Preclinical study of cardiovascular regenerative medicine using asialoerythropoietin

2011 Fiscal Year Final Research Report

• Project/Area Number: 21590887
• 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: Niigata University
• Principal Investigator: TOBA Ken 新潟大学, 医歯学総合病院, 講師 (60313540)
• Co-Investigator(Kenkyū-buntansha): HANAWA Haruo 新潟大学, 医歯学系, 講師 (40282983) ; OZAWA Takuya 新潟大学, 医歯学総合病院, 特任助教 (70467075)
• Project Period (FY): 2009 – 2011
• Keywords: 臨床心血管病態学 / 心血管系再生医学

Research Abstract

There have been technical and ethical problems for the application of cell therapy. Alternative medical such as cytokines other than cultured cells may help resolvingtheseproblems. Asialresourcesoerythropoietin(AEPO), a natural derivative of EPO, plays important role in angiogenesis and tissue protection of cardiovascular and central nervous systems. We started the preclinical studies on the in vitro and in vivo effects of AEPO. AEPO exerted strong cardiovasculoprotective and angiogenic activity in vivo. EPO derivatives expressed in vitro angiogenic activity in an intrinsic IL-6 dependent manner. AEPO showed tissue affinity in vitro and in vivo. We have entered into negotiations with a partner company for clinical applications of AEPO.

Research Products

• [Journal Article] Erythropoietin, but not asialo-erythropoietin or carbamyl-erythropoietin, attenuates monocrotaline-induced pulmonary hypertension in rats (2012)
  • Author(s): Ikarashi N, Toba K, Kato K, Ozawa T, Oda M, Takayama T, Kobayashi H, Yanagawa T, Hanawa H, Suzuki T, Nakazawa M, Nomoto N, Asami F, Higuchi M, Saito H, Aizawa Y
  • Journal Title: Clinical and Experimental Hypertension Volume: (in press)
  • Peer Reviewed
• [Journal Article] Erythropoietin, progenitor cells and restenosis (2012)
  • Author(s): Minamino T, Toba K, Higo S, Nakatani D, Ozawa T
  • Journal Title: Thrombosis and Haemostasis Volume: (in press)
  • Peer Reviewed
• [Journal Article] Hypocellularity and insufficient expression of angiogenic factors in implanted autologous bone marrow in patients with chronic critical limb ischemia (2012)
  • Author(s): Oda M, Toba K, Kato K, Ozawa T, Yanagawa T, Ikarashi N, Takayama T, Suzuki T, Hanawa H, Masuko M, Kobayashi H, Aizawa Y
  • Journal Title: Heart and Vessels Volume: 27 Pages: 38-45
  • Peer Reviewed
• [Journal Article] Rise in international normalized ratio after a catastrophic earthquake in patients treated with warfarin (2011)
  • Author(s): Oda M, Watanabe H, Oda E, Tomita M, Obata H, Ozawa T, Oda Y, Iizuka T, Toba K, Aizawa Y
  • Journal Title: International Journal of Cardiology Volume: 52 Pages: 109-110
  • Peer Reviewed
• [Journal Article] シリーズ「日本発臨床研究の紹介と反省点を語る」: EPO/AMI-1研究 (2011)
  • Author(s): 鳥羽健, 加藤公則, 小澤拓也, 相澤義房
  • Journal Title: 日本内科学会雑誌 Volume: 100 Pages: 2008-2014
• [Journal Article] Free heme is a danger signal inducing expression of proinflammatory proteins in cultured cells derived from normal rat hearts (2011)
  • Author(s): Hao K, Hanawa H, Ding L, Ota Y, Yoshida K, Toba K, Ogura M, Ito H, Kodama M, Aizawa Y
  • Journal Title: Molecular Immunology Volume: 48 Pages: 1191-1202
  • Peer Reviewed
• [Journal Article] A novel program to accu-rately quantify infarction volume by(99m) Tc MIBI SPECT, and its application for re-analyzing the effect of erythropoietin admini-stration in patients with acute myocardial infarction (2010)
  • Author(s): Yoshimura N, Toba K, Ozawa T, Aizawa Y, Hosoya T
  • Journal Title: Circulation Journal Volume: 74 Pages: 2741-2743
  • Peer Reviewed
• [Journal Article] エリスロポエチンの急性心筋梗塞に対する臨床試験 (2010)
  • Author(s): 小澤拓也, 鳥羽健, 相澤義房
  • Journal Title: 循環器内科 Volume: 67 Pages: 232-236
• [Journal Article] Establishment of culturing system for ex-vivo expansion of angiogenic immature erythroid cells, and its application for treatment of patients with chronic severe lower limb ischemia (2010)
  • Author(s): Oda M, Toba K, Ozawa T, Kato K, Yanagawa T, Ikarashi N, Takayama T, Suzuki T, Hanawa H, Fuse I, Nakata K, Narita M, Takahashi M, Aizawa Y
  • Journal Title: Journal of Molecular and Cellular Cardiology Volume: 49 Pages: 347-353
  • Peer Reviewed
• [Journal Article] Expression of the peptide hormone hepcidin increases in cardiomyocytes under myocarditis and myocardial infarction (2010)
  • Author(s): Isoda M, Hanawa H, Watanabe R, Yoshida T, Toba K, Yoshida K, Kojima M, Otaki K, Hao K, Ding L, Tanaka K, Takayama T, Kato K, Okura Y, Kodama M, Ota Y, Hayashi J, Aizawa Y
  • Journal Title: The Journal of Nutritional Biochemistry Volume: 21 Pages: 749-756
  • Peer Reviewed
• [Journal Article] Single-dose intravenous administration of recombin-ant human erythropoietin is a promising treatment for patients with acute myocar-dial infarction-randomized controlled pilot trial of EPO/AMI-1 study- (2010)
  • Author(s): Ozawa T, Toba K, Suzuki H, Kato K, Iso Y, Akutsu Y, Kobayashi Y, Takeyama Y, Kobayashi N, Yoshimura N, Akazawa K, Aizawa Y
  • Journal Title: Circulation Journal Volume: 74 Pages: 1415-1423
  • Peer Reviewed
• [Journal Article] Lipocalin-2/neutrophil gelatinase-B associated lipocalin is strongly induced in hearts of rats with autoimmune myocarditis and in human myocarditis (2010)
  • Author(s): Ding L, Hanawa H, Ota Y, Hasegawa G, Hao K, Asami F, Watanabe R, Yoshida T, Toba K, Yoshida K, Ogura M, Kodama M, Aizawa Y
  • Journal Title: Circulation Journal Volume: 74 Pages: 523-530
  • Peer Reviewed
• [Journal Article] Serum hepcidin-20 is elevated during the acute phase of myocardial infarction (2009)
  • Author(s): Suzuki H, Toba K, Kato K, Ozawa T, Tomosugi N, Higuchi M, Kusuyama T, Iso Y, Kobayashi N, Yokoyama S, Fukuda N, Saitoh H, Akazawa K, Aizawa Y
  • Journal Title: Tohoku Journal of Experimental Medicine Volume: 218 Pages: 93-98
  • Peer Reviewed
• [Journal Article] エリスロポエチン誘導体の血管新生作用 (2009)
  • Author(s): 鳥羽健, 小澤拓也, 相澤義房
  • Journal Title: Angiology Frontier Volume: 8 Pages: 61-69
• [Journal Article] エリスロポエチンの心・血管系疾患への応用 (2009)
  • Author(s): 鳥羽健, 加藤公則
  • Journal Title: 循環器科 Volume: 66 Pages: 424-432
• [Presentation] Long-term effects of EVEETA therapy in patients with severe peripheral artery disease (2011)
  • Author(s): Oda M, Ozawa T, Toba K, Kto K, Takayama T, Yanagawa T, Ikarashi N, Suzuki T, Hanawa H, Aizawa Y
  • Organizer: 第75回日本循環器学会総会学術集会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2011-08-03
• [Presentation] ヘパリン結合性エリスロポエチンの作成とその生物学的特徴の検討 (2010)
  • Author(s): 森山雅人,鳥羽健,塙晴雄,樋口正人,齊藤英樹,相澤義房
  • Organizer: 第72回日本血液学会学術集会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2010-09-24
• [Presentation] 特別企画「循環器Translational Researchの課題」-3.心筋梗塞に対するエリスロポエチン治療(指定演題) (2010)
  • Author(s): 鳥羽健、小澤拓也、相澤義房
  • Organizer: 第58回日本心臓病学会学術集会
  • Place of Presentation: 東京国際フォーラム
  • Year and Date: 2010-09-17
• [Presentation] Establishment of a novel synthetic derivative of human erythropoietin designed to bind to glycosaminoglycans (2010)
  • Author(s): Moriyama M, Toba K, Hanawa H, Higuchi M, Saitoh H, Aizawa Y
  • Organizer: JSH International Symposium 2010
  • Place of Presentation: 秋田大学
  • Year and Date: 2010-07-16
• [Presentation] Free heme strongly induces pro-inflammatory proteins in cultured cells derived from normal rat hearts (2010)
  • Author(s): Hao K, Hanawa H, Ding L, Toba K, Watanabe R, Yoshida T, Kodama M, Aizawa Y
  • Organizer: 第74回日本循環器学会総会学術集会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2010-03-06
• [Presentation] The angiogenic effects of erythropoietin-derivatives (2010)
  • Author(s): Yanagawa T, Toba K, Takayama T, Oda M, Otaki K, Ikarashi N, Minagawa S, Ozawa T, Hanawa H, Aizawa Y
  • Organizer: 第74回日本循環器学会総会学術集会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2010-03-06
• [Presentation] Single-dose intravenous-administration of erythropoietin improved cardiac function in patients with acute myocardial infarction (2010)
  • Author(s): Ozawa T, Toba K, Suzuki H, Kato K, Minamino T, Iso Y, Akutsu Y, Kobayashi Y, Takayama Y, Konayashi N, Yoshimura N, Komuro I, Aizawa Y
  • Organizer: 第74回日本循環器学会総会学術集会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2010-03-06
• [Presentation] Single-dose intravenous-administration of recombinant human erythropoietin considerably improved cardiac function in patients with acute myocardial infarction : A randomized controlled pilot trial of EPO/AMI-I study (2009)
  • Author(s): Ozawa T, Toba K, Suzuki H, Kato K, Iso Y, Akutsu Y, Kobayashi Y, Takayama Y, Kobayashi N, Yoshimura N, Akazawa K, Aizawa Y
  • Organizer: AHA Scientific Sessions 2009
  • Place of Presentation: Orlando World Center Marriott Orlando
  • Year and Date: 2009-11-14
• [Presentation] 重症下肢虚血患者に対する体外増幅自己赤芽球移植を用いた血管再生治療の第I/II相臨床試験 (2009)
  • Author(s): 小澤拓也,鳥羽健,加藤公則,小田雅人,柳川貴央,五十嵐登,高山亜美,塙晴雄,相澤義房
  • Organizer: 第57回日本心臓病学会学術集会
  • Place of Presentation: ロイトン札幌
  • Year and Date: 2009-09-19
• [Presentation] 急性心筋梗塞に対するエリスロポエチン投与による心機能改善効果 (2009)
  • Author(s): 小澤拓也,鳥羽健,加藤公則,柳川貴央,高山亜美,相澤義房,鈴木洋,磯良崇,小林直彦,横山慎一郎,福田昇
  • Organizer: 第57回日本心臓病学会学術集会
  • Place of Presentation: ロイトン札幌
  • Year and Date: 2009-09-19
• [Presentation] 重症下肢虚血患者に対する体外増幅自己赤芽球移植を用いた血管再生治療の第I/II相臨床試験 (2009)
  • Author(s): 小澤拓也,鳥羽健,加藤公則,小田雅人,柳川貴央,五十嵐登,高山亜美,塙晴雄,相澤義房
  • Organizer: 第106回日本内科学会総会
  • Place of Presentation: 東京国際フォーラム
  • Year and Date: 2009-04-09
• [Book] 冠動脈疾患(上)-診断と治療の進歩-, 2.心筋再生療法, 3)エリスロポエチンを用いた心血管疾患の治療 (2011)
  • Author(s): 鳥羽健,小澤拓也,加藤公則
  • Total Pages: 533-536
  • Publisher: 日本臨床社
• [Book] 循環器再生医学の現状と展望, Chapter 2血管新生療法の基礎研究 (2011)
  • Author(s): 鳥羽健
  • Total Pages: 45-54
  • Publisher: メディカルレビュー社
• [Remarks]
  • URL: http://www.med.niigata-u.ac.jp/in1/godoproject/saisei.html