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2015 Fiscal Year Annual Research Report

心不全における腸内細菌叢の機能的役割の解明

Research Project

Project/Area Number 26670395
Research InstitutionThe University of Tokyo

Principal Investigator

赤澤 宏  東京大学, 医学部附属病院, 講師 (20396683)

Project Period (FY) 2014-04-01 – 2016-03-31
Keywords循環器・高血圧
Outline of Annual Research Achievements

心不全患者22人(男性18人、女性4人)から便検体の提供を受けた。まずは健常者12名(41.6 + 2.0歳)と年齢をマッチさせた心不全患者12名(47.4 + 2.8歳)との間でマイクロバイオーム解析を行った。心不全患者の重症度はNew York Heart Association分類でII~IV度(平均2.9 + 0.2度)、心エコーでの左室収縮率は20 + 2 %、BNP値は1061 + 239 pg/mLであった。便検体から細菌叢ゲノムDNAを抽出して、16S rRNA領域を増幅したPCR産物(16Sアンプリコン)を対象として配列解析を行い、菌種(OTU)数から菌種数の推定、系統樹組成から細菌叢全体構造の比較(UniFrac-朱座標、距離解析)を行った。その結果、心不全患者と健常者との間でOTUの数に有意差は無かったが、心不全患者と健常者のUniFrac距離は健常者どうしのUniFrac距離よりも大きく、心不全患者の腸内細菌叢に構成異常が生じていることが明らかとなった。とくに心不全患者ではFirmicutes門Clostridia網に属する細菌の割合が減少していた。さらに60歳未満の若齢心不全患者12名(47.4 + 2.8歳)と60歳以上の高齢心不全患者10名(73.8 + 2.8歳)とで比較すると、両群間でも省内細菌叢が異なっており、とくに高齢患者ではBacteroidetes門Faecalibacterium属の割合が少なく、Proteobacteria門Lactobacillus属の割合が多いことが明らかとなった。心不全における血行動態の異常が腸内細菌叢の構成異常を引き起こし、そのことが心不全をさらに進展させるという「心腸連関」という新しい概念の妥当性を指示する実験結果であり、さらに心不全においては加齢によっても腸内細菌叢が変容することが示唆された。

  • Research Products

    (34 results)

All 2016 2015

All Journal Article (21 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 21 results,  Acknowledgement Compliant: 5 results,  Open Access: 5 results) Presentation (12 results) (of which Int'l Joint Research: 1 results,  Invited: 6 results) Book (1 results)

  • [Journal Article] Direct left atrial ICE imaging guided ablation for atrial fibrillation without employing contrast medium.2016

    • Author(s)
      Matsubara TJ, Fujiu K, Asada K, et al.
    • Journal Title

      Int J Cardiol

      Volume: 203 Pages: 733-739

    • DOI

      10.1016/j.ijcard.2015.11.038

    • Peer Reviewed
  • [Journal Article] Cacao polyphenols ameliorate autoimmune myocarditis in mice.2016

    • Author(s)
      Zempo H, Suzuki J, Watanabe R, et al.
    • Journal Title

      Hypertens Res

      Volume: 印刷中 Pages: 印刷中

    • Peer Reviewed
  • [Journal Article] Suppression of murine autoimmune myocarditis achieved with direct renin inhibition.2016

    • Author(s)
      Takamura C, Suzuki J, Ogawa M, et al.
    • Journal Title

      J Cardiol

      Volume: 印刷中 Pages: 印刷中

    • Peer Reviewed
  • [Journal Article] Cardiac arrest triggered by subepicardial aneurysm without cardiac rupture.2016

    • Author(s)
      Hasumi E, Fujiu K, Imamura T, et al.
    • Journal Title

      Circ J

      Volume: 印刷中 Pages: 印刷中

    • Peer Reviewed
  • [Journal Article] Angiotensin II receptor blocker irbesartan attenuates cardiac dysfunction induced by myocardial infarction in the presence of renal failure.2016

    • Author(s)
      Watanabe R, Suzuki J, Wakayama K, et al.
    • Journal Title

      Hypertens Res

      Volume: 印刷中 Pages: 印刷中

    • Peer Reviewed
  • [Journal Article] Toll-like receptor 4 signaling plays a critical role in Porphyromonas gingivalis accelerated neointimal formation after arterial injury in mice.2016

    • Author(s)
      Kobayashi N, Suzuki J, Aoyama N, et al.
    • Journal Title

      Hypertens Res

      Volume: 印刷中 Pages: 印刷中

    • Peer Reviewed
  • [Journal Article] Activation of endothelial β-catenin signaling induces heart failure.2016

    • Author(s)
      Nakagawa A, Naito AT, Sumida T, et al.
    • Journal Title

      Sci Rep

      Volume: 印刷中 Pages: 印刷中

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Pleiotropic effects of angiotensin II receptor signaling in cardiovascular homeostasis and aging.2015

    • Author(s)
      Kano T, Akazawa H, Komuro I
    • Journal Title

      Int Heart J

      Volume: 56 Pages: 249-254

    • DOI

      10.1536/ihj.14-429

    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Congenital contractural arachnodactyly without FBN1 or FBN2 Gene mutations complicated by dilated cardiomyopathy.2015

    • Author(s)
      Yagi H, Hatano M, Takeda N, et al.
    • Journal Title

      Intern Med

      Volume: 54 Pages: 1237-1241

    • DOI

      10.2169/internalmedicine.54.4280

    • Peer Reviewed
  • [Journal Article] Monitoring beta-arrestin recruitment via beta-lactamase enzyme fragment complementation: purification of peptide E as a low-affinity ligand for mammalian bombesin receptors.2015

    • Author(s)
      Ikeda Y, Kumagai H, Okazaki H, et al.
    • Journal Title

      PLoS One

      Volume: 10 Pages: e0127445

    • DOI

      10.1371/journal.pone.0127445

    • Peer Reviewed / Open Access
  • [Journal Article] Quantitative Measurement of GPCR Endocytosis via Pulse-Chase Covalent Labeling.2015

    • Author(s)
      Kumagai H, Ikeda Y, Motozawa Y, et al.
    • Journal Title

      PLoS One

      Volume: 10 Pages: e0129394

    • DOI

      10.1371/journal.pone.0129394

    • Peer Reviewed / Open Access
  • [Journal Article] Cardiac Non-myocytes in the Hub of Cardiac Hypertrophy.2015

    • Author(s)
      Kamo T, Akazawa H, Komuro I
    • Journal Title

      Circ Res

      Volume: 117 Pages: 89-98

    • DOI

      10.1161/CIRCRESAHA.117.305349

    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Wnt/β-catenin signaling contributes to skeletal myopathy in heart failure via direct interaction with FoxO.2015

    • Author(s)
      Okada K, Naito AT, Higo T, et al.
    • Journal Title

      Circ Heart Fail

      Volume: 8 Pages: 799-808

    • DOI

      10.1161/CIRCHEARTFAILURE.114.001958

    • Peer Reviewed
  • [Journal Article] Pirfenidone exhibits cardioprotective effects by regulating myocardial fibrosis and vascular permeability in pressure overloaded hearts.2015

    • Author(s)
      Yamagami K, Oka T, Wang Q, et al.
    • Journal Title

      Am J Physiol Heart Circ Physiol

      Volume: 309 Pages: H512-H522

    • DOI

      10.1152/ajpheart.00137.2015

    • Peer Reviewed
  • [Journal Article] Myocardial energy provision is preserved by increased utilization of glucose and ketone bodies in CD36 knockout mice.2015

    • Author(s)
      Nakatani K, Watabe T, Masuda D, et al.
    • Journal Title

      Metabolism

      Volume: 64 Pages: 1165-1174

    • DOI

      10.1016/j.metabol.2015.05.017

    • Peer Reviewed
  • [Journal Article] Angiotensin II receptor blockade promotes repair of skeletal muscle through down-regulation of aging-promoting C1q expression.2015

    • Author(s)
      Yabumoto C, Akazawa H, Yamamoto R, et al.
    • Journal Title

      Sci Rep

      Volume: 5 Pages: 14453

    • DOI

      10.1038/srep14453

    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Monocyte-derived extracellular Nampt-dependent biosynthesis of NAD+ protects the heart against pressure overload.2015

    • Author(s)
      Yano M, Akazawa H, Oka T, et al.
    • Journal Title

      Sci Rep

      Volume: 5 Pages: 15857

    • DOI

      10.1038/srep15857

    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Incidence of periodontitis in Japanese patients with cardiovascular diseases: a comparison between abdominal aortic aneurysm and arrhythmia.2015

    • Author(s)
      Suzuki J, Aoyama N, Aoki M, et al.
    • Journal Title

      Heart Vessels

      Volume: 30 Pages: 498-502

    • DOI

      10.1007/s00380-014-0507-6

    • Peer Reviewed
  • [Journal Article] High incidence and severity of periodontitis in Marfan syndrome patients in Japan.2015

    • Author(s)
      Suzuki J, Imai Y, Aoki M, et al.
    • Journal Title

      Heart Vessels

      Volume: 30 Pages: 692-695

    • DOI

      10.1007/s00380-013-0434-y

    • Peer Reviewed
  • [Journal Article] Identification of a novel compound that inhibits both mitochondria-mediated necrosis and apoptosis.2015

    • Author(s)
      Arakawa S, Nakanomyo I, Kudo-SakamotoY, et al.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 467 Pages: 1006-1011

    • DOI

      10.1016/j.bbrc.2015.10.022

    • Peer Reviewed
  • [Journal Article] Mechanisms of cardiovascular homeostasis and pathophysiology: from gene expression, signal transduction to cellular communication.2015

    • Author(s)
      Akazawa H
    • Journal Title

      Circ J

      Volume: 79 Pages: 2529-2536

    • DOI

      10.1253/circj.CJ-15-0818

    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] Cardiomyocyte Angiotensin II Type 1 Receptor Plays an Integrative Role in Post-myocardial Infarction Remodeling2016

    • Author(s)
      Hiroshi Akazawa, Masamichi Yano, Seitaro Nomura, Issei Komuro
    • Organizer
      Gordon Research Conference on Angiotensin
    • Place of Presentation
      Renaissance Tuscany (Il Ciocco, Italy)
    • Year and Date
      2016-02-21 – 2016-02-26
    • Int'l Joint Research
  • [Presentation] 心筋リモデリングにおけるカルパイン・カルパスタチンシステムの機能と役割2015

    • Author(s)
      赤澤 宏
    • Organizer
      Cardiovascular and Metabolic Week 2015 心血管代謝週間
    • Place of Presentation
      神戸国際会議場(兵庫県神戸市)
    • Year and Date
      2015-12-10 – 2015-12-12
    • Invited
  • [Presentation] 老化から疾患を考える~老化促進分子とRASの関係2015

    • Author(s)
      赤澤 宏
    • Organizer
      Cardiovascular and Metabolic Week 2015 心血管代謝週間
    • Place of Presentation
      神戸国際会議場(兵庫県神戸市)
    • Year and Date
      2015-12-10 – 2015-12-12
    • Invited
  • [Presentation] Monocyte-derived Extracellular Nampt-dependent Biosynthesis of Myocardial NAD+ Protects the Heart against Pressure Overload2015

    • Author(s)
      藪本千鶴、赤澤 宏、矢野正道、小室一成
    • Organizer
      Cardiovascular and Metabolic Week 2015 心血管代謝週間
    • Place of Presentation
      神戸国際会議場(兵庫県神戸市)
    • Year and Date
      2015-12-10 – 2015-12-12
  • [Presentation] Monocyte-derived extracellular Nampt-dependent biosynthesis of myocardial NAD+ protects the heart against pressure overload2015

    • Author(s)
      矢野正道、赤澤 宏、藪本千鶴、坂田泰史、小室一成
    • Organizer
      第19回日本心不全学会学術集会
    • Place of Presentation
      グランフロント大阪(大阪府大阪市)
    • Year and Date
      2015-10-22 – 2015-10-24
  • [Presentation] Inflammatory network underlying the pathogenesis of atrial fibrillation in stressed hearts2015

    • Author(s)
      赤澤 宏
    • Organizer
      第38回日本高血圧学会総会
    • Place of Presentation
      ひめぎんホール(愛媛県松山市)
    • Year and Date
      2015-10-09 – 2015-10-11
    • Invited
  • [Presentation] 単球由来eNamptによる圧負荷心の恒常性維持機構2015

    • Author(s)
      赤澤 宏
    • Organizer
      第38回日本高血圧学会総会
    • Place of Presentation
      ひめぎんホール(愛媛県松山市)
    • Year and Date
      2015-10-09 – 2015-10-11
  • [Presentation] Monocyte-derived Extracellular Nampt-dependent Biosynthesis of Myocardial NAD+ is Essential for Hemodynamic Compensation to Pressure Overload2015

    • Author(s)
      藪本千鶴、赤澤 宏、矢野正道、小室一成
    • Organizer
      第5回Molecular Cardiovascular Conference II
    • Place of Presentation
      ヒルトン福岡シーホーク(福岡県福岡市)
    • Year and Date
      2015-09-04 – 2015-09-05
  • [Presentation] Inflammatory network underlying the pathogenesis of atrial fibrillation2015

    • Author(s)
      赤澤 宏
    • Organizer
      第30回日本不整脈学会学術大会・第32回日本心電学会学術集会
    • Place of Presentation
      国立京都国際会館(京都府京都市)
    • Year and Date
      2015-07-28 – 2015-07-31
    • Invited
  • [Presentation] 老化形質発現におけるRASとWntの役割2015

    • Author(s)
      赤澤 宏
    • Organizer
      第36回日本炎症・再生医学会
    • Place of Presentation
      虎ノ門ヒルズフォーラム(東京都港区)
    • Year and Date
      2015-07-21 – 2015-07-22
    • Invited
  • [Presentation] 心臓のストレス応答から探る創薬ターゲット2015

    • Author(s)
      赤澤 宏
    • Organizer
      第1回国際心血管薬物療法学会日本部会学術集会
    • Place of Presentation
      ハイアットリージェンシー京都(京都府京都市)
    • Year and Date
      2015-06-20 – 2015-06-21
    • Invited
  • [Presentation] Molecular Mechanisms of Cardiovascular Stress Responses and Pathophysiology2015

    • Author(s)
      赤澤 宏
    • Organizer
      第79回日本循環器学会学術集
    • Place of Presentation
      大阪国際会議場(大阪府大阪市)
    • Year and Date
      2015-04-24 – 2015-04-26
  • [Book] Annual Review 循環器 20162015

    • Author(s)
      高橋政夫、赤澤 宏、小室一成
    • Total Pages
      280 (55-61)
    • Publisher
      中外医学社

URL: 

Published: 2017-01-06  

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