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Regulation of cardiac remodeling by inhibiting the PGD2-mediated inflammatory response.

Research Project

Project/Area Number 16K15199
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field General pharmacology
Research InstitutionThe University of Tokyo

Principal Investigator

Ikeda Yuichi  東京大学, 医学部附属病院, 特任准教授 (10744419)

Co-Investigator(Kenkyū-buntansha) 熊谷 英敏  東京大学, 医学部附属病院, 特任助教 (20281008)
森田 啓行  東京大学, 医学部附属病院, 講師 (60323573)
篠原 正和  神戸大学, 医学(系)研究科(研究院), 研究員 (80437483)
Co-Investigator(Renkei-kenkyūsha) URADE Yoshihiro  筑波大学, 国際統合睡眠医科学研究機構, 教授 (10201360)
Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords自己免疫性心筋炎 / 心筋線維化 / プロスタグランディンD2 / H-PGDS阻害薬 / 炎症・免疫 / プロスタグランディン
Outline of Final Research Achievements

Inflammatory response to the cardiomyocyte injury accelerates cardiac remodeling, the pathological process which often determines the clinical course of heart failure. Utilizing the experimental autoimmune myocarditis in mice as a model system, we found that PGD2 produced by H-PGDS contributed to the pathogenesis of cardiac remodeling initiated by local inflammation. In this model, cardiac PGD2 levels were elevated, and the systemic administration of H-PGDS inhibitor decreased the levels of PGD2, resulting in less fibrotic changes in the heart. These findings suggest that inhibition of the local production of PGD2 in the heart is beneficial for suppressing cardiac remodeling. To test if we could generalize our present findings, we established another mouse model based on the mdx mice. Using our second model, we are currently planning to determine if other bioactive lipid mediators produced in the heart are also involved in the pathogenesis of cardiac remodeling.

Report

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

    (24 results)

All 2017 2016

All Journal Article (24 results) (of which Peer Reviewed: 24 results,  Acknowledgement Compliant: 7 results,  Open Access: 11 results)

  • [Journal Article] A Periodontal pathogen Porphyromonas gingivalis deteriorates Isoproterenol-Induced myocardial remodeling in mice2017

    • Author(s)
      Sato H, Suzuki JI, Aoyama N, Watanabe R, Kaneko M, Shiheido Y, Yoshida A, Wakayama K, Kumagai H, Ikeda Y, Akazawa H, Komuro I, Isobe M, Izumi Y
    • Journal Title

      Hypertens Res.

      Volume: 40 Issue: 1 Pages: 35-40

    • DOI

      10.1038/hr.2016.114

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] A peptide vaccine targeting angiotensin II attenuates the cardiac dysfunction induced by myocardial infarction.2017

    • Author(s)
      Watanabe R, Suzuki JI, Wakayama K, Maejima Y, Shimamura M, Koriyama H, Nakagami H, Kumagai H, Ikeda Y, Akazawa H, Morishita R, Komuro I, Isobe M.
    • Journal Title

      Sci Rep.

      Volume: 7 Issue: 1 Pages: 43920-43920

    • DOI

      10.1038/srep43920

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Role of Hormone-sensitive Lipase in Leptin-Promoted Fat Loss and Glucose Lowering2017

    • Author(s)
      Takanashi M, Taira Y, Okazaki S, Takase S, Kimura T, Li CC, Xu PF, Noda A, Sakata I, Kumagai H, Ikeda Y, Iizuka Y, Yahagi N, Shimano H, Osuga JI, Ishibashi S, Kadowaki T, Okazaki H
    • Journal Title

      Journal of Atherosclerosis and Thrombosis

      Volume: 24 Issue: 11 Pages: 1105-1116

    • DOI

      10.5551/jat.39552

    • NAID

      130006191603

    • ISSN
      1340-3478, 1880-3873
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dysbiosis and compositional alterations with aging in the gut microbiota of patients with heart failure.2017

    • Author(s)
      Kamo T, Akazawa H, Suda W, Saga-Kamo A, Shimizu Y, Yagi H, Liu Q, Nomura S, Naito AT, Takeda N, Harada M, Toko H, Kumagai H, Ikeda Y, Takimoto E, Suzuki JI, Honda K, Morita H, Hattori M, Komuro I.
    • Journal Title

      PLoS One.

      Volume: 12 Issue: 3 Pages: 0174099-0174099

    • DOI

      10.1371/journal.pone.0174099

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Generation and characterization of an antagonistic monoclonal antibody against an extracellular domain of mouse DP2 (CRTH2/GPR44) receptors for prostaglandin D22017

    • Author(s)
      Nagata N, Iwanari H, Kumagai H, Kusano-Arai O, Ikeda Y, Aritake K, Hamakubo T, Urade Y
    • Journal Title

      PLoS One

      Volume: 12 Issue: 4 Pages: 0175452-0175452

    • DOI

      10.1371/journal.pone.0175452

    • NAID

      120007129138

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Periodontitis deteriorates peripheral arterial disease in Japanese population via enhanced systemic inflammation2017

    • Author(s)
      Aoyama N, Suzuki JI, Kobayashi N, Hanatani T, Ashigaki N, Yoshida A, Shiheido Y, Sato H, Kumagai H, Ikeda Y, Akazawa H, Komuro I, Izumi Y, Isobe M
    • Journal Title

      Heart Vessels

      Volume: 32 Issue: 11 Pages: 1314-1319

    • DOI

      10.1007/s00380-017-1003-6

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Specific periodontopathic bacterial infection affects hypertension in male cardiovascular disease patients2017

    • Author(s)
      Aoyama Norio、Suzuki Jun-ichi、Kumagai Hidetoshi、Ikeda Yuichi、Akazawa Hiroshi、Komuro Issei、Minabe Masato、Izumi Yuichi、Isobe Mitsuaki
    • Journal Title

      Heart Vessels.

      Volume: 33 Issue: 2 Pages: 198-204

    • DOI

      10.1007/s00380-017-1042-z

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Detrimental effects of specific Periodontopathic bacterial infection on tachyarrhythmia compared to Bradyarrhythmia2017

    • Author(s)
      Aoyama Norio、Suzuki Jun-ichi、Kobayashi Naho、Hanatani Tomoya、Ashigaki Norihiko、Yoshida Asuka、Shiheido Yuka、Sato Hiroki、Kumagai Hidetoshi、Ikeda Yuichi、Akazawa Hiroshi、Komuro Issei、Minabe Masato、Izumi Yuichi、Isobe Mitsuaki
    • Journal Title

      BMC Cardiovascular Disorders

      Volume: 17 Issue: 1 Pages: 267-267

    • DOI

      10.1186/s12872-017-0703-2

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Three novel BMPR2 mutations associated with advanced pulmonary arterial hypertension2017

    • Author(s)
      Hara Hironori、Takeda Norifumi、Morita Hiroyuki、Hatano Masaru、Amiya Eisuke、Maki Hisataka、Minatsuki Shun、Taki Mizuri、Shiraishi Yasuyuki、Fujiwara Takayuki、Maemura Sonoko、Komuro Issei
    • Journal Title

      Human Genome Variation

      Volume: 4 Issue: 1 Pages: 17010-17010

    • DOI

      10.1038/hgv.2017.10

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A novel mutation of NFIX causes Sotos-like syndrome (Malan syndrome) complicated with thoracic aortic aneurysm and dissection2017

    • Author(s)
      Oshima Tsukasa、Hara Hironori、Takeda Norifumi、Hasumi Eriko、Kuroda Yukiko、Taniguchi Go、Inuzuka Ryo、Nawata Kan、Morita Hiroyuki、Komuro Issei
    • Journal Title

      Human Genome Variation

      Volume: 4 Issue: 1 Pages: 17022-17022

    • DOI

      10.1038/hgv.2017.22

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Omega-3 Polyunsaturated Fatty Acid and Coronary Atherosclerotic Plaques2017

    • Author(s)
      Nakao Tomoko、Morita Hiroyuki
    • Journal Title

      International Heart Journal

      Volume: 58 Issue: 6 Pages: 837-839

    • DOI

      10.1536/ihj.17-552

    • NAID

      130006251669

    • ISSN
      1349-2365, 1349-3299
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cost-Effectiveness Analysis of Cardiovascular Disease Treatment in Japan2017

    • Author(s)
      Kodera Satoshi、Kiyosue Arihiro、Ando Jiro、Akazawa Hiroshi、Morita Hiroyuki、Watanabe Masafumi、Komuro Issei
    • Journal Title

      International Heart Journal

      Volume: 58 Issue: 6 Pages: 847-852

    • DOI

      10.1536/ihj.17-365

    • NAID

      130006251670

    • ISSN
      1349-2365, 1349-3299
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of MYLK3 mutations in familial dilated cardiomyopathy2017

    • Author(s)
      Tobita Takashige、Nomura Seitaro、Morita Hiroyuki、Ko Toshiyuki、Fujita Takanori、Toko Haruhiro、Uto Kenta、Hagiwara Nobuhisa、Aburatani Hiroyuki、Komuro Issei
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 17495-17495

    • DOI

      10.1038/s41598-017-17769-1

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Safety and Effectiveness of Endovenous Laser Ablation Combined With Ligation for Severe Saphenous Varicose Veins in Japanese Patients2016

    • Author(s)
      Izumi M, Ikeda Y, Yamashita H, Asaoka Y, Fujishiro M, Shin M, Abo Y.
    • Journal Title

      International Heart Journal

      Volume: 57 Issue: 1 Pages: 87-90

    • DOI

      10.1536/ihj.15-282

    • NAID

      130005120984

    • ISSN
      1349-2365, 1349-3299
    • URL

      https://pure.teikyo.jp/en/publications/d84b0eb4-7d54-4d1f-991f-0186b7909879

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cacao polyphenols ameliorate autoimmune myocarditis in mice2016

    • Author(s)
      Zempo H, Suzuki J, Watanabe R, Wakayama K, Kumagai H, Ikeda Y, Akazawa H, Komuro I, Isobe M
    • Journal Title

      Hypertens Res

      Volume: 39 Issue: 4 Pages: 203-209

    • DOI

      10.1038/hr.2015.136

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Angiotensin II receptor blocker irbesartan attenuates cardiac dysfunction induced by myocardial infarction in the presence of renal failure2016

    • Author(s)
      Watanabe R, Suzuki J, Wakayama K, Kumagai H, Ikeda Y, Akazawa H, Komuro I, Isobe M
    • Journal Title

      Hypertens Res

      Volume: 39 Issue: 4 Pages: 237-244

    • DOI

      10.1038/hr.2015.141

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Toll-like receptor 4 signaling has a critical role in Porphyromonas gingivalis-accelerated neointimal formation after arterial injury in mice.2016

    • Author(s)
      Kobayashi N, Suzuki JI, Aoyama N, Sato H, Akimoto S, Wakayama K, Kumagai H, Ikeda Y, Akazawa H, Komuro I, Izumi Y, Isobe M.
    • Journal Title

      Hypertens Res

      Volume: 39 Issue: 10 Pages: 717-722

    • DOI

      10.1038/hr.2016.58

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Projections from single NUCB2/nesfatin-1 neuron in paraventricular nucleus to different brain regions involved in feeding2016

    • Author(s)
      Maejima Y, Kumamoto K, Takenoshita S, Shimomura K
    • Journal Title

      Brain Structure and Function

      Volume: in press Pages: 123-137

    • DOI

      10.1016/j.yjmcc.2016.03.017

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Periodontitis May Deteriorate Sinus of Valsalva Dilatation in Marfan Syndrome Patients2016

    • Author(s)
      Suzuki J, Imai Y, Aoki M, Fujita D, Takeda N, Aoyama N, Wakayama K, Ikeda Y, Kumagai H, Akazawa H, Izumi Y, Isobe M, Komuro I, Hirata Y
    • Journal Title

      International Heart Journal

      Volume: 57 Issue: 4 Pages: 456-460

    • DOI

      10.1536/ihj.15-395

    • NAID

      130006895913

    • ISSN
      1349-2365, 1349-3299
    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Current therapies and investigational drugs for peripheral arterial disease2016

    • Author(s)
      Suzuki J, Shimamura M, Suda H, Wakayama K, Kumagai H, Ikeda Y, Akazawa H, Isobe M, Komuro I, Morishita R
    • Journal Title

      Hypertens Res

      Volume: 39 Issue: 4 Pages: 183-191

    • DOI

      10.1038/hr.2015.134

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Understanding vascular diseases: Lessons from premature aging syndromes2016

    • Author(s)
      Ikeda Y, Kumagai H, Motozawa Y, Suzuki J, Akazawa H, Komuro I
    • Journal Title

      Can J Cardiol

      Volume: 32 Issue: 5 Pages: 1-9

    • DOI

      10.1016/j.cjca.2015.12.003

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Current Practices in the Management of Antithrombotic Therapy During the Periendoscopic Period for Patients With Cardiovascular Disease2016

    • Author(s)
      Ono S, Saito I, Ikeda Y, Fujishiro M, Komuro I, Koike K.
    • Journal Title

      International Heart Journal

      Volume: 57 Issue: 5 Pages: 530-534

    • DOI

      10.1536/ihj.16-057

    • NAID

      130005266608

    • ISSN
      1349-2365, 1349-3299
    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Growth Differentiation Factor 15 (GDF15) as a Reliable Biomarker for Cardiovascular Risk Assessment2016

    • Author(s)
      Ikeda Y1, Kumagai H, Motozawa Y, Suzuki J
    • Journal Title

      International Heart Journal

      Volume: 57 Issue: 1 Pages: 1-2

    • DOI

      10.1536/ihj.15-324

    • NAID

      130005120988

    • ISSN
      1349-2365, 1349-3299
    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Re-bleeding After Endoscopic Hemostasis for Peptic Ulcer Bleeding: Is eNough SAID or Are Other Factors Important?2016

    • Author(s)
      Fujishiro M, Ikeda Y.
    • Journal Title

      Dig Dis Sci.

      Volume: 61 Issue: 6 Pages: 1424-1425

    • DOI

      10.1007/s10620-016-4098-1

    • Related Report
      2016 Research-status Report
    • Peer Reviewed

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Published: 2016-04-21   Modified: 2019-03-29  

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