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Developing successful immunomodulatory therapies against ventricular remodeling after myocardial infarction

Research Project

Project/Area Number 23390217
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionKeio University

Principal Investigator

SANO MOTOAKI  慶應義塾大学, 医学部, 准教授 (30265798)

Co-Investigator(Renkei-kenkyūsha) YAN Xiaoxiang  慶應義塾大学, 医学部, 大学院生 (90594979)
ANZAI Atsushi  慶應義塾大学, 医学部, 助教 (50528164)
Project Period (FY) 2011-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥19,240,000 (Direct Cost: ¥14,800,000、Indirect Cost: ¥4,440,000)
Fiscal Year 2013: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2012: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2011: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
Keywords心筋梗塞 / 心不全 / 免疫 / 肺水腫 / NK細胞 / 好中球 / IL-10 / 線維化 / 樹状細胞 / リンパ球 / マクロファージ
Research Abstract

Left ventricular (LV) remodeling leads to chronic heart failure and is a main determinant of morbidity and mortality after myocardial infarction (MI). Mice with DC ablation showed deteriorated LV function and remodeling concomitant with enhanced expression of IL-1beta, IL-18, and TNF-alpha, prolonged extracellular matrix degradation, marked infiltration of proinflammatory monocytes. A deficiency of gamma-delta T cells improved survival, limiting infarct expansion and fibrosis in noninfarcted myocardium and alleviating LV dilatation and systolic dysfunction after MI. IL-17A-producing gamma-delta T cells promotes sustained infiltration of neutrophils and macrophages, , aggravating cardiomyocyte death, and enhancing fibroblast proliferation. Depletion of NK cells from mice exhibited severe respiratory. Adoptive transfer of NK cells from wild-type mice, but not from IL-10 knockout mice, into the NK cell-depleted mice rescued the respiratory phenotype.

Report

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

    (23 results)

All 2014 2013 2012 2011 Other

All Journal Article (10 results) (of which Peer Reviewed: 10 results) Presentation (11 results) Book (1 results) Remarks (1 results)

  • [Journal Article] Lung natural killer cells play a major counter-regulatory role in pulmonary vascular hyperpermeability after myocardial infarction2014

    • Author(s)
      Yan X, Hegab AE, Endo J, Anzai A, Matsuhashi T, Katsumata Y, Ito K, Yamamoto T, Betsuyaku T, Shinmura K, Shen W, Vivier E, Fukuda K, Sano M
    • Journal Title

      Circ Res

      Volume: 114(4) Issue: 4 Pages: 637-49

    • DOI

      10.1161/circresaha.114.302625

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Temporal dynamics of cardiac immune cell accumulation following a cute myocardial infarction2013

    • Author(s)
      Yan X, Anzai A, Katsumata Y, Matsuhashi T, Ito K, Endo J, Yamamoto T, Takeshima A, Shinmura K, Shen W, Fukuda K, Sano M
    • Journal Title

      Journal of Molecular and Cellular Cardiology

      Volume: 62 Pages: 24-35

    • DOI

      10.1016/j.yjmcc.2013.04.023

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Diverse stage-dependent effects of glucocorticoids in a murine model of viral myocarditis.2013

    • Author(s)
      Hiroshi Nakamura
    • Journal Title

      Journal of Cardiology.

      Volume: -

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Deleterious Effect of the IL-23/IL-17A Axis and γδT Cells on Left Ventricular Remodeling After Myocardial Infarction2012

    • Author(s)
      Xiaoxiang Yan
    • Journal Title

      Journal of the American Heart Association

      Volume: 1(5) Issue: 5 Pages: 1-22

    • DOI

      10.1161/jaha.112.004408

    • Related Report
      2013 Final Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Regulatory Role of Dendritic Cells in Post-Infarction Healing and Left Ventricular Remodeling2012

    • Author(s)
      Anzai A, Fukuda K, et al
    • Journal Title

      Circulation

      Volume: 125(10) Issue: 10 Pages: 1234-1245

    • DOI

      10.1161/circulationaha.111.052126

    • Related Report
      2013 Final Research Report 2012 Annual Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Chronic salt loading in salt-sensitive rats paradoxically increases aldosterone production.2012

    • Author(s)
      Shintaro Morizane
    • Journal Title

      Arterioscler Thromb Vasc Biol

      Volume: 32(5) Issue: 5 Pages: 1194-203

    • DOI

      10.1161/atvbaha.111.242719

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Lipocalin-type prostaglandin D2 synthase promotes renal interstitial fibrosis via Th2 lymphocyte activation in unilateral ureteral obstruction.2012

    • Author(s)
      Hideyuki Ito
    • Journal Title

      J Am Soc Nephrol

      Volume: 23(11) Issue: 11 Pages: 1797-809

    • DOI

      10.1681/asn.2012020126

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Aldehyde-stress resulting from Aldh2 mutation promotes osteoporosis due to impaired osteoblastogenesis2012

    • Author(s)
      Hoshi H, Hao W, Fujita Y, Funayama A, Miyauchi Y, Hashimoto K, Miyamoto K, (他21名)
    • Journal Title

      J. Bone Miner Res

      Volume: 27(9) Issue: 9 Pages: 2015-2023

    • DOI

      10.1002/jbmr.1634

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Multifaceted approach to analyzing the pathogenesis of cardiovascular disease.2012

    • Author(s)
      Sano Motoaki
    • Journal Title

      Circ J.

      Volume: 76(11) Pages: 2521-9

    • NAID

      10031078380

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Distinct metabolic flow enables large scale purification of cardiomyocytes from pluripotent stem cell-derivatives.2012

    • Author(s)
      Shugo Tohyama
    • Journal Title

      Cell Stem Cell

      Volume: 12 Pages: 127-137

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Presentation] Lung natural killer cells play a major counter-regulatory role in pulmonary vascular hyperpermeability after myocardial infarction2014

    • Author(s)
      Motoaki Sano, Xiaoxiang Yan, Keiichi Fukuda
    • Organizer
      The 78Th Annual Scientific Meeting of the japanese Circulation Society
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report
  • [Presentation] Deleterious Effect of IL-23/IL-17 Axis and γ δ T Cells in Left Ventricular Remodeling after Myocardial Infarction2012

    • Author(s)
      Xiaoxiang Yan, Motoaki Sano, Takashi Shichita, Tomohiro Matsuhashi, Yoshinori Katsumata, Akihiko Yoshimura, Keiichi Fukuda
    • Organizer
      American Heart Association-Scientific Sessions
    • Place of Presentation
      Los angles, California, USA
    • Year and Date
      2012-11-06
    • Related Report
      2013 Final Research Report
  • [Presentation] IL-17 Produced from γ δ T cells Promote Left Ventricular Remodeling after Myocardial Infarction2012

    • Author(s)
      Xiaoxiang Yan, Motoaki Sano, Takashi Shichita, Tomohiro Matsuhashi, Yoshinori Katsumata, Akihiko Yoshimura, Keiichi Fukuda
    • Organizer
      The 76th Annual Scientific Meeting of the Japanese Circulation Society
    • Place of Presentation
      Fukuoka, Japan
    • Year and Date
      2012-03-16
    • Related Report
      2013 Final Research Report
  • [Presentation] IL-17 Produced from γδT Cells Promote Left Ventricular Remodeling after Myocardial Infarction2012

    • Author(s)
      〓小響
    • Organizer
      第76回日本循環器病学会
    • Place of Presentation
      福岡国際会議場
    • Year and Date
      2012-03-16
    • Related Report
      2011 Annual Research Report
  • [Presentation] Deleterious Effect of IL-23/IL-17 Axis and γ δ T Cells in Left Ventricular Remodeling after Myocardial Infarction2012

    • Author(s)
      Xiaoxiang Yan, Motoaki Sano, Takashi Shichita, Tomohiro Matsuhashi, Yoshinori Katsumata, Akihiko Yoshimura, Keiichi Fukuda
    • Organizer
      Ifrec-Sign Winter School on Advanced Immunology
    • Place of Presentation
      Awaji, Japan
    • Year and Date
      2012-01-18
    • Related Report
      2013 Final Research Report
  • [Presentation] Regulatory Role of Dendritic Cells in Post-Infarction Healing and Left Ventricular Remodeling2011

    • Author(s)
      Anzai A, Anzai T, Nagai S, Maekawa Y, Kaneko H, Sugano Y, Sano M, Yoshikawa T, Koyasu S, Fukuda K
    • Organizer
      第28回国際心臓研究学会日本部会YIAsession
    • Place of Presentation
      東京にて開催
    • Year and Date
      2011-12-03
    • Related Report
      2013 Final Research Report
  • [Presentation] Deleterious Effect of IL-23/IL-17 Axis and γ δ T Cells in Left Ventricular Remodeling after Myocardial Infarction2011

    • Author(s)
      Xiaoxiang Yan, Motoaki Sano, Takashi Shichita, Tomohiro Matsuhashi, Yoshinori Katsumata, Akihiko Yoshimura, Keiichi Fukuda
    • Organizer
      American Heart Association-Scientific Sessions
    • Place of Presentation
      Orlando, Florida, USA
    • Year and Date
      2011-11-15
    • Related Report
      2013 Final Research Report
  • [Presentation] Dendritic Cell is an Immunoprotective Regulator in Post-Infarction Healing and Left Ventricular Remodeling2011

    • Author(s)
      Anzai A, Anzai T, Nagai S, Maekawa Y, Sano M, Yoshikawa T, Koyasu S, Ogawa S, Fukuda K
    • Organizer
      American Heart Association-Scientific Sessions
    • Place of Presentation
      Orlando, Florida, USA
    • Year and Date
      2011-11-15
    • Related Report
      2013 Final Research Report
  • [Presentation] Selective Depletion of Dendritic Cells Resulted in Deteriorated Left Ventricular Remodeling after Myocardial Infarction2011

    • Author(s)
      Anzai A, Anzai T, Nagai S, Maekawa Y, Kaneko H, Sugano Y, Sano M, Yoshikawa T, Koyasu S, Fukuda K
    • Organizer
      第75回日本循環器学会総会
    • Place of Presentation
      横浜にて開催
    • Year and Date
      2011-08-03
    • Related Report
      2013 Final Research Report
  • [Presentation] Prostaglandin D2-F type prostanoid receptor signaling is a novel cardiomyocyte survival pathway.

    • Author(s)
      Yoshinori Katsumata
    • Organizer
      Basic cardiovascular sciences 2012 scientific sessions
    • Place of Presentation
      New Orleans, Louisiana.
    • Related Report
      2012 Annual Research Report
  • [Presentation] Cooperative Operation of PGD2/FP and 15d-PGJ2/nrf2 Pathway in the L-PGDS-Mediated Cardioprotection.

    • Author(s)
      Yoshinori Katsumata
    • Organizer
      American Heart Association scientific sessions
    • Place of Presentation
      Orlando, Florida
    • Related Report
      2012 Annual Research Report
  • [Book] 心筋梗塞後リモデリングにおける免疫細胞の役割心臓2012

    • Author(s)
      佐野元昭, 安西淳, Xiaoxiang Yan
    • Publisher
      日本心臓財団
    • Related Report
      2013 Final Research Report
  • [Remarks]

    • URL

      http://www.cpnet.med.keio.ac.jp/

    • Related Report
      2013 Final Research Report

URL: 

Published: 2011-04-06   Modified: 2019-07-29  

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