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Novel Strategy to prevent ischemia/reperfusion injury that overcomes disadvantages of antioxidant agents

Research Project

Project/Area Number 23592672
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Emergency medicine
Research InstitutionOita University

Principal Investigator

TAKAHASHI NAOHIKO  大分大学, 医学部, 教授 (30263239)

Co-Investigator(Kenkyū-buntansha) TESHIMA Yasushi  大分大学, 医学部, 助教 (10457608)
HAGIWARA Satoshi  大分大学, 医学部, 講師 (50527661)
SAIKAWA Tetsunori  大分大学, 医学部, 教授 (60145365)
NOGUCHI Takayuki  大分大学, 医学部, 教授 (90156183)
Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords心房細動 / メタボリック症候群 / 酸化ストレス / 虚血再灌流障害
Research Abstract

We examined the hypothesis that leptin signaling contributes to the atrial fibrosis and atrial fibrillation (AF) evoked by angiotensin II (AngII). Male CL57/B6 (CNT) and leptin-deficient ob/ob mice (Ob) were subcutaneously infused with AngII. In CNT-AngII mice, leptin expression in the left atrium was upregulated. Transesophageal burst pacing induced AF in 88% of CNT-AngII mice, but not in Ob-AngII mice (0%). In isolated perfused hearts, AF was induced only in CNT-AngII mice (67%). Inter-atrial conduction time was prolonged in CNT-AngII mice, but not in Ob-AngII mice. In cultured SD rat atrial fibroblasts, AngII treatment increased leptin expression. Addition of leptin increased TGF-beta1, alpha-SMA, MCP-1 and RANTES expressions in SD rat atrial fibroblasts but not in Zucker rat atrial fibroblasts. These observations demonstrate that leptin signaling is essential for the development of atrial fibrosis and AF evoked by AngII.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (22 results)

All 2014 2013 2012 2011

All Journal Article (8 results) (of which Peer Reviewed: 6 results) Presentation (14 results)

  • [Journal Article] Production of reactive oxygen species in the diabetic heart. Roles of mitochondria and NADPH oxidase2014

    • Author(s)
      Teshima Y, Takahashi N, Nishio S, Saito S, Kondo H, Fukui A, Aoki K, Yufu K, Nakagawa M, Saikawa T
    • Journal Title

      Circ J

      Volume: 78(2) Pages: 300-306

    • NAID

      130003382238

    • Related Report
      2013 Final Research Report
  • [Journal Article] Production of reactive oxygen species in the diabetic heart. Roles of mitochondria and NADPH oxidase.2014

    • Author(s)
      Teshima Y et al
    • Journal Title

      Circ J

      Volume: 78 Pages: 300-306

    • NAID

      130003382238

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Role of leptin signaling in the pathogenesis of angiotensin II-mediated atrial fibrosisand fibrillation2013

    • Author(s)
      Fukui A, Takahashi N, Nakada C, Masaki T, Kume O, Shinohara T, Teshima Y, Hara M, Saikawa T
    • Journal Title

      Circ Arrhythm Electrophysiol

      Volume: 6(2) Pages: 402-409

    • Related Report
      2013 Final Research Report
  • [Journal Article] Role of Leptin Signaling in the Pathogenesis of Angiotensin II-Mediated Atrial Fibrosis and Fibrillation.2013

    • Author(s)
      Fukui A, Takahashi N, Nakada C, Masaki T, Kume O, Shinohara T, Teshima Y, Hara M, Saikawa T.
    • Journal Title

      Circ Arrhythm Electrophysiol

      Volume: 2 Issue: 2 Pages: 402-9

    • DOI

      10.1161/circep.111.000104

    • Related Report
      2013 Annual Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Establishment of a model of atrial fibrillation associated with chronic kidney disease in rats and the role of oxidative stress.2012

    • Author(s)
      Fukunaga N, Takahashi N, Hagiwara S, Kume O, Fukui A, Teshima Y, Shinohara T, Nawata T, Hara M, Noguchi T, Saikawa T.
    • Journal Title

      Heart Rhythm

      Volume: 12 Issue: 12 Pages: 2023-31

    • DOI

      10.1016/j.hrthm.2012.08.019

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Inhibition of Na(+) -H(+) exchange as a mechanism of rapid cardioprotection by resveratrol.2012

    • Author(s)
      Thuc LC, Teshima Y, Takahashi N, Nishio S, Fukui A, Kume O, Saito S, Nakagawa M, Saikawa T
    • Journal Title

      Br J Pharmacol

      Volume: Epub ahead Issue: 6 Pages: 1745-1755

    • DOI

      10.1111/j.1476-5381.2012.01877.x

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Activation of CaMKII as a key regulator of reactive oxygen species production in diabetic rat heart.2012

    • Author(s)
      Nishio S, Teshima Y, Takahashi N, Thuc LC, Saito S, Fukui A, Kume O, Fukunaga N, Hara M, Nakagawa M, Saikawa T.
    • Journal Title

      J Mol Cell Cardiol

      Volume: 52 Pages: 1103-1111

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Candesartan restored cardiac Hsp72 expression and tolerance against reperfusion injury in hereditary insulin-resistant rats.2011

    • Author(s)
      Taniguchi Y, Takahashi N, Fukui A, Nagano-Torigoe Y, Thuc LC, Teshima Y, Shinohara T, Wakisaka O, Ooie T, Murozono Y, Yufu K, Nakagawa M, Hara M, Yoshimatsu H, Saikawa T.
    • Journal Title

      Cardiovasc Res

      Volume: 23 Pages: 433-435

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] Takahashi N. Hyperleptinemia exacerbates high fat diet-mediated atrial remodeling and fibrillation2014

    • Author(s)
      Fukui A, Kondo H, Saito S, Nishio S, Shinohara T, Teshima Y, Saikawa T
    • Organizer
      第78回日本循環器学会総会・学術集会
    • Place of Presentation
      東京
    • Related Report
      2013 Final Research Report
  • [Presentation] Role of spleen-derived Interleukin-10 in high-fat-diet-induced inflammatory atrial fibrosis and fibrillation2014

    • Author(s)
      Kondo H, Takahashi N, Saito S, Fukui A, Nishio S, Aoki K, Shinohara T, Teshima Y, Hara M, Saikawa T
    • Organizer
      第78回日本循環器学会総会・学術集会
    • Place of Presentation
      東京
    • Related Report
      2013 Final Research Report
  • [Presentation] Interleukin-10 treatment attenuates sinus node dysfunction and atrial fibrillation vulnerability caused by streptozotocin-induced hyperglycemia2014

    • Author(s)
      Kondo H, Saito S, Fukui A, Nishio S, Shinohara T, Teshima Y, Takahashi N
    • Organizer
      第78回日本循環器学会総会・学術集会
    • Place of Presentation
      東京
    • Related Report
      2013 Final Research Report
  • [Presentation] Glucose fluctuations aggravate atrial fibrillation in animal models of Type 1 and Type 2 diabetes mellitus2014

    • Author(s)
      Saito S, Teshima Y, Nishio S, Kondo H, Fukui A, Nakagawa M, Saikawa T, Takahashi N
    • Organizer
      第78回日本循環器学会総会・学術集会
    • Place of Presentation
      東京
    • Related Report
      2013 Final Research Report
  • [Presentation] Role of indoxyl sulfate, a major uremic toxin, in pathogenesis of atrial fibrillation associated with chronic kidney disease2014

    • Author(s)
      Aoki K, Takahashi N, Kondo H, Saito S, Nishio S, Fukui A, Shinohara T, Teshima Y, Shibata T
    • Organizer
      第78回日本循環器学会総会・学術集会
    • Place of Presentation
      東京
    • Related Report
      2013 Final Research Report
  • [Presentation] Hyperleptinemia Exacerbates high Fat Diet-mediated Atrial Remodeling and Fibrillation.2014

    • Author(s)
      Fukui A et al
    • Organizer
      日本循環器学会総会・学術集会
    • Place of Presentation
      東京国際フォーラム、東京
    • Related Report
      2013 Annual Research Report
  • [Presentation] Role of Spleen in Atrial Fibrosis and Fibrillation.2014

    • Author(s)
      Kondo H et al
    • Organizer
      日本循環器学会総会・学術集会
    • Place of Presentation
      東京国際フォーラム、東京
    • Related Report
      2013 Annual Research Report
  • [Presentation] Interleukin-10 Treatment Attenuates Sinus Node Dysfunction and Atrial Fibrillation Vulnerability Caused by Steptozotocin-Induced Hyperglycemia.2014

    • Author(s)
      Kondo H et al
    • Organizer
      日本循環器学会総会・学術集会
    • Place of Presentation
      東京国際フォーラム、東京
    • Related Report
      2013 Annual Research Report
  • [Presentation] Glucose Fluctuations Aggravate Atrial Fibrillation in Animal Models of Type 1 and Type 2 Diabetes Mellitus.2014

    • Author(s)
      Saito S et al
    • Organizer
      日本循環器学会総会・学術集会
    • Place of Presentation
      東京国際フォーラム、東京
    • Related Report
      2013 Annual Research Report
  • [Presentation] Role of Indoxyl Sulfate, a Major Uremic Toxin, in Pathogenesis2014

    • Author(s)
      Aoki K et al
    • Organizer
      日本循環器学会総会・学術集会
    • Place of Presentation
      東京国際フォーラム、東京
    • Related Report
      2013 Annual Research Report
  • [Presentation] Role of H1 and H2 Receptors in Pathogenesis of Pressure Overload-mediated Atrial Fibrosis and Fibrillation.2013

    • Author(s)
      Fukui A, Takahashi N, Masaki T, Konfo H, Saito S, Nishio S< Shinohara T, Teshima Y, Hara M, Saikawa T.
    • Organizer
      第77回日本循環器学会学術集会
    • Place of Presentation
      横浜
    • Related Report
      2012 Research-status Report
  • [Presentation] Glucose Fluctuations Aggravate Cardiac Fibrosis Resulting in Worse Outcomes Including Atrial Fibrillation in Diabetic Rats.2013

    • Author(s)
      Saito S, Teshima Y, Takahashi N, Nishio S, Kondo H, Fukui A, Hara M, Nakagawa M, Saikawa T.
    • Organizer
      第77回日本循環器学会学術集会
    • Place of Presentation
      横浜
    • Related Report
      2012 Research-status Report
  • [Presentation] Role of Leptin Signaling in Pathogenesis of Atrial Fibrosis and Fibrillation.2012

    • Author(s)
      Fukui A, Takahashi N, Fukunaga N, Thuc L, Kume O, Miyazaki H, Wzaki K, Shinohara T, Teshima Y, Yufu K, Hara M, Nakagawa M, Yoshimatsu H, Saikawa T.
    • Organizer
      第76回日本循環器学会学術集会
    • Place of Presentation
      福岡
    • Related Report
      2012 Research-status Report
  • [Presentation] Role of Leptin Signaling in Pathogenesis of Atrial Fibrosis and Fibrillation2011

    • Author(s)
      Fukui A, Takahashi N, Teshima Y, Yufu K, Nakagawa M, Saikawa T, Kume O, Wakisaka O, Shinohara T, Hara M, Yoshimatsu H.
    • Organizer
      Annual meeting of American Heart Associatoin
    • Place of Presentation
      orlando
    • Related Report
      2011 Research-status Report

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Published: 2011-08-05   Modified: 2019-07-29  

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