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Development of a novel therapeutics for vascular diseases by anti-inflammatory molecules and a new gene-delivery system

Research Project

Project/Area Number 19590867
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

ICHIKI Toshihiro  Kyushu University, 大学院・医学研究院, 客員准教授 (80311843)

Co-Investigator(Kenkyū-buntansha) 江頭 健輔  九州大学, 医学研究院, 准教授 (60260379)
Co-Investigator(Renkei-kenkyūsha) EGASHIRA Kensuke  九州大学, 医学研究院, 准教授 (60260379)
Project Period (FY) 2007 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2007: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywordsベラプロスト / inducible cAMP early repressor / レスベラトロール / SIRT1 / アンジオテンシンII 受容体 / アンジオテンシンII / アンジオテンシンII受容体 / Liver X receptor / p16 / SP-1 / Mst1 / アポトーシス / siRNA / 血管平滑筋細胞 / 血管内皮細胞
Research Abstract

(1) プロスタサイクリンの誘導体であるべラプロストはinducible cAMP early repressor(ICER)の発現を誘導し、ICER の過剰発現は血管平滑筋細胞の増殖とバルーン傷害後の新生内膜形成を抑制した。
(2) レスベラトロールおよびレスベラトロールが活性化する長寿遺伝子SIRT1 の過剰発現は血管平滑筋細胞におけるアンジオテンシンII 受容体の発現を抑制した。レスべラトロールはアンジオテンシンII による血圧上昇や冠動脈周囲の線維化を抑制した。
ICER やレスべラトロールが血管における炎症を抑制し、動脈硬化の治療に有用であることが示唆された。

Report

(3 results)
  • 2008 Annual Research Report   Final Research Report ( PDF )
  • 2007 Annual Research Report
  • Research Products

    (44 results)

All 2009 2008 2007 Other

All Journal Article (13 results) (of which Peer Reviewed: 12 results) Presentation (31 results)

  • [Journal Article] Improvement of Neovascularization Capacity of Bone Marrow Mononuclear Cells from Diabetic Mice by ex vivo Pretreatment with Resveratrol2009

    • Author(s)
      Gan L, Matsuura H, Ichiki T, Yin X, Miyazaki R, Hashimoto T, Juan C, Takeda K, Sunagawa K
    • Journal Title

      Hypertension Research (In Press)

    • NAID

      10025163921

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Resveratrol attenuates angiotensin II- induced interleukin- 6 expression and perivascular fibrosis2009

    • Author(s)
      Inanaga K, Ichiki T, Matsuura H, Miyazaki R, Hashimoto T, Takeda K Sunagawa K
    • Journal Title

      Hypertension Research (In press)

    • NAID

      10024831068

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] SIRT1, a Longevity Gene, Downregulates Angiotensin II Type 1 Receptor Expression in Vascular Smooth Muscle Cells2008

    • Author(s)
      Miyazaki R, Ichiki T, Hashimoto T, Inanaga K, Imayama I, Sadoshima J, Sunagawa K
    • Journal Title

      Arterioscler Thromb Vasc Biol 28

      Pages: 1263-1269

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Liver X Receptor Activator Downregulates Angiotensin II Type 1 Receptor Expression through Dephosphorylation of Sp12008

    • Author(s)
      Imayama I, Ichiki T, Patton D, Inanaga K, Miyazaki R, Ohtsubo H, Tian Q, Yano K, Sunagawa K
    • Journal Title

      Hypertension 51

      Pages: 1631-1636

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of Mst1 in tumor necrosis factor- alpha- induced apoptosis of endothelial cells2008

    • Author(s)
      Ohtsubo H, Ichiki T, Imayama I, Ono H, Fukuyama K, Hashiguchi Y, Sadoshima J, Sunagawa K
    • Journal Title

      Biochem Biophys Res Commun 367

      Pages: 474-80

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Liver X Receptor Activator Downregulates Angiotensin II Type 1 Receptor Expressionthrough Dephosphorylation of Spl2008

    • Author(s)
      Imayama I, Ichiki T. Patton D. Inanaga K, Miyazaki R, Ohtsubo H, Tian Q, Yano K, Sunagawa K.
    • Journal Title

      Hypertension 51

      Pages: 1631-1636

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] SIRT1, a Longevity Gene, Downregulates Angiotensin II Type 1 Receptor Expression inVascular Smooth Muscle Cells2008

    • Author(s)
      Miyazaki R, Ichiki T, Hashimoto T, Inanaga K, Imayama I, Sadoshima J, Sunagawa K
    • Journal Title

      Arteriosclerosis Thrombosis and Vascular Biology 28

      Pages: 1263-1269

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of Mstl in tumor necrosis factor-alpha-induced apoptosis of endothelialcells2008

    • Author(s)
      Ohtsubo H, Ichiki T. Imayama I, Ono H, Fukuyama K, Hashiguchi Y, Sadoshima J, Sunagawa K
    • Journal Title

      Biochemical and Biophysical Research Communication 367

      Pages: 474-480

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of Mst1 in tumor necrosis factor-alpha-induced apoptosis of endothelial cells2008

    • Author(s)
      Ohtsubo H, Ichiki T, Imayama I, Ono H, Fukuyama K, Hashiguchi Y, Sadoshima J, Sunagawa K
    • Journal Title

      Biochemical and Biophysical Research Communication 367

      Pages: 474-480

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Inhibition of Balloon Injury- Induced Neointimal Formation by Olmesartan and Pravastatin in Rats with Insulin Resistance2007

    • Author(s)
      Chen M, Ichiki T, Ohtsubo H, Imayama I, Inanaga K, Miyazaki M, Sunagawa K
    • Journal Title

      Hypertens Res 30

      Pages: 971-978

    • NAID

      10020168051

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Inducible cAMP Early Repressor Inhibits Growth of Vascular Smooth Muscle Cell2007

    • Author(s)
      Ohtsubo H, , Ichiki T, Miyazaki R, Inanaga K, Imayama I, Hashiguchi Y, Sadoshima J, Sunagawa K
    • Journal Title

      Arterioscler Thromb Vasc Biol 27

      Pages: 1549-1555

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Inducible cAMP Early Repressor Inhibits Growth of Vascular Smooth Muscle Cell2007

    • Author(s)
      Ohtsubo H, Ichiki T, Miyazaki R, Inanaga K, Imayama I, Hashiguchi Y, Sadoshima J, Sunagawa K.
    • Journal Title

      Arteriosclerosis Thrombosis and Vascular Biology 27

      Pages: 1549-1555

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Inhibition of TNF α- Induced Interleukin- 6 Expression by Telmisartan through Crosstalk of PPAR- γ with NF- κB and C/EBPβ

    • Author(s)
      Tian Q, Miyazaki R, Ichiki T , Imayama I, Inanaga K , Ohtsubo H, Yano K, Takeda K Sunagawa K
    • Journal Title

      Hypertension 53

      Pages: 798-804

    • Related Report
      2008 Final Research Report
  • [Presentation] Telmisartan Manifests Powerful Anti- inflammatory Effects Beyond Class Effects of Angiotensin II Type 1 Blocker by Inhibiting Tumor Necrosis Factor alpha- Induced Interleukin 6 Expressions through Peroxisome Proliferator Activated Receptory Activation. Circulation 20082009

    • Author(s)
      Ichiki T, Tian Q, Imayama I, Sunagawa K
    • Organizer
      AHA Scientific Sessions 2008(118;S513)
    • Place of Presentation
      ニューオーリンズ
    • Related Report
      2008 Final Research Report
  • [Presentation] Hashimoto T, Matsuura H, Sunagawa K. SIRT1, a Longevity Gene, Downregulates Angiotensin II Type 1 Receptor Expression. Circ J 20092009

    • Author(s)
      Myazaki R, Ichiki T, Takeda K, Inanaga K
    • Organizer
      第73回日本循環器学会(73:392)
    • Place of Presentation
      大阪
    • Related Report
      2008 Final Research Report
  • [Presentation] Telmisartan Inhibits Tumor necrosis factor alpha-induced intereleukin-6 expressinthrough PPARγ.2008

    • Author(s)
      Ichiki T, Tian Q, Imayama I, Sunagawa K
    • Organizer
      アメリカ心臓協会学術集会
    • Place of Presentation
      米国、ニューオーリンズ
    • Year and Date
      2008-11-11
    • Related Report
      2008 Annual Research Report
  • [Presentation] レスベラトロールはアンジオテンシンIIによるインターロイキン6の発現を抑制する2008

    • Author(s)
      稲永慶太, 市来俊弘, 砂川賢二
    • Organizer
      第31回日本高血圧学会総会
    • Place of Presentation
      札幌市
    • Year and Date
      2008-10-10
    • Related Report
      2008 Annual Research Report
  • [Presentation] テルミサルタンはperoxisome proliferators activated receptor gammaの活性化により腫瘍壊死因子によるインターロイキン6の発現を抑制する2008

    • Author(s)
      市来俊弘, 砂川賢二
    • Organizer
      第31回日本高血圧学会総会
    • Place of Presentation
      札幌市
    • Year and Date
      2008-10-09
    • Related Report
      2008 Annual Research Report
  • [Presentation] Role and regulation of cAMP response element binding protein in the formation ofvascular lesion2008

    • Author(s)
      市来俊弘
    • Organizer
      第40回日本動脈硬化学会
    • Place of Presentation
      筑波市
    • Year and Date
      2008-07-11
    • Related Report
      2008 Annual Research Report
  • [Presentation] Telmisartan Inhibits Tumor necrosis factor alpha-induced mtereleukm-6 expressionthrough PPARγ.2008

    • Author(s)
      Ichiki T, Tian Q, Imayama I, Sunagawa K
    • Organizer
      第22回国際高血圧学会
    • Place of Presentation
      ドイツ、ベルリン
    • Year and Date
      2008-06-17
    • Related Report
      2008 Annual Research Report
  • [Presentation] SIRT1, a longevity gene, downregulates angiotensin II type 1 receptorexpression2008

    • Author(s)
      Miyazaki R, Ichiki T, Sunagawa K
    • Organizer
      第22回国際高血圧学会
    • Place of Presentation
      ドイツ、ベルリン
    • Year and Date
      2008-06-17
    • Related Report
      2008 Annual Research Report
  • [Presentation] Telmisartan Inhibits Tumor necrosis factor alpha- induced intereleukin- 6 expressin through PPARg. J Hypertens 20082008

    • Author(s)
      Ichiki T, Tian Q, Imayama I, Sunagawa K
    • Organizer
      22^<nd> International Society of Hypertension Meeting(26:S314)
    • Place of Presentation
      ベルリン
    • Related Report
      2008 Final Research Report
  • [Presentation] SIRT1, a longevity gene, downregulates angiotensin II type 1 receptor expression . J Hypertens 20082008

    • Author(s)
      Miyazaki R, Ichiki T, Sunagawa K
    • Organizer
      22<nd>^ International Society of Hypertension Meeting(26:S521)
    • Place of Presentation
      ベルリン
    • Related Report
      2008 Final Research Report
  • [Presentation] Telmsiartan inhibits TNFalpha-induced interleukin-6 expression in vascular smooth muscle cells2008

    • Author(s)
      市来俊弘、今山郁代、砂川賢二
    • Organizer
      第72回日本循環器学会
    • Place of Presentation
      福岡
    • Related Report
      2008 Final Research Report
  • [Presentation] Role and regulation of cAMP response element binding protein in the formation of vascular lesion2008

    • Author(s)
      市来俊弘
    • Organizer
      第40回日本動脈硬化学会シンポジウム
    • Place of Presentation
      筑波
    • Related Report
      2008 Final Research Report
  • [Presentation] テルミサルタンはperoxisome proliferators activated receptor gamma の活性化により腫瘍壊 死因子によるインターロイキン6の発 現を抑制する。2008

    • Author(s)
      市来俊弘、砂川賢二
    • Organizer
      第31回日本高血圧学会総会
    • Place of Presentation
      札幌
    • Related Report
      2008 Final Research Report
  • [Presentation] レスベラトロールはアンジオテンシンII によるインターロイキン6の発現を抑制する。2008

    • Author(s)
      稲永慶太、市来俊弘、砂川賢二
    • Organizer
      第31回日本高血圧学会総会
    • Place of Presentation
      札幌
    • Related Report
      2008 Final Research Report
  • [Presentation] レスベラトロールはアンジオテンシンIIタイプ1受容体の発現を抑制する2007

    • Author(s)
      宮崎 良平、市来 俊弘、砂川 賢二
    • Organizer
      第15回日本血管生物医学会
    • Place of Presentation
      福岡
    • Year and Date
      2007-11-29
    • Related Report
      2007 Annual Research Report
  • [Presentation] レスベラトロールによるアンジオテンシンII タイプ1受容体の発現抑制に関する検討2007

    • Author(s)
      宮崎良平、市来俊弘、砂川賢二
    • Organizer
      第11回日本心血管内分泌代謝学会
    • Year and Date
      2007-11-16
    • Related Report
      2008 Final Research Report
  • [Presentation] レスベラトロールによるアンジオテンシンIIタイプ1受容体の発現抑制に関する検討2007

    • Author(s)
      宮崎 良平、市来 俊弘、砂川 賢二
    • Organizer
      第11回日本心血管内分泌代謝学会
    • Place of Presentation
      東京
    • Year and Date
      2007-11-16
    • Related Report
      2007 Annual Research Report
  • [Presentation] アンジオテンシンIIは血管における炎症反応を促進する。2007

    • Author(s)
      市來俊弘
    • Organizer
      第48回日本脈管学会
    • Year and Date
      2007-10-25
    • Related Report
      2008 Final Research Report
  • [Presentation] レスベラトロールによるアンジオテンシンII タイプ1受容体の発現抑制に関する検討2007

    • Author(s)
      宮崎良平、市来俊弘、砂川賢二
    • Organizer
      第30回日本高血圧学会
    • Year and Date
      2007-10-25
    • Related Report
      2008 Final Research Report
  • [Presentation] オルメサルタンは血管平滑筋細胞において高グルコース刺激によるMCP-1 の発現を抑制する2007

    • Author(s)
      市来俊弘、砂川賢二
    • Organizer
      第30回日本高血圧学会
    • Year and Date
      2007-10-25
    • Related Report
      2008 Final Research Report
  • [Presentation] アンジオテンシンIIは血管における炎症反応を促進する2007

    • Author(s)
      市来 俊弘
    • Organizer
      第48回日本脈管学会
    • Place of Presentation
      長野
    • Year and Date
      2007-10-25
    • Related Report
      2007 Annual Research Report
  • [Presentation] レスベラトロールによるアンジオテンシンIIタイプ1受容体の発現抑制に関する検討2007

    • Author(s)
      宮崎 良平、市来 俊弘、砂川 賢二
    • Organizer
      第30回日本高血圧学会
    • Place of Presentation
      沖縄
    • Year and Date
      2007-10-25
    • Related Report
      2007 Annual Research Report
  • [Presentation] オルメサルタンは血管平滑筋細胞において高グルコース刺激によるMCP-1の発現を抑制する2007

    • Author(s)
      市来 俊弘、砂川 賢二
    • Organizer
      第30回日本高血圧学会
    • Place of Presentation
      沖縄
    • Year and Date
      2007-10-25
    • Related Report
      2007 Annual Research Report
  • [Presentation] テルミサルタンはPPARγを介して血管平滑筋細胞のアンジオテンシンII タイプ1受容体の発現を抑制する2007

    • Author(s)
      市來俊弘、砂川賢二
    • Organizer
      第55回日本心臓病学会
    • Year and Date
      2007-09-10
    • Related Report
      2008 Final Research Report
  • [Presentation] テルミサルタンはPPARγを介して血管平滑筋細胞のアンジオテンシンIIタイプ1受容体の発現を抑制する2007

    • Author(s)
      市来 俊弘、砂川 賢二
    • Organizer
      第55回日本心臓病学会
    • Place of Presentation
      東京
    • Year and Date
      2007-09-10
    • Related Report
      2007 Annual Research Report
  • [Presentation] Resverarol downregualtes angioensin II type 1 receptor through activation of SIRT12007

    • Author(s)
      Miyazaki R, Ichik T, Inanaga K, Imayama I, Sunagawa K
    • Organizer
      61th Annual High Blood Pressure Research Conference
    • Place of Presentation
      USA
    • Related Report
      2008 Final Research Report
  • [Presentation] Inducible cAMP early repressor inhibits growth of vascular smooth muscle cells2007

    • Author(s)
      Ohtsubo H, Ichiki T, Sadoshima J, Sunagawa K
    • Organizer
      AHA Scientific Sessions 2007
    • Place of Presentation
      USA
    • Related Report
      2008 Final Research Report
  • [Presentation] A novel anti- inflammatory effect of resveratrolthrough suppression of AngiotensinII- induced Hypertension and Interleukin- 6 production. Circ J 20092007

    • Author(s)
      Inanaga K, Ichiki T, Takeda K, Myazaki R, Hashimoto T, Matsuura H, Sunagawa K
    • Organizer
      第73回日本循環器学会(73:392)
    • Place of Presentation
      大阪
    • Related Report
      2008 Final Research Report
  • [Presentation] Prolyl hydroxylase inhibitors attenuated acute inflammatory responses hypoxia- inducible factor independent manner. Circ J 20092007

    • Author(s)
      Takeda K, Ichiki T, Inanaga K, Hashimoto T, Matsuura H, Myazaki R, Sunagawa K
    • Organizer
      第73回日本循環器学会(73:218)
    • Place of Presentation
      大阪
    • Related Report
      2008 Final Research Report
  • [Presentation] Cholinergic Stimulation by Donepezil is a Novel Antiangiogenic approach. Circ J 20092007

    • Author(s)
      Myazaki R, Ichiki T, Takeda K, Inanaga K, Hashimoto T, Matsuura H, Sunagawa K
    • Organizer
      第73回日本循環器学会(73:627)
    • Place of Presentation
      大阪
    • Related Report
      2008 Final Research Report
  • [Presentation] Hashimoto T, Matsuura H, Sunagawa K. Cholinergic stimulation by donepezil as a novel antiatherosclerotic treatment. Circ J 20092007

    • Author(s)
      Inanaga K, Ichiki T, Takeda K, Myazaki R
    • Organizer
      第73回日本循環器学会(73:715)
    • Place of Presentation
      大阪
    • Related Report
      2008 Final Research Report

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Published: 2007-04-01   Modified: 2016-04-21  

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