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Development of novel therapy for prevention of atherosclerosis via modulating gut bacterial flora and intestinal immunity

Research Project

Project/Area Number 24591114
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionKobe University

Principal Investigator

YAMASHITA Tomoya  神戸大学, 医学部附属病院, 准教授 (90437468)

Co-Investigator(Kenkyū-buntansha) SASAKI Naoto  神戸大学, 大学院医学研究科, 助教 (00514746)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords動脈硬化 / 腸内細菌 / 腸管免疫 / 制御性T細胞 / 免疫寛容性樹状細胞 / 腸内細菌叢 / 冠動脈疾患 / プロバイオティクス / 腸内細菌細菌叢 / プロバイオティックス
Outline of Final Research Achievements

We investigated the effects of oral treatment of materials that affect the intestinal immunity or change the gut bacterial flora using the atherosclerosis animal models. Antibiotics against gram-negative bacteria (Neomycin) treatment reduced the atherosclerotic lesion formation in mice, whereas antibiotics against gram-positive bacteria (Vancomycin) treatment had no effect. Now the mechanisms of the experimental results are under investigation. Based on the animal experiments, we examined the association between the incidence of coronary artery diseases (CAD) and the gut bacterial flora types. Compared with normal healthy control person, the content of order Lactobacillales was significantly increased and that of phylum Bacteroidetes was decreased in CAD patients. Further analyses should be needed to attain the therapeutic intervention to gut bacterial flora for prevention of atherosclerotic CAD.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (36 results)

All 2015 2014 2013 2012

All Journal Article (17 results) (of which Peer Reviewed: 7 results,  Open Access: 3 results,  Acknowledgement Compliant: 2 results) Presentation (18 results) (of which Invited: 6 results) Book (1 results)

  • [Journal Article] Foxp3+ regulatory T cells play a protective role in angiotensin II-induced aortic aneurysm formation in mice.2015

    • Author(s)
      Yodoi K, Yamashita T, Sasaki N, Kasahara K, Emoto T, Matsumoto T, Kita T, Sasaki Y, Mizoguchi T, Sparwasser T, Hirata K.
    • Journal Title

      Hypertension

      Volume: 65 Issue: 4 Pages: 889-895

    • DOI

      10.1161/hypertensionaha.114.04934

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Regulatory T cells and tolerogenic dendritic cells as critical immune modulators in atherogenesis.2015

    • Author(s)
      Sasaki N, Yamashita T, Kasahara K, Takeda M, Hirata K.
    • Journal Title

      Curr Pharm Des.

      Volume: 21 Pages: 1107-1117

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Regulatory/effector T-cell ratio is reduced in coronary artery disease.2014

    • Author(s)
      Emoto T, Sasaki N, Yamashita T, Kasahara K, Yodoi K, Sasaki Y, Matsumoto T, Mizoguchi T, Hirata K.
    • Journal Title

      Circulation Journal

      Volume: 78 Pages: 2935-2941

    • NAID

      130004699205

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] 短鎖脂肪酸と生活習慣病2014

    • Author(s)
      江本 拓央, 山下 智也, 平田 健一
    • Journal Title

      内分泌・糖尿病・代謝内科

      Volume: 39 Pages: 415-421

    • Related Report
      2014 Annual Research Report
  • [Journal Article] 腸内細菌と動脈硬化2014

    • Author(s)
      山下 智也
    • Journal Title

      Therapeutic Research

      Volume: 35 Pages: 789-791

    • Related Report
      2014 Annual Research Report
  • [Journal Article] 腸から動脈硬化は予防できるのか2014

    • Author(s)
      山下 智也, 笠原 和之, 佐々木 直人, 平田 健一
    • Journal Title

      医学のあゆみ

      Volume: 251 Pages: 100-106

    • Related Report
      2014 Annual Research Report
  • [Journal Article] 腸内細菌と動脈硬化 腸内細菌は新たな心血管病の治療標的となり得るか2014

    • Author(s)
      笠原 和之, 山下 智也, 佐々木 直人, 平田 健一
    • Journal Title

      生物の科学

      Volume: 68 Pages: 358-362

    • Related Report
      2014 Annual Research Report
  • [Journal Article] 腸内細菌と動脈硬化 腸から動脈硬化は予防できるのか?2014

    • Author(s)
      山下 智也, 平田 健一
    • Journal Title

      肥満研究

      Volume: 20 Pages: 7-12

    • Related Report
      2014 Annual Research Report
  • [Journal Article] 腸血管連関とその臨床的意義2014

    • Author(s)
      山下 智也, 平田 健一
    • Journal Title

      細胞工学

      Volume: 33 Pages: 529-534

    • Related Report
      2014 Annual Research Report
  • [Journal Article] 笠原 和之, 山下 智也, 佐々木 直人, 平田 健一2014

    • Author(s)
      プラーク形成・破裂と制御性T細胞
    • Journal Title

      The Lipid

      Volume: 25 Pages: 122-128

    • Related Report
      2014 Annual Research Report
  • [Journal Article] 腸内フローラへの介入と腸管免疫修飾による動脈硬化予防2014

    • Author(s)
      山下 智也, 笠原 和之, 佐々木 直人, 平田 健一
    • Journal Title

      腸内細菌学雑誌

      Volume: 28 Pages: 1-5

    • NAID

      130003392110

    • Related Report
      2014 Annual Research Report
  • [Journal Article] Regression of atherosclerosis with anti-CD3 antibody via augmenting a regulatory T-cell response in mice.2013

    • Author(s)
      Kita T, Yamashita T, Sasaki N, Kasahara K, Sasaki Y, Yodoi K, Takeda M, Nakajima K, Hirata K.
    • Journal Title

      Cardiovasc Res.

      Volume: 102 Issue: 1 Pages: 107-117

    • DOI

      10.1093/cvr/cvu002

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] CD3 antibody and IL-2 complex combination therapy inhibits atherosclerosis by augmenting a regulatory immune response.2013

    • Author(s)
      Kasahara K, Sasaki N, Yamashita T, Kita T, Yodoi K, Sasaki Y, Takeda M, Hirata K.
    • Journal Title

      J Am Heart Assoc.

      Volume: 3 Issue: 2

    • DOI

      10.1161/jaha.113.000719

    • Related Report
      2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 腸管免疫修飾による動脈硬化予防2013

    • Author(s)
      山下智也、平田健一
    • Journal Title

      医学のあゆみ

      Volume: 245 Pages: 189-190

    • Related Report
      2013 Research-status Report
  • [Journal Article] 腸管は心血管病予防の新たな治療ターゲットになる2013

    • Author(s)
      山下智也、佐々木直人、平田健一
    • Journal Title

      循環器専門医

      Volume: 21 Pages: 291-296

    • Related Report
      2013 Research-status Report
  • [Journal Article] Regulatory T cells in atherogenesis.2012

    • Author(s)
      Sasaki N, Yamashita T, Takeda M, Hirata K.
    • Journal Title

      J Atheroscler Thromb.

      Volume: 19 Pages: 503-15

    • NAID

      130004444608

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Dendritic cells in atherogenesis: possible novel targets for prevention of atherosclerosis.2012

    • Author(s)
      Takeda M, Yamashita T, Sasaki N, Hirata K.
    • Journal Title

      J Atheroscler Thromb.

      Volume: 19 Pages: 953-61

    • NAID

      130004444560

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] 腸内細菌叢への介入と腸管免疫修飾による動脈硬化予防2014

    • Author(s)
      山下智也、平田健一
    • Organizer
      第35回日本肥満学会
    • Place of Presentation
      宮崎シーガイヤ(宮崎)
    • Year and Date
      2014-10-24 – 2014-10-25
    • Related Report
      2014 Annual Research Report
  • [Presentation] 腸内細菌と動脈硬化2014

    • Author(s)
      山下智也、佐々木直人、平田健一
    • Organizer
      第46回日本動脈硬化学会総会
    • Place of Presentation
      京王プラザホテル(東京)
    • Year and Date
      2014-07-10 – 2014-07-11
    • Related Report
      2014 Annual Research Report
  • [Presentation] Regulatory T cells and CD4+CD28null T cells in coronary artery disease2014

    • Author(s)
      Takuo Emoto, Naoto Sasaki, Tomoya Yamashita, Kazuyuki Kasahara, Keiko Yodoi, Yoshihiro Sasaki, Takuya Matsumoto, Taiji Mizoguchi, Ken-ichi Hirata
    • Organizer
      第46回日本動脈硬化学会総会
    • Place of Presentation
      京王プラザホテル(東京)
    • Year and Date
      2014-07-10 – 2014-07-11
    • Related Report
      2014 Annual Research Report
  • [Presentation] 腸内フローラへの介入と腸管免疫修飾による動脈硬化予防2014

    • Author(s)
      山下智也、平田健一
    • Organizer
      第35回日本循環制御医学会総会
    • Place of Presentation
      九州大学医学部(福岡)
    • Year and Date
      2014-07-04 – 2014-07-05
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 腸から動脈硬化を予防する2014

    • Author(s)
      山下智也、平田健一
    • Organizer
      第56回日本老年医学会学術集会
    • Place of Presentation
      福岡国際会議場(福岡)
    • Year and Date
      2014-06-12 – 2014-06-14
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Novel therapeutic strategies for preventing atherosclerosis via modulating intestinal immunity and intervention to gut microflora.2013

    • Author(s)
      Tomoya Yamashita, Naoto Sasaki, Ken-ichi Hirata
    • Organizer
      第17回腸内細菌学会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] 腸管免疫修飾による動脈硬化予防法の開発研究2013

    • Author(s)
      山下智也
    • Organizer
      第13回日本抗加齢医学会総会
    • Place of Presentation
      横浜
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] Gut bacteria and their flora type as newly proposed risk factors in cardiovascular and metabolic diseases.2013

    • Author(s)
      Tomoya Yamashita, Ken-ichi Hirata
    • Organizer
      Annual Meeting of Korean Society of Obesity
    • Place of Presentation
      Seoul, Korea
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] Activation of skin dendritic cells controls atherogensis in mice.2013

    • Author(s)
      Naoto Sasaki, Tomoya Yamashita, Kazuyuki Kasahara, Tomoyuki Kita, Yoshihiro Sasaki, Keiko Yodoi, Ken-ichi Hirata.
    • Organizer
      Scientific Session of American Heart Association
    • Place of Presentation
      Dallas, Texas, USA
    • Related Report
      2013 Research-status Report
  • [Presentation] In vivo Expansion of Regulatory T Cells Attenuates Aortic Aneurysm Formation in Angiotensin II- Infused Apolipoprotein E-deficient Mice.2013

    • Author(s)
      Keiko Yodoi, Naoto Sasaki, Taiji Mizoguchi, Takuya Matsumoto, Takuo Emoto, Yoshihiro Sasaki, Kazuyuki Kasahara, Tomoyuki Kita, Tomoya Yamashita, Ken-ichi
    • Organizer
      Scientific Session of American Heart Association
    • Place of Presentation
      Dallas, Texas, USA
    • Related Report
      2013 Research-status Report
  • [Presentation] A novel combination therapy with anti-CD3 antibody and IL-2 complexes against atherosclerosis targeting effector T cells and regulatory T cells2013

    • Author(s)
      Kazuyuki Kasahara, Naoto Sasaki, Tomoya Yamashita, Yoshihiro Sasaki, Keiko Yodoi, Takuya Matsumoto, Takuo Emoto, Ken-ichi Hirata
    • Organizer
      Scientific Session of American Heart Association
    • Place of Presentation
      Dallas, Texas, USA
    • Related Report
      2013 Research-status Report
  • [Presentation] Intestine and skin could be novel therapeutic targets for preventing cardiovascular diseases.2013

    • Author(s)
      山下智也、佐々木直人、平田健一
    • Organizer
      第77回日本循環器学会学術集会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Related Report
      2012 Research-status Report
  • [Presentation] A novel combination therapy with anti-CD3 antibody and IL-2 complexes against atherosclerosis targeting effector T cells and regulatory T cells2013

    • Author(s)
      Kazuyuki Kasahara, Tomoya Yamashita, Naoto Sasaki, Tomoyuki Kita, Yoshihiro Sasaki, Keiko Yodoi, Takuo Emoto, Takuya Matsumoto, Ken-ichi Hirata
    • Organizer
      第77回日本循環器学会学術集会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Related Report
      2012 Research-status Report
  • [Presentation] A novel mouse model to deplete regulatory T cells uncovers their role in atherogenesis under hypercholesterolemia2013

    • Author(s)
      Kazuyuki Kasahara, Tomoya Yamashita, Naoto Sasaki, Tomoyuki Kita, Yoshihiro Sasaki, Keiko Yodoi, Takuo Emoto, Takuya Matsumoto, Ken-ichi Hirata
    • Organizer
      第77回日本循環器学会学術集会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Related Report
      2012 Research-status Report
  • [Presentation] In vivo expansion of regulatory T cells attenuates aortic aneurysm formation in angiotensin II- infused apolipoprotein E-deficient mice2013

    • Author(s)
      Keiko Yodoi, Tomoya Yamashita, Naoto Sasaki, Tomoyuki Kita, Kazuyuki Kasahara, Yoshihiro Sasaki, Takuo Emoto, Takuya Matsumoto, Ken-ichi Hirata
    • Organizer
      第77回日本循環器学会学術集会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Related Report
      2012 Research-status Report
  • [Presentation] 腸と皮膚からの免疫調節による新規動脈硬化予防法の開発研究2012

    • Author(s)
      山下智也
    • Organizer
      日本食品免疫学会第5回シンポジウム
    • Place of Presentation
      東京
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] 腸管免疫修飾による新規動脈硬化予防法の開発2012

    • Author(s)
      山下智也、佐々木直人、平田健一
    • Organizer
      第44回日本動脈硬化学会総会
    • Place of Presentation
      シーホークホテル(福岡)
    • Related Report
      2012 Research-status Report
  • [Presentation] Activation of regulatory T cells by ultraviolet irradiation controls atherogenesis in mice2012

    • Author(s)
      Naoto Sasaki, Tomoya Yamashita, Kazuyuki Kasahara, Kenji Nakajima, Tomoyuki Kita, Yoshihiro Sasaki, Keiko Yodoi, Masafumi Takeda, Ken-ichi Hirata
    • Organizer
      第85回米国心臓学会議
    • Place of Presentation
      ロスアンゼルスコンベンションセンター(ロスアンゼルス、米国)
    • Related Report
      2012 Research-status Report
  • [Book] Annual Review 糖尿病・代謝・内分泌2013

    • Author(s)
      山下智也、平田健一
    • Total Pages
      229
    • Publisher
      中外医学社
    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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