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Myocardial interstitial serotonin kinetics and cardiomyocyte injury during ischemia-reperfusion in rats

Research Project

Project/Area Number 17K11604
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Emergency medicine
Research InstitutionNational Cardiovascular Center Research Institute

Principal Investigator

Akiyama Tsuyoshi  国立研究開発法人国立循環器病研究センター, 研究所, 客員研究員 (70202554)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords心虚血・再灌流 / セロトニン / 血小板 / トランスポーター / 心筋細胞傷害 / マイクロダイアリシス法 / 心虚血▪再灌流 / セロトニン(5-HT)
Outline of Final Research Achievements

Serotonin (5-HT) accumulates in the heart during myocardial ischemia and induces deleterious effects on the cardiomyocytes through receptor-dependent and monoamine oxidase-dependent pathways. During myocardial ischemia, depletion of ATP inhibits both sodium-potassium ATPase of cell membrane and ATP dependent vesicle transport of vesicle membrane and causes carrier-mediated 5-HT efflux from platelet via reverse-mode of 5-HT reuptake transporter, which is sensitive to the selective 5-HT reuptake inhibitor. During myocardial reperfusion, accumulated interstitial 5-HT is taken up into cardiac cells via plasma membrane monoamine transporter, one of extra-neuronal monoamine transporters and then metabolized by monoamine oxidase to produce 5-hydroxyindole acetic acid and hydrogen peroxide, which causes myocardial cell injury.

Academic Significance and Societal Importance of the Research Achievements

急性心筋梗塞症の急性期治療において、心筋細胞傷害を減弱させることは、その後の心不全への移行を防ぎ、予後を改善させることが可能であるが、いまだにその有効な治療法は見つかっていない。我々の心虚血・再灌流時における虚血部セロトニン動態の研究成果から、虚血時のセロトニン放出、および再灌流時におけるセロトニン代謝を抑制して、心筋細胞傷害を減弱させることが可能であり、急性心筋梗塞症急性期の新たな治療法につながると考えられる。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (13 results)

All 2020 2019 2018 2017

All Journal Article (8 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 7 results,  Open Access: 1 results) Presentation (5 results)

  • [Journal Article] Serotonin uptake via plasma membrane monoamine transporter during myocardial ischemia-reperfusion in the rat heart in vivo.2019

    • Author(s)
      Sonobe T, Akiyama T, Du CK, Pearson JT.
    • Journal Title

      Physiological Reports

      Volume: 7 Issue: 22 Pages: 1057-1069

    • DOI

      10.14814/phy2.14297

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Accentuated antagonism of vagal heart rate control and less potent prejunctional inhibition of vagal acetylcholine release during sympathetic nerve stimulation in the rat.2019

    • Author(s)
      Kawada T, Sonobe T, Hayama Y, Nishikawa T, Miyamoto T, Akiyama T, Pearson JT, Sugimachi M
    • Journal Title

      Autonomic neuroscience : basic & clinical

      Volume: 218 Pages: 25-30

    • DOI

      10.1016/j.autneu.2019.02.005

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Modulation of Sympathetic Activity and Innervation With Chronic Ivabradine and β-Blocker Therapies: Analysis of Hypertensive Rats With Heart Failure2019

    • Author(s)
      Kakehi Kazuyoshi、Iwanaga Yoshitaka、Watanabe Heitaro、Sonobe Takashi、Akiyama Tsuyoshi、Shimizu Shuji、Yamamoto Hiromi、Miyazaki Shunichi
    • Journal Title

      Journal of Cardiovascular Pharmacology and Therapeutics

      Volume: in press Issue: 4 Pages: 387-396

    • DOI

      10.1177/1074248419829168

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Central activation of cardiac vagal nerve by α2-adrenergic stimulation is impaired in streptozotocin-induced type 1 diabetic rats.2019

    • Author(s)
      Kawada T, Akiyama T, Sonobe T, Shimizu S, Hayama Y, Pearson JT, Shishido T, Sugimachi M
    • Journal Title

      Autonomic Neuroscience

      Volume: 219 Pages: 39-45

    • DOI

      10.1016/j.autneu.2018.09.001

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Mild hypothermia is ineffective to protect against myocardial injury induced by chemical anoxia or forced calcium overload.2019

    • Author(s)
      Kawada T, Yamazaki T, Akiyama T, Hayama Y, Sugimachi M
    • Journal Title

      Journal of Cardiovascular Pharmacology

      Volume: 73 Issue: 2 Pages: 100-104

    • DOI

      10.1097/fjc.0000000000000639

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Cardiac vagal control in a knock-in mouse model of dilated cardiomyopathy with a troponin mutation.2017

    • Author(s)
      Zhan DY, Du CK, Akiyama T, Morimoto S, Shimizu S, Kawada T, Shirai M, Pearson JT.
    • Journal Title

      Auton Neurosci.

      Volume: 205 Pages: 33-40

    • DOI

      10.1016/j.autneu.2017.03.002

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Desipramine increases cardiac parasympathetic activity via alpha2-adrenergic mechanism in rats.2017

    • Author(s)
      Kawada T, Akiyama T, Shimizu S,Fukumitsu M, Kamiya A, Sugimachi M.
    • Journal Title

      Auton Neurosci

      Volume: 99 Pages: 999-999

    • DOI

      10.1016/j.autneu.2017.02.005

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] 綜説「心臓マイクロダイアリシス法の利点」2017

    • Author(s)
      秋山 剛、清水 秀二、杜 成坤、戦 冬雲、稲垣 董克、吉本 光佐、曽野部 崇、川田 徹、ピアソン ジェームズ
    • Journal Title

      循環制御

      Volume: 38 Pages: 208-217

    • Related Report
      2017 Research-status Report
  • [Presentation] 虚血再灌流時の心筋間質における細胞膜モノアミン輸送体を介したセロトニン取り込み.2020

    • Author(s)
      曽野部 崇, 秋山 剛, Pearson James.
    • Organizer
      第97回 日本生理学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Evaluation of cardiac function in a knock-in mouse model for human DCM at early postnatal stages2019

    • Author(s)
      Cheng-Kun Du
    • Organizer
      第92回日本薬理学会年会
    • Related Report
      2018 Research-status Report
  • [Presentation] Carrier-mediated serotonin efflux from platelets in the heart.2018

    • Author(s)
      Sonobe T
    • Organizer
      第95回日本生理学会大会
    • Related Report
      2017 Research-status Report
  • [Presentation] alpha2C-Adrenoceptors play a key role in alpha2-adrenergic agonist-induced cardiac autonomic nervous responses.2018

    • Author(s)
      Shimizu S
    • Organizer
      第82回日本循環器学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] Cardiac-specific micrRNAs significantly increase after myocardial reperfusion in the ischemic region.2018

    • Author(s)
      Shimizu S
    • Organizer
      第82回日本循環器学会学術集会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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