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Impacts of Local Macrophage Proliferation on Atherosclerotic Plaque Progression and Obesity-associated Adipose Tissue Inflammation.

Research Project

Project/Area Number 25461361
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Metabolomics
Research InstitutionKumamoto University

Principal Investigator

Senokuchi Takafumi  熊本大学, その他の研究科, 助教 (00530320)

Co-Investigator(Kenkyū-buntansha) MATSUMURA Takeshi  熊本大学, 医学部付属病院, 講師 (20398192)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsマクロファージ増殖 / 動脈硬化 / インスリン抵抗性 / 脂肪浸潤マクロファージ / 動脈硬化症
Outline of Final Research Achievements

To verify the direct evidence of involvement of Mφ proliferation in atherosclerosis and adipose tissue inflammation, we have generated Tg mice whose Mφ proliferation is specifically suppressed by the macrophage-specific p27kip expression. The atherosclerotic plaque formation was significantly reduced by Mφ growth inhibition. Mφs were less accumulated and the necrotic core formation was significantly decreased in Tg mice. The HFD-fed Tg showed improved insulin sensitivity. The crown-like structure formations was significantly reduced in Tg along with decreased inflammatory cytokine expression in adipose tissue.
The excess inflammatory responses in the atherosclerotic lesion and the adipose tissue were ameliorated by Mφ growth inhibition. The local Mφ proliferation could be the common pathophysiological feature in the progression of atherosclerosis and dietary-induced insulin resistance.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (18 results)

All 2015 2014 2013

All Journal Article (3 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results,  Open Access: 3 results,  Acknowledgement Compliant: 2 results) Presentation (15 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Sirt7 Contributes to Myocardial Tissue Repair by Maintaining Transforming Growth Factor-β Signaling Pathway2015

    • Author(s)
      Araki S, Izumiya Y, Rokutanda T, Ianni A, Hanatani S, Kimura Y, Onoue Y, Senokuchi T, Yoshizawa T, Yasuda O, Koitabashi N, Kurabayashi M, Braun T, Bober E, Yamagata K, Ogawa H
    • Journal Title

      Circulation

      Volume: 132(12) Issue: 12 Pages: 1081-1093

    • DOI

      10.1161/circulationaha.114.014821

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Statins meditate anti-atherosclerotic action in smooth muscle cells by peroxisome proliferator-activated receptor-γ activation.2014

    • Author(s)
      Fukuda K, Matsumura T, Senokuchi T, Ishii N, Kinoshita H, Yamada S, Murakami S, Nakao S, Motoshima H, Kondo T, Kukidome D, Kawasaki S, Kawada T, Nishikawa T, Araki E
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 457 Issue: 1 Pages: 23-20

    • DOI

      10.1016/j.bbrc.2014.12.063

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] SIRT7 controls hepatic lipid metabolism by regulating the ubiquitin-proteasome pathway.2014

    • Author(s)
      Yoshizawa T, Karim Md. F, Sato Y, Senokuchi T, Miyata K, Fukuda T, Go C, Tasaki M, Uchimura K, Kadomatsu T, Tian Z, Smolka C, Sawa T, Kakeya M, Tomizawa K, Ando Y, Araki E, Akaike T, Braun T, Oike Y, Bober E, Yamagata K.
    • Journal Title

      Cell Metab.

      Volume: 9 Issue: 4 Pages: 712-721

    • DOI

      10.1016/j.cmet.2014.03.006

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] インスリン抵抗性および動脈硬化発症・進展におけるマクロファージ増殖の意義の検討2015

    • Author(s)
      瀬ノ口隆文、山田沙梨恵、松村 剛、本島寛之、石井規夫、 福田一起、村上彩子、守田雄一郎、西川武志、荒木栄一
    • Organizer
      第53回日本糖尿病学会 九州地方会
    • Place of Presentation
      福岡市
    • Year and Date
      2015-11-27
    • Related Report
      2015 Annual Research Report
  • [Presentation] Targeted Disruption of Macrophage Proliferation Ameliorates Atherosclerotic Plaque Progression and Obesity-associated Adipose Tissue Inflammation.2015

    • Author(s)
      Takafumi Senokuchi, Sarie Yamada, Takeshi Matsumura, Takeshi Nishikawa, Eiichi Araki
    • Organizer
      2016 Keystone Symposia Conference, T2 Diabetes: New Insights into Molecular Mechanisms and Therapeutic Strategies
    • Place of Presentation
      Kyoto, Japan
    • Year and Date
      2015-10-25
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Impacts of Local Macrophage Proliferation on Atherosclerotic Plaque Progression and Obesity-associated Adipose Tissue Inflammation.2015

    • Author(s)
      Sarie Yama, Takafumi Senokuchi, Takeshi Matsumura, Takeshi Nishikawa, Eiichi Araki
    • Organizer
      75th Scientific Sessions, American Diabetes Association
    • Place of Presentation
      Boston, U.S.A.
    • Year and Date
      2015-06-05 – 2015-06-09
    • Related Report
      2014 Research-status Report
  • [Presentation] Impacts of Local Macrophage Proliferation on Atherosclerotic Plaque Progression and Obesity-Associated Adipose Tissue Inflammation2015

    • Author(s)
      Sarie Yamada, Takafumi Senokuchi, Takeshi Matsumura, Takeshi Nishikawa, Eiichi Araki
    • Organizer
      American Diabetes Association 75th Scientific Sessions
    • Place of Presentation
      Boston, U.S.A.
    • Year and Date
      2015-06-05
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] インスリン抵抗性及び動脈硬化の発症・進展に対する組織浸潤マクロファージ増殖の生理学的意義の検討2015

    • Author(s)
      山田沙梨恵, 瀬ノ口隆文, 松村 剛, 本島寛之, 石井規夫, 木下博之, 福田一起, 西川武志, 荒木栄一
    • Organizer
      第58回日本糖尿病学会年次学術集会
    • Place of Presentation
      下関市
    • Year and Date
      2015-05-21 – 2015-05-24
    • Related Report
      2014 Research-status Report
  • [Presentation] インスリン抵抗性及び動脈硬化の発症・進展に対する組織浸潤マクロファージ増殖の 生理学的意義の検討2015

    • Author(s)
      山田 沙梨恵
    • Organizer
      第58回日本糖尿病学会年次学術集会
    • Place of Presentation
      下関市
    • Year and Date
      2015-05-21
    • Related Report
      2015 Annual Research Report
  • [Presentation] インスリン抵抗性、動脈硬化の発症・進展 における組織浸潤マクロファージ増殖の 生理学的意義の検討2014

    • Author(s)
      瀬ノ口 隆文、山田 沙梨恵、松村 剛、 本島 寛之、西川 武志、荒木 栄一
    • Organizer
      第26回分子糖尿病学シンポジウム
    • Place of Presentation
      高知市
    • Year and Date
      2014-12-06
    • Related Report
      2014 Research-status Report
  • [Presentation] Statin-mediated PPARγ activation in adipocytes may improve glucose tolerance in high fat-fed mice.2014

    • Author(s)
      Takafumi Senokuchi, Takeshi Matsumura, Kazuki Fukuda, Norio Ishii, Hiroyuki Kinoshita, Sarie Yamada, Saiko Murakami, Tatsuya Kondo, Hiroyuki Motoshima, Takeshi Nishikawa, Eiichi Araki
    • Organizer
      6th AASD Scientific Meeting
    • Place of Presentation
      Singapore
    • Year and Date
      2014-09-21 – 2014-09-24
    • Related Report
      2014 Research-status Report
  • [Presentation] Inhibition of Local Macrophage Growth Ameliorates Focal inflammation in the Plaque and Suppresses Atherosclerosis in ApoE-deficient Mice.2014

    • Author(s)
      Takafumi Senokuchi, Sarie Yamada, Emi Negita, Takeshi Matsumura, Takeshi Nishikawa, Eiichi Araki
    • Organizer
      9th Metabolic Syndrome, Type 2 Diabetes and Atherosclerosis Congress
    • Place of Presentation
      Kyoto, Japan
    • Year and Date
      2014-09-12 – 2014-09-13
    • Related Report
      2014 Research-status Report
  • [Presentation] 糖尿病における動脈硬化症進展の体質医学的研究 組織浸潤マクロファージ増殖の意義の検討2014

    • Author(s)
      瀬ノ口 隆文
    • Organizer
      第64回日本体質医学会総会
    • Place of Presentation
      大阪市
    • Year and Date
      2014-09-06 – 2014-09-07
    • Related Report
      2014 Research-status Report
  • [Presentation] 動脈硬化病変形成におけるマクロファージ増殖の病態生理学的意義の検討2014

    • Author(s)
      山田 沙梨恵、瀬ノ口 隆文、松村 剛、本島 寛之、石井 規夫、木下 博之、福田 一起、西川 武志、荒木 栄一
    • Organizer
      第46回日本動脈硬化学会総会・学術集会
    • Place of Presentation
      東京都
    • Year and Date
      2014-07-10 – 2014-07-11
    • Related Report
      2014 Research-status Report
  • [Presentation] 肥満•メタボリックシンドロームにおける 血清脂質値への コレステロール合成・吸収能の影響2013

    • Author(s)
      11. 瀬ノ口隆文, 松村剛, 本島寛之, 石井規夫, 木下博之, 福田一起, 金谷絢子, 佐藤恵子, 荒木栄一
    • Organizer
      第56回日本糖尿病学会年次学術集会
    • Place of Presentation
      熊本市
    • Related Report
      2013 Research-status Report
  • [Presentation] インスリン抵抗性マクロファージのFoxO活性化を介した アポトーシス誘導による動脈硬化進展機序の解明2013

    • Author(s)
      瀬ノ口隆文, 山田沙梨恵, 松村剛, 西川武志, 荒木栄一
    • Organizer
      第45回日本動脈硬化学会総会・学術集会
    • Place of Presentation
      東京都
    • Related Report
      2013 Research-status Report
  • [Presentation] マクロファージインスリン抵抗性による動脈硬化進展機序の検討2013

    • Author(s)
      瀬ノ口隆文, 山田沙梨恵, 松村剛, 西川武志, 荒木栄一
    • Organizer
      第28回日本糖尿病合併症学会
    • Place of Presentation
      旭川市
    • Related Report
      2013 Research-status Report
  • [Presentation] 肥満における血清脂質値へのコレステロール合成・吸収能の影響2013

    • Author(s)
      瀬ノ口隆文, 松村剛, 石井規夫, 本島寛之, 西川武志, 荒木栄一
    • Organizer
      第110回日本内科学会総会
    • Place of Presentation
      東京都
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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