The role of inflammation and oxydative stress in the development of anemia in chronic heart failure

• Project/Area Number: 15K09148
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Hyogo University of Health Sciences
• Principal Investigator: Tsujino Takeshi 兵庫医療大学, 薬学部, 教授 (90283887)
• Co-Investigator(Kenkyū-buntansha): 内藤 由朗 兵庫医科大学, 医学部, 講師 (10446049) ; 増山 理 兵庫医科大学, 医学部, 教授 (70273670)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 慢性心不全 / 貧血 / 心腎貧血症候群 / インドキシル硫酸 / エリスロポエチン / 鉄 / 好中球リンパ球比 / 炎症

Outline of Final Research Achievements

To elucidate the mechanisms of development of anemia and leukocyte abnormality in chronic heart failure, we performed animal experiments using Dahl salt-sensitive (DS) rats, in which high-salt diet induces hypertension, heart failure, anemia, and an increase in neutrophil/lymphocyte ratio (NLR). We found shortened half-life of red blood cell is the main cause of anemia in DS rats, and free hemoglobin released from red blood cell might cause renal damage. We also performed animal experiments using adenine-induced nephropathy model of mouse. We found elevated serum indoxyl sulfate induces increase in NLR by distortion of leukocyte hematopoiesis in bone marrow.

Research Products

• [Journal Article] Altered expression of intestinal duodenal cytochrome b and divalent metal transporter 1 might be associated with cardio-renal anemia syndrome (2017)
  • Author(s): Naito Y, Sawada H, Oboshi M, Okuno K, Yasumura S, Okuhara Y, Eguchi A, Nishimura K, Soyama Y, Asakura M, Ishihara M, Tsujino T, Masuyama T
  • Journal Title: Heart and Vessels Volume: 32 Issue: 11 Pages: 1410-1414
  • DOI: 10.1007/s00380-017-1013-4
  • Peer Reviewed
• [Journal Article] Attenuation of hypertension and renal damage in renovascular hypertensive rats by iron restriction. (2016)
  • Author(s): Oboshi M, Naito Y, Sawada H, Iwasaku T, Okuhara Y, Eguchi A, Hirotani S, Mano T, Tsujino T, Masuyama T.
  • Journal Title: Hypertens Res Volume: 39 Issue: 12 Pages: 832-839
  • DOI: 10.1038/hr.2016.93
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] 球形吸着炭(AST-120)は、慢性腎臓病による好中球/リンパ球比の増加を抑制する (2018)
  • Author(s): 伊藤 都裕, 辻野 健
  • Organizer: 日本薬学会第138年会
• [Presentation] Reduced half-life of erythrocytes in Dahl/Salt sensitive rats is the cause of the renal proximal tubule damage (2017)
  • Author(s): Eri Manabe, Satoyasu Ito, Takeshi Tsujino, Tohru Masuyama
  • Organizer: 第81回日本循環器学会学術集会
  • Place of Presentation: 石川県立音楽堂（石川県・金沢市）
  • Year and Date: 2017-03-19
• [Presentation] Intestinal iron transporters in cardio-renal anemia syndrome (2017)
  • Author(s): Yasumura Seiki, Naito Yoshiro, Oboshi Makiko, Okuno Keisuke, Okuhara Yoshitaka, Ando Tomotaka, Nishimura Koichi, Orihara Yoshiyuki, Asakura Masanori, Masuyama Tohru.
  • Organizer: 第21回日本心不全学会学術集会
• [Presentation] 腎線維化病変における鉄の関与 (2017)
  • Author(s): 康村誠希、内藤由朗、奥野圭佑、大星真貴子、辻野 健、増山 理.
  • Organizer: 第40回日本高血圧学会総会
• [Presentation] 慢性腎臓病は白血球分画異常を引き起こす (2017)
  • Author(s): 伊藤 都裕、坂本 淳一、高本 光次郎、真鍋 恵理、増山 理、辻野 健
  • Organizer: 第67回日本薬学会近畿支部総会・大会
• [Presentation] 慢性心不全モデルラットの貧血の原因は赤血球半減期の短縮である (2016)
  • Author(s): 真鍋恵理、佐々木尚子、大野喜也、田中稔之、伊藤都裕、増山理、辻野 健
  • Organizer: 第20回日本心不全学会学術集会
  • Place of Presentation: ロイトン札幌（北海道・札幌市）
  • Year and Date: 2016-10-07
• [Presentation] 高血圧患者における食事性鉄制限の有用性の検討. (2016)
  • Author(s): 内藤 由朗, 大星 真貴子, 澤田 悠, 辻野 健, 増山 理.
  • Organizer: 第39回日本高血圧学会総会
  • Place of Presentation: 仙台国際センター（宮城県・仙台市）
  • Year and Date: 2016-09-30