, Shimokawa H.
  • Journal Title: The Tohoku Journal of Experimental Medicine Volume: 227 Issue: 2 Pages: 83-91
  • DOI: 10.1620/tjem.227.83
  • NAID: 10030779568
  • ISSN: 0040-8727, 1349-3329
  • Peer Reviewed
• [Journal Article] Emergence of the erythropoietin/erythropoietin receptor system as a novel cardiovascular target (Review). (2012)
  • Author(s): Kimio Satoh
  • Journal Title: J Cardiovasc Pharmacol. Volume: 58 Issue: 6 Pages: 570-574
  • DOI: 10.1097/fjc.0b013e318235e7bb
  • Peer Reviewed
• [Journal Article] Protective Effects of Recombinant Human Erythropoietin against Pressure Overload-Induced Left Ventricular Remodeling and Premature Death in Mice (2011)
  • Author(s): Wang W, Kagaya Y, Asaumi Y, Fukui S, Takeda M, Shimokawa H.
  • Journal Title: The Tohoku Journal of Experimental Medicine Volume: 225 Issue: 2 Pages: 131-143
  • DOI: 10.1620/tjem.225.131
  • NAID: 130004459935
  • ISSN: 0040-8727, 1349-3329
  • Peer Reviewed
• [Journal Article] Emergence of the erythropoietin/erythropoietin receptor system as anovel cardiovascular therapeutic target (2011)
  • Author(s): Satoh K, et. al.
  • Journal Title: J Cardiovasc Pharmacol Volume: in press
  • Peer Reviewed
• [Journal Article] OX40 ligand plays an important role in the development of atherosclerosis through vasa vasorum neovascularization (2010)
  • Author(s): Nakano M, Fukumoto Y, Satoh K, Ito Y, Kagaya Y, Ishii N, Sugamura K, Shimokawa H.
  • Journal Title: Cardiovasc Res. Volume: 88 Issue: 3 Pages: 539-46
  • DOI: 10.1093/cvr/cvq211
  • Peer Reviewed
• [Journal Article] Thyroid hormone and chronically unloaded hearts (2010)
  • Author(s): Ito K, Kagaya Y, Shimokawa H.
  • Journal Title: Vascul Pharmacol Volume: 52 Issue: 3-4 Pages: 138-41
  • DOI: 10.1016/j.vph.2009.10.004
  • Peer Reviewed
• [Journal Article] OX40 ligand plays an important role in the development of atherosclerosis through vasa vasorum neovascularization. (2010)
  • Author(s): Nakano M, et. al.
  • Journal Title: Cardiovasc Res Volume: 88(in press) Pages: 539-546
  • Peer Reviewed
• [Presentation] Prognostic impact of enhanced F18-fluorodeoxyglucose accumulation in the right ventricle in patients with pulmonary hypertension (2013)
  • Author(s): Tatebe S, Fukumoto Y, Sugimura K, Miura Y, Nochioka K, Aoki T, Yamamoto S, Wakayama M, Kagaya Y, Shimokawa H.
  • Organizer: 第77回日本循環器学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2013-03-17
• [Presentation] Prognostic impact of enhanced [F-18]fluorodeoxyglucose accumulation in the right ventricle in patients with pulmonary hypertension (2013)
  • Author(s): Tatebe S, Fukumoto Y, Sugimura K, Miura Y, Nochioka K, Aoki T, Yamamoto S, Wakayama M, Kagaya Y, Shimokawa H
  • Organizer: 第77回日本循環器学会学術集会
  • Place of Presentation: 横浜
• [Presentation] Prognostic significance of enhanced [^<18>F] fluorodeoxyglucose accumulation in the right ventricular free wall in patients with pulmonary hypertension (2012)
  • Author(s): Tatebe S, Fukumoto Y, Sugimura K, Satoh K, Miura Y, Nochioka K, Aoki T, Yamamoto S, Wakayama-Oikawa M, Kagaya Y, Shimokawa H.
  • Organizer: Scientific Sessions of American Heart Association 2012
  • Place of Presentation: Los Angeles, U.S.A.
  • Year and Date: 2012-11-05
• [Presentation] Prognostic significance of enhanced [18F] fluorodeoxyglucose accumulation in the right ventricular free wall in patients with pulmonary hypertension (2012)
  • Author(s): Tatebe S, Fukumoto Y, Sugimura K, Satoh K, Miura Y, Nochioka K, Aoki T, Yamamoto S, Wakayama-Oikawa M, Kagaya Y, Shimokawa H.
  • Organizer: Scientific Sessions of American Heart Association 2012
  • Place of Presentation: Los Angels, U.S.A.
• [Presentation] 心不全と貧血 (2011)
  • Author(s): 加賀谷豊
  • Organizer: 第48回日本臨床生理学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2011-11-05
• [Presentation] 心筋血流シンチの基礎とエビデンス (2011)
  • Author(s): 加賀谷豊
  • Organizer: 福島地区日本心臓核医学会地域別教育研修会
  • Place of Presentation: 郡山
  • Year and Date: 2011-11-04
• [Presentation] 心不全と貧血 (2011)
  • Author(s): 加賀谷豊
  • Organizer: 第48回日本臨床生理学会学術集会
  • Place of Presentation: 東京都(招待講演)
  • Year and Date: 2011-11-04
• [Presentation] エリスロポエチン受容体と循環器疾患 (2011)
  • Author(s): 加賀谷豊
  • Organizer: 第29回内分泌代謝学サマーセミナー
  • Place of Presentation: 仙台
  • Year and Date: 2011-07-08
• [Presentation] エリスロポエチン受容体と循環器疾患 (2011)
  • Author(s): 加賀谷豊
  • Organizer: 第29回内分泌代謝学サマーセミナー
  • Place of Presentation: 仙台市(招待講演)
  • Year and Date: 2011-07-08
• [Presentation] エリスロポエチンと心臓 (2011)
  • Author(s): 加賀谷豊
  • Organizer: 仙台白百合女子大学平成23年度健康栄養特別講義
  • Place of Presentation: 仙台
  • Year and Date: 2011-05-14
• [Presentation] Recombinant human erythropoietin protects the heart from pressure overload-mduced left ventricular dysfunction in mice in vivo (2010)
  • Author(s): Wang W, et. al.
  • Organizer: 20th Word Congress of the International Societyfor Heart Reseatch
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2010-05-14
• [Book] エリスロポエチンの心保護作用.循環器臨床サピア7:CKDと心血管病を理解する(筒井裕之編) (2010)
  • Author(s): 加賀谷豊
  • Publisher: 中山書店(東京)
• [Book] 循環器臨床サピア7 : CKDと心血管病を理解する(エリスロポエチンの心保護作用) (2010)
  • Author(s): 加賀谷豊(筒井裕之編)
  • Total Pages: 280
  • Publisher: 中山書店