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Research for prevention of complications in cardiovascular surgeries through regulating HMGB1

Research Project

Project/Area Number 16K10625
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Cardiovascular surgery
Research InstitutionKyoto University

Principal Investigator

Uehara Kyokun  京都大学, 医学研究科, 客員研究員 (60462280)

Co-Investigator(Kenkyū-buntansha) 池田 義  京都大学, 医学研究科, 准教授 (40281092)
山崎 和裕  京都大学, 医学研究科, 講師 (50464227)
南方 謙二  京都大学, 医学研究科, 講師 (60539675)
升本 英利  京都大学, 医学研究科, 助教 (70645754)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords弁膜疾患外科学 / 人工心肺 / 全身性炎症反応症候群
Outline of Final Research Achievements

The administration of human recombinant thrombomodulin (TM) on a rat cardiopulmonary bypass model attenuated blood HMGB1 and lung tissue mRNA level of inflammatory cytokines and HMGB1, as well as histological lung injury and cytoplasmic expression of HMGB1. The administration of anti-inflammatory TM domain without activity of anti-coagulation on a rat cardiopulmonary bypass model showed the attenuation of blood HMGB1 level without prolonged activated coagulation time. Anti-inflammatory domain of TM would be potentially a new effective strategy on prevention of inflammatory complications related to cardiovascular surgeries through the regulation of HMGB1.

Academic Significance and Societal Importance of the Research Achievements

心臓血管外科手術において、炎症反応に関わる合併症の発症は致死的である。そういった重篤な病態における標的として現在着目されているのがHMGB1であり、その活性抑制は現在特に注目されている治療法である。本研究成果は致命的な心臓血管外科術後合併症に対する新治療法の開発につながり、学術的および社会的意義に富むものであると思われる。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (23 results)

All 2019 2018 2017 2016 Other

All Journal Article (8 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 8 results,  Open Access: 2 results) Presentation (14 results) (of which Int'l Joint Research: 6 results) Remarks (1 results)

  • [Journal Article] MicroRNA-145-loaded poly(lactic-co-glycolic acid) nanoparticles attenuate venous intimal hyperplasia in a rabbit model.2019

    • Author(s)
      Nishio H, Masumoto H, Sakamoto K, Yamazaki K, Ikeda T, Minatoya K.
    • Journal Title

      J Thorac Cardiovasc Surg

      Volume: In press Issue: 6 Pages: 2242-2251

    • DOI

      10.1016/j.jtcvs.2018.08.115

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] On-pump beating CABG concomitant with bilateral living-donor lobar lung transplantation.2019

    • Author(s)
      Ueyama K, Miyahara S, Ide Y, Sakamoto K, Kanemitsu H, Yamazaki K, Ikeda T, Aoyama A, Date H, Minatoya K.
    • Journal Title

      Heart Lung

      Volume: 48 Issue: 2 Pages: 166-168

    • DOI

      10.1016/j.hrtlng.2018.08.008

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Human iPS cell-derived cardiac tissue sheets for functional restoration of infarcted porcine hearts.2018

    • Author(s)
      Ishigami M, Masumoto H, Ikuno T, Aoki T, Kawatou M, Minakata K, Ikeda T, Sakata R, Yamashita JK, Minatoya K.
    • Journal Title

      PLoS One.

      Volume: 13 Issue: 8 Pages: e0201650-e0201650

    • DOI

      10.1371/journal.pone.0201650

    • NAID

      120006552912

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sustained release of basic fibroblast growth factor using gelatin hydrogel improved left ventricular function through the alteration of collagen subtype in a rat chronic myocardial infarction model.2018

    • Author(s)
      Li Z, Masumoto H, Jo JI, Yamazaki K, Ikeda T, Tabata Y, Minatoya K.
    • Journal Title

      Gen Thorac Cardiovasc Surg.

      Volume: 66 Issue: 11 Pages: 641-647

    • DOI

      10.1007/s11748-018-0969-z

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A therapeutic angiogenesis of sustained release of basic fibroblast growth factor using biodegradable gelatin hydrogel sheets in a canine chronic myocardial infarction model.2018

    • Author(s)
      Kumagai M, Minakata K, Masumoto H, Yamamoto M, Yonezawa A, Ikeda T, Uehara K, Yamazaki K, Ikeda T, Matsubara K, Yokode M, Shimizu A, Tabata Y, Sakata R, Minatoya K.
    • Journal Title

      Heart Vessels

      Volume: 33 Issue: 10 Pages: 1251-1257

    • DOI

      10.1007/s00380-018-1185-6

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A Recovery Cardiopulmonary Bypass Model Without Transfusion or Inotropic Agents in Rats.2018

    • Author(s)
      Hirao S, Masumoto H, Itonaga T, Minatoya K.
    • Journal Title

      J Vis Exp

      Volume: ー Issue: 133 Pages: 133-133

    • DOI

      10.3791/56986

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Recombinant human soluble thrombomodulin prevents acute lung injury in a rat cardiopulmonary bypass model.2017

    • Author(s)
      Hirao S, Minakata K, Masumoto H, Yamazaki K, Ikeda T, Minatoya K, Sakata R.
    • Journal Title

      J Thorac Cardiovasc Surg.

      Volume: 154 Issue: 6 Pages: 1973-1983

    • DOI

      10.1016/j.jtcvs.2017.05.051

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Tricuspid valve repair for severe tricuspid regurgitation due to pacemaker leads.2016

    • Author(s)
      Uehara K, Minakata K, Watanabe K, Sakaguchi H, Yamazaki K, Ikeda T, Sakata R.
    • Journal Title

      Asian Cardiovascular Thoracic Annalus

      Volume: 6 Issue: 6 Pages: 541-545

    • DOI

      10.1177/0218492316654775

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 大動脈弁輪拡張症に対する手術手技の工夫 2種類のバルサルバグラフトを用いたReimplantation法による自己弁温存基部再建術2018

    • Author(s)
      山﨑 和裕,上田 遼馬,竹原 眞人,坂本 和久,井出 雄二郎,金光 ひでお,南方 謙二,植山 浩二,池田 義,湊谷 謙司.
    • Organizer
      第46回日本血管外科学会学術総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] マウス下肢虚血モデルにおけるゼラチンスポンジを用いたiPS細胞由来血管構成細胞移植による血流改善および血管再生効果の検討2018

    • Author(s)
      津丸 真一,升本 英利,川東 正英,幾野 毅,金光 ひでお,植山 浩二,山﨑 和裕,池田 義,湊谷 謙司
    • Organizer
      第46回日本血管外科学会学術総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 当科におけるRCA#3に対する冠動脈バイパス術の成績2018

    • Author(s)
      山﨑 和裕,金光 ひでお,坂本 和久,井出 雄二郎,工藤 雅文,竹原 眞人,上田 遼馬,植山 浩二,池田 義,湊谷 謙司
    • Organizer
      第23回日本冠動脈外科学会学術大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ラット皮下移植実験による人工血管生体組織適合性についての検討2018

    • Author(s)
      藤原 靖恵,平尾 慎吾,川東 正英,升本 英利,金光 ひでお,山﨑 和裕,池田 義,湊谷 謙司
    • Organizer
      第71回日本胸部外科学会定期学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] MicroRNA-145封入ポリ乳酸グリコール酸共重合体ナノ粒子による静脈グラフト内膜肥厚抑制に関するウサギ頸動脈モデルを用いた検討2018

    • Author(s)
      西尾 博臣,升本 英利,川東 正英,坂本 和久,金光 ひでお,山﨑 和裕,池田 義,湊谷 謙司.
    • Organizer
      第71回日本胸部外科学会定期学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Transduction of micro RNA-145 using poly lactic-co-glycolic acid nanoparticles attenuates venous intimal hyperplasia in a rabbit vein graft disease model2018

    • Author(s)
      Nishio H, Masumoto H, Yamazaki K, Ikeda T, Minatoya K
    • Organizer
      ESC Congress 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Human iPS Cell-Derived Cardiac Tissue Transplantation to a Rat Unloaded Ischemic Heart Model Mimicking Left Ventricular Assist Device Implantation2018

    • Author(s)
      Heima D, Masumoto H, Kawatou M, Osada H, Ikeda T, Tabata Y, Minatoya K, Yamashita J.K.
    • Organizer
      AHA American Heart Association 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 慢性B型解離に対する超低体温循環停止、SIRC(Straight incision with rib-cross)アプローチによる胸部下行、胸腹部大動脈置換術2017

    • Author(s)
      坂本 和久,山﨑 和裕,上田 遼馬,竹原 眞人,矢次 遥,中津 太郎,井出 雄二郎,升本 英利,金光 ひでお,植山 浩二,池田 義,湊谷 謙司.
    • Organizer
      第70回日本胸部外科学会定期学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] 胸腹部大動脈瘤人工血管置換術におけるCritical segmental arteryの確実な術中同定法2017

    • Author(s)
      山下 剛生,湊谷 謙司,山﨑 和裕,金光 ひでお,中津 太郎,坂本 和久,井出 雄二郎,植山 浩二,池田 義
    • Organizer
      第70回日本胸部外科学会定期学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] Recombinant human soluble thrombomodulin prevents acute lung injury in a rat cardiopulmonary bypass model2016

    • Author(s)
      Hirao S, Minakata K, Masumoto H, Setozaki S, Yamazaki K, Ikeda T, Sakata R
    • Organizer
      AHA Scientific session 2016
    • Place of Presentation
      New Orleans, USA
    • Year and Date
      2016-11-12
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] ラット人工心肺モデルにおける遺伝子組換えトロンボモデュリン投与による急性肺障害抑制効果の検討2016

    • Author(s)
      平尾 慎吾,南方 謙二,升本 英利,船本 成輝,瀬戸﨑 修司,坂本 和久,中津 太郎,上原 京勲,山﨑 和裕,池田 義,坂田 隆造
    • Organizer
      第69回日本胸部外科学会定期学術集会
    • Place of Presentation
      岡山市
    • Year and Date
      2016-09-28
    • Related Report
      2016 Research-status Report
  • [Presentation] Recombinant human soluble thrombomodulin prevents acute lung injury induced by cardiopulmonary bypass in rats2016

    • Author(s)
      Hirao S, Minakata K, Masumoto H, Setozaki S, Yamazaki K, Ikeda T, Sakata R.
    • Organizer
      European Society of Cardiology Congress
    • Place of Presentation
      Rome, Italy
    • Year and Date
      2016-08-26
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Recombinant human soluble thrombomodulin prevents acute lung injury induced by cardiopulmonary bypass in a rat model2016

    • Author(s)
      Hirao S, Minakta K, Funamoto M, Setozaki S, Yamazaki K, Masumoto H, Ikeda T, Sakata R.
    • Organizer
      24th Anual meeting of Asian Society for Cardiovascular and Thoracic Surgery
    • Place of Presentation
      Taipei, Taiwan
    • Year and Date
      2016-04-06
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Use of extracorporeal membrane oxygeneration in complicated transcatheter aortic valve replacement2016

    • Author(s)
      Uehara K, Minakata K, Saito N, Imai M, Daijo H, Nakatsu T, Sakamoto K, Nakata T, Yamazaki K, Ikeda T, Kimura T
    • Organizer
      24th Anual meeting of Asian Society for Cardiovascular and Thoracic Surgery
    • Place of Presentation
      Taipei, Taiwan
    • Year and Date
      2016-04-06
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Remarks] http://kyoto-cvs.jp/

    • Related Report
      2018 Annual Research Report

URL: 

Published: 2016-04-21   Modified: 2020-03-30  

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