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Development of a novel cardiovascular regenerative therapy by vagal nerve stimulation

Research Project

Project/Area Number 26461099
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

LI MEIHUA  国立研究開発法人国立循環器病研究センター, 研究所, 特任研究員 (60443496)

Co-Investigator(Kenkyū-buntansha) 稲垣 正司  国立研究開発法人国立循環器病研究センター, 研究所, 室長 (80359273)
鄭 燦  国立研究開発法人国立循環器病研究センター, 研究所, 特任研究員 (50443495)
Co-Investigator(Renkei-kenkyūsha) KAWADA TORU  国立研究開発法人国立循環器病研究センター, 循環動態制御部, 室長 (30243752)
UEMURA KAZUNORI  国立研究開発法人国立循環器病研究センター, 循環動態制御部, 室長 (10344350)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords迷走神経刺激 / 急性心筋梗塞 / 慢性心不全 / 心臓リモデリング / 心血管新生 / 心筋幹細胞 / 増殖・分化 / 炎症・アポトシス / アポトシス / 炎症
Outline of Final Research Achievements

We have demonstrated that vagal stimulation (VS) prevented the cardiac remodeling and death in post-myocardial infarction rats. However, the precise mechanisms of cardiac protection by VS have not been fully elucidated. To develop a novel cardiovascular regeneration therapy, this study examined that effects of VS on cardiovascular regeneration and cardiac remodeling in acute myocardial infarction (AMI)rats. We investigated that VS promotes cardiovascular regerertion through activation of endogenous cardiac stem cells (CSCs) and prevents cardiac remodeling and dysfunction in AMI rats. The preservation of cardiac function by VS in AMI rats may be mediated partly improve myocardial salvage and reduce myocardial infarct size by cardiovascular regeneration through activation of endogenous CSCs, suggesting that VS approach may be a novel cardiovascular regereration therapy for post AMI and chronic heart failure patients.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (25 results)

All 2017 2016 2015 2014

All Journal Article (7 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 7 results,  Open Access: 4 results,  Acknowledgement Compliant: 2 results) Presentation (18 results) (of which Int'l Joint Research: 9 results,  Invited: 1 results)

  • [Journal Article] Acute ivabradine treatment reduces heart rate without increasing atrial fibrillation inducibility irrespective of underlying vagal activity in dogs2017

    • Author(s)
      Uemura K, Inagaki M, Zheng C, Kawada T, Li M, Fukumitsu M, Sugimachi M
    • Journal Title

      Heart Vessels.

      Volume: 32 Issue: 4 Pages: 484-494

    • DOI

      10.1007/s00380-016-0922-y

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Acute arterial baroreflex-mediated changes in plasma catecholamine concentrations in a chronic rat model of myocardial infarction.2016

    • Author(s)
      Kawada T, Akiyama T, Li M, Zheng C, Turner MJ, Shirai M, Sugimachi M.
    • Journal Title

      Physiol Rep.

      Volume: 4(15) Issue: 15

    • DOI

      10.14814/phy2.12880

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Acute Effects of Vagotomy on Baroreflex Equilibrium Diagram in Rats with Chronic Heart Failure2016

    • Author(s)
      Kawada T, Li M, Zheng C, Sugimachi M
    • Journal Title

      Clin Med Insights Cardiol.

      Volume: 10 Pages: 139-47

    • DOI

      10.4137/cmc.s38443

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Calibration of baroreflex equilibrium diagram based on exogenous pressor agents in chronic heart failure rats2015

    • Author(s)
      Kawada T, Li M, Sata Y, Zheng C, Turner MJ, Shimizu S, Sugimachi M
    • Journal Title

      Clin Med Insights Cardiol

      Volume: 9(Suppl 1) Pages: 1-9

    • DOI

      10.4137/cmc.s18759

    • Related Report
      2015 Research-status Report 2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] A novel technique to predict pulmonary capillary wedge pressure utilizing central venous pressure and tissue Doppler tricuspid/mitral annular velocities.2015

    • Author(s)
      Uemura K, Inagaki M, Zheng C, Li M, Kawada T, Sugimachi M.
    • Journal Title

      Heart Vessels.

      Volume: 30 Issue: 4 Pages: 516-526

    • DOI

      10.1007/s00380-014-0525-4

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Adding the acetylcholinesterase inhibitor, donepezil, to losartan treatment markedly improves long-term survival in rats with chronic heart failure.2014

    • Author(s)
      Li M, Zheng C, Kawada T, Inagaki M, Uemura K, Sugimachi M.
    • Journal Title

      Eur J Heart Fail.

      Volume: 16

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Chronic vagal nerve stimulation improves baroreflex neural arc function in heart failure rats2014

    • Author(s)
      Kawada T, Li M, Zheng C, Shimizu S, Uemura K, Turner MJ, Yamamoto H, Sugimachi M
    • Journal Title

      J Appl Physiol (1985)

      Volume: 116(10) Issue: 10 Pages: 1308-1314

    • DOI

      10.1152/japplphysiol.00140.2014

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Presentation] Donepezil but not Metoprolol Improves Myocardial Salvage and Prevents Cardiac Remodeling after Reperfused Myocardial Infarction in Rats2017

    • Author(s)
      LI M, Zheng C, Kawada T, Inagaki M, Uemura K, Shishido T, Sugimachi
    • Organizer
      JCS 2017
    • Place of Presentation
      金沢
    • Year and Date
      2017-03-17
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Donepezil Markedly Prevents the Progression of Cardiac Remodeling and Improves Survival in Spontaneously Hypertensive Rats with Myocardial Infarction2017

    • Author(s)
      LI M, Zheng C, Kawada T, Inagaki M, Uemura K, Shishido T, Sugimachi
    • Organizer
      JCS 2017
    • Place of Presentation
      金沢
    • Year and Date
      2017-03-17
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Vagal Stimulation Promotes Cardiovascular Regeneration by Activation of Endogenous Cardiac Stem Cells in Acute Myocardial Infarction Rats2016

    • Author(s)
      Li M, Inagaki M, Zheng C, Kawada T, Uemura K, Shishido T, Sugimachi M
    • Organizer
      ESC 2016
    • Place of Presentation
      ローマ
    • Year and Date
      2016-08-27
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Donepezil Administration as a Novel Therapy for Improved Myocardial Salvage after Reperfused Myocardial Infarction2016

    • Author(s)
      Li M, Zheng C, Kawada T, Inagaki M, Uemura K, Shishido T, Sugimachi M
    • Organizer
      ESC 2016
    • Place of Presentation
      ローマ
    • Year and Date
      2016-08-27
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Contribution of Central Donepezil to Prevention of Cardiac Dysfunction and Improvement of Long-term Survival in Chronic Heart Failure Rats after Myocardial Infarction2016

    • Author(s)
      Li M, Inagaki M, Zheng C, Kawada T, Uemura K, Shishido T, Sugimachi M
    • Organizer
      ESC 2016
    • Place of Presentation
      ローマ
    • Year and Date
      2016-08-27
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Prognostic significance of thirst augmentation in chrnic heart failure rats2016

    • Author(s)
      Zheng C, Li M, Kawada T, Inagaki M, Uemura K, Sugimachi M
    • Organizer
      ESC 2016
    • Place of Presentation
      ローマ
    • Year and Date
      2016-08-27
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Drinking behavioral and hemodynamics responses to daily fluid restriction in chrnic heart failure rats2016

    • Author(s)
      Zheng C, Li M, Kawada T, Sugimachi M
    • Organizer
      ESC 2016
    • Place of Presentation
      ローマ
    • Year and Date
      2016-08-27
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Central Donepezil Infusion Prevents Progression of Cardiac Remodeling and Improves Long-term Survival in Chronic Heart Failure Rats with Myocardial Infarction2016

    • Author(s)
      Li M, Zheng C, Kawada T, Inagaki M, Uemura K, Shishido T, Sugimachi M.
    • Organizer
      The 80th Annual Scientific Meeting of the Japanise Circulation Society
    • Place of Presentation
      SENDAI, Japan
    • Year and Date
      2016-03-18
    • Related Report
      2015 Research-status Report
  • [Presentation] Novel Therapeutic Approach in Heart Failure: Pharmacological Parasympathetic Activation2015

    • Author(s)
      Li M, Zheng C, Sugimachi M.
    • Organizer
      BIT's 7th Annual International Congress of Cardiology-2015
    • Place of Presentation
      SHANGHAI, China
    • Year and Date
      2015-12-04
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Central donepezil infusion prevents progression of cardiac remodeling and dysfunction in chronic heart failure rats with extensive myocardial infarction2015

    • Author(s)
      Li M, Zheng C, Kawada T, Inagaki M, Uemura K, Shishido T, SUgimachi M.
    • Organizer
      ESC CONGRESS 2015
    • Place of Presentation
      LONDON
    • Year and Date
      2015-08-29
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] ドネペジルの早期投与による再灌流心筋梗塞ラットにおける心臓リモデリングの抑制作用2015

    • Author(s)
      李梅花、鄭燦、川田徹、稲垣正司、上村和紀、宍戸稔聡、杉町勝
    • Organizer
      第36回日本循環制御医学会総会
    • Place of Presentation
      NAGOYA, Japan
    • Year and Date
      2015-06-05
    • Related Report
      2015 Research-status Report
  • [Presentation] Beneficial effects of Central Donepezil Infusion on Cardiac Remodeling in Chronic Heart Failure Rats with Extensive Myocardial Infarction2015

    • Author(s)
      Li M, Zheng C, Kawada T, Inagaki M, Uemura K, Shishido T, Sugimachi M.
    • Organizer
      HAKADA conference
    • Place of Presentation
      HUKUOKA, Japan
    • Year and Date
      2015-05-29
    • Related Report
      2015 Research-status Report
  • [Presentation] Early Donepezil Treatment is Superior to Metoprolol for Preventing Cardiac Remodeling in Reperfused Myocardial Infarction Rats2015

    • Author(s)
      Li M, et al.
    • Organizer
      The 79th Ammual Scientific Meeting of the Japanise
    • Place of Presentation
      Osaka, Japan
    • Year and Date
      2015-04-24 – 2015-04-26
    • Related Report
      2014 Research-status Report
  • [Presentation] Early Donepezil Treatment is Superior to Metoprolol for Preventing Cardiac Remodeling in Reperfused Myocardial Infarction Rats2015

    • Author(s)
      Li M, Zheng C, Kawada T, Inagaki M, Uemura K, Sugimachi M.
    • Organizer
      The 79th Annual Scientific Meeting of the Japanise Circulation Society
    • Place of Presentation
      OSAKA, Japan
    • Year and Date
      2015-04-24
    • Related Report
      2015 Research-status Report
  • [Presentation] ドネペジル中枢投与の心保護作用における末梢性α7-ニコチン性アセチルコリン受容体の役割2015

    • Author(s)
      李梅花、その他5人
    • Organizer
      日本薬学会第135年会
    • Place of Presentation
      神戸、日本
    • Year and Date
      2015-03-25 – 2015-03-28
    • Related Report
      2014 Research-status Report
  • [Presentation] Peripheral α7-Nicotinic Acetylcholine Receptors Contribute to Cardio-Protective Effects of Central Donepezil Infusion in Chronic Heart Failure Rats2014

    • Author(s)
      Li M, Zheng C, Kawada T, Inagaki M, Uemura K, Sugimachi M.
    • Organizer
      AHA 2014
    • Place of Presentation
      Chicago, lllinois
    • Year and Date
      2014-11-15 – 2014-11-19
    • Related Report
      2014 Research-status Report
  • [Presentation] ドネペジル中枢投与の心保護における末梢性α7-ニコチン性アセチルコリン受容体の影響2014

    • Author(s)
      李梅花、その他5人
    • Organizer
      第35回日本循環制御医学会総会
    • Place of Presentation
      福岡、日本
    • Year and Date
      2014-07-04 – 2014-07-05
    • Related Report
      2014 Research-status Report
  • [Presentation] Early Chronic Vagal Stimulation Markedly Suppressed Arrhythmic Death and Prevented Cardiac Remodeling in Rats after Acute Myocardial Infarction2014

    • Author(s)
      Meihua Li, Masashi Inagaki, Can Zheng, Toru Kawada, Kazunori Uemura, Masaru Sugimachi.
    • Organizer
      第53回日本生体医工学会大会
    • Place of Presentation
      仙台、日本
    • Year and Date
      2014-06-24 – 2014-06-26
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2018-03-22  

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