Anti-atherosclerotic effects of an erythropoietin receptor agonist

2010 Fiscal Year Final Research Report

• Project/Area Number: 20590887
• 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: Jichi Medical University
• Principal Investigator: UEBA Hiroto Jichi Medical University, 医学部, 講師 (80316546)
• Co-Investigator(Kenkyū-buntansha): KAWAKAMI Masanobu 自治医科大学, 医学部, 教授 (40161286)
• Project Period (FY): 2008 – 2010
• Keywords: エリスロポエチン / アゴニスト / 動脈硬化 / 血管内皮細胞 / アポトーシス / シグナル伝達 / WHHLMIウサギ

Research Abstract

Erythropoietin (EPO) has been shown to have nonhematopoietic, tissue-protective effects, including suppression of atherosclerosis. However, prothrombotic effects of EPO hinder its clinical use in non-anemic patients. In the present study, we examined anti-atherosclerotic effects of an EPO receptor agonist (EPORA) that does not have adverse effects of EPO using myocardial infarction?prone Watanabe heritable hyperlipidemic (WHHLMI) rabbits. EPORA demonstrated anti-apoptotic and anti-inflammatory effects and significantly suppressed the progression of coronary atherosclerotic lesions in WHHLMI rabbits. Because EPORA has pleiotropic effects just like statins, it may be a promising candidate for a novel anti-atherosclerotic agent.

Research Products

• [Journal Article] Reply to Abdelwahid and Smith : The effect on cardiomyocytes of helix B-surface peptide (HBSP), a peptide with cell-protective but not erythropoietic activities of erythropoietin. (2011)
  • Author(s): Masanobu Kawakami, Hiroto Ueba, Michael Brines, Michael Yamin, Tomio Umemoto, Junya Ako, Shin-ichi Momomura, Anthony Cerami
  • Journal Title: Proc Natl Acad Sci USA. 108(6) Pages: E18
• [Journal Article] Cardioprotection by a nonerythropoietic, tissue-protective peptide mimicking the 3D structure of erythropoietin. (2010)
  • Author(s): Hiroto Ueba, Michael Brines, Michael Yamin, Tomio Umemoto, Junya Ako, Shin-ichi Momomura, Anthony Cerami, Masanobu Kawakami
  • Journal Title: Proc Natl Acad Sci USA. 107(32) Pages: 14357-14362
• [Journal Article] C-Reactive protein induces endothelial cell apoptosis and matrix metalloproteinase-9 production in human mononuclear cells : Implications for the destabilization of atherosclerotic plaque. (2008)
  • Author(s): Aoi Nabata, Masatoshi Kuroki, Hiroto Ueba, Shigemasa Hashimoto, Tomio Umemoto, Hiroshi Wada, Takanori Yasu, Muneyasu Saito, Shin-ichi Momomura, Masanobu Kawakami
  • Journal Title: Atherosclerosis 196(1) Pages: 129-135
• [Presentation] Role of osteopontin and αvβ3 integrin in the regulation of endothelial cell survival by endothelial cell-monocyte interaction. (2010)
  • Author(s): Ueba, H, Hashimoto, S, Umemoto, T, Ako, J, Momomura, S, Kawakami, M.
  • Organizer: 第42回日本動脈硬化学会総会
  • Place of Presentation: 岐阜市
  • Year and Date: 2010-07-15
• [Presentation] Cardiomyocyte protection by a nonerythropoietic, tissue-protective peptide derived from erythropoietin. (2010)
  • Author(s): Ueba, H, Brines, M, Yamin, M, Umemoto, T, Ako, J, Momomura, S, Cerami, A, Kawakami, M.
  • Organizer: 第74回日本循環器学会総会
  • Place of Presentation: 京都市
  • Year and Date: 2010-03-05
• [Presentation] Induction of endothelial cell apoptosis and monocyte matrix metalloproteinase-9 production by C-reactive protein. (2009)
  • Author(s): Ueba, H, Nabata, A, Kuroki, M, Hashimoto, S, Umemoto, T, Sugawara, Y, Kubo, N, Momomura, S, Kawakami, M.
  • Organizer: 第73回日本循環器学会総会
  • Place of Presentation: 大阪市
  • Year and Date: 2009-03-21