Molecular mechanisms of suppression of macrophage foam cell formation by an erythropoietin receptor agonist

• Project/Area Number: 23591108
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Jichi Medical University
• Principal Investigator: UEBA HIROTO 自治医科大学, 医学部, 講師 (80316546)
• Co-Investigator(Kenkyū-buntansha): KAWAKAMI Masanobu 自治医科大学, 医学部, 名誉教授 (40161286)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 動脈硬化 / erythropoietin / マクロファージ / シグナル伝達

Research Abstract

Erythropoietin (EPO) has been shown to have nonerythropoietic, tissue-protective effects although prothrombotic effects of EPO hamper its clinical use. Recently, we demonstrated that an EPO receptor agonist (HBSP) that does not have prothrombotic effects suppresses coronary atherosclerosis in Watanabe heritable hyperlipidemic spontaneous myocardial infarction (WHHLMI) rabbits. In the present study, we examined the effects of pyroglutamate HBSP (ARA290) on macrophage foam cell formation. ARA290 significantly inhibited it by up-regulating the expression of ABCA1 that plays a pivotal role in reverse cholesterol transport and reduced aortic plaque area in apo E deficient mice. Because ARA290 is chemically more stable than HBSP, it may be a promising drug for treating atherosclerosis.

Research Products

• [Journal Article] Suppression of coronary atherosclerosis by a helix B surface peptide, a nonerythropoietic tissue- protective compound derived from erythropoietin (2013)
  • Author(s): Ueba H, Shiomi M, Brines M, Yamin M, Kobayashi T, Ako J, Momomura S, Cerami A, Kawakami M.
  • Journal Title: Mol Med. Volume: 19(1) Pages: 195-202
• [Journal Article] Suppression of coronary atherosclerosis by helix B surface peptide, a nonerythropoietic, tissue-protective compound derived from erythropoietin. (2013)
  • Author(s): Ueba H, Shiomi M, Brines M, Yamin M, Kobayashi T, Ako J, Momomura SI, Cerami A, Kawakami M
  • Journal Title: Molecular Medicine Volume: 19 Issue: 1 Pages: 195-202
  • DOI: 10.2119/molmed.2013.00037
  • Peer Reviewed
• [Journal Article] Reply to Abdelwahid and Smith : The effect on cardiomyocytes of helix B-surface peptide (HBSP), a peptide with cell-protective but not erythro- poietic activities of erythropoietin (2011)
  • Author(s): Masanobu Kawakami, Hiroto Ueba, Michael Brines, Michael Yamin, Tomio Umemoto, Junya Ako, Shin-ichi Momomura, and Anthony Cerami
  • Journal Title: Proc Natl Acad Sci U S A Volume: 108(6)
• [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): Kawakami M, Ueba H, Brines M, Yamin M, Umemoto T, Ako J, Momomura S, and Cerami A
  • Journal Title: Proc Natl Acad Sci U S A Volume: 108(6) Issue: 6
  • DOI: 10.1073/pnas.1012530108
  • Peer Reviewed
• [Journal Article] Effects of Thiazolidinediones on In- Stent Restenosis : A Review of IVUS Studies
  • Author(s): Yasu T, Ueba H, Katayama T, Kawakami M.
  • Journal Title: Intravascular Ultrasound, Yasuhiro Honda (Ed.) Volume: (ISBN :978-953-307-900-4)(InTech 2012)
  • URL: http://www.intechopen.com/books/intravascular-ultrasound/effects-of-thiazolidinedione-on-in-stent-restenosis-a-review-of-ivus-studies
• [Presentation] Helix B surface peptide, a nonerythropoietic erythropoietin derivative, modifies macrophage polarization and prevents progression of coronary atherosclerotic lesions (2014)
  • Author(s): Ueba, H., Shiomi, M., Brines, M., Yamin M., Cerami, A., Momomura, S.
  • Organizer: The 78th Annual Scientific Meeting of the Japanese Circulation Society
  • Place of Presentation: Tokyo
  • Year and Date: 2014-03-22
• [Presentation] 慢性心不全動物モデルにおける非造血性エリスロポエチン誘導体による心筋保護作用―抗アポトーシス効果による適応 (2013)
  • Author(s): 上羽洋人, Michael Brines, Michael Yamin, Anthony Cerami,梅本富士,阿古潤哉,川上正舒,百村伸一
  • Organizer: 第17回日本適応医学会学術集会
  • Place of Presentation: さいたま市
  • Year and Date: 2013-06-29
• [Presentation] Suppression of coronary atherosclerosis by a helix B surface peptide, a nonerythropoietic tissue- protective compound derived from erythro- poietin (2013)
  • Author(s): Ueba, H., Shiomi, M., Brines, M., Yamin, M., Ako, J., Momomura, S., Cerami, A., Kawakami, M.
  • Organizer: The 77th Annual Scientific Meeting of the Japanese Circulation Society
  • Place of Presentation: Yokohama
  • Year and Date: 2013-03-15
• [Presentation] Suppression of coronary atherosclerosis by a helix B surface peptide, a nonerythropoietic tissue-protective compound derived from erythropoietin (2013)
  • Author(s): Ueba, H., Shiomi, M., Brines, M., Yamin, M., Ako, J., Momomura, S., Cerami, A., Kawakami
  • Organizer: The 77th Annual Scientific Meeting of the Japanese Circulation Society
  • Place of Presentation: 横浜市
• [Presentation] Cardioprotective Prop- erties of Helix B Surface Peptide, a Nonerythropoietic Derivative Mimicking the 3D Structure of Erythropoietin (2011)
  • Author(s): Ueba, H., Brines, M., Yamin, M., Umemoto, T., Ako, J., Momomura, S., Cerami, A., Kawakami, M.
  • Organizer: The 75th Annual Scientific Meeting of the Japanese Circulation Society
  • Place of Presentation: Yokohama
  • Year and Date: 2011-08-03
• [Presentation] Cardioprotective Properties of Helix B Surface Peptide, a Nonerythropoietic Derivative Mimicking the 3D Structure of Erythropoietin (2011)
  • Author(s): Ueba, H., Brines, M., Yamin, M., Umemoto, T., Ako, J., Momomura, S., Cerami, A., Kawakami, M.
  • Organizer: The 75th Annual Scientific Meeting of the Japanese Circulation Society
  • Place of Presentation: Yokohama