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Vascular calcification by restoring Gas6-Axl survival pathway

Research Project

Project/Area Number 19590854
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionThe University of Tokyo

Principal Investigator

IIJIMA Katsuya  The University of Tokyo, 医学部・附属病院, 講師 (00334384)

Co-Investigator(Kenkyū-buntansha) OHIKE Yumiko  東京大学, 医学部・附属病院, 助教 (20359615)
OUCHI Yasuyoshi  東京大学, 医学部・附属病院, 教授 (80168864)
OGAWA Sumito  東京大学, 医学部・附属病院, 講師 (20323579)
Co-Investigator(Renkei-kenkyūsha) AKISHITA Masahiro  東京大学, 医学部・附属病院, 准教授 (00261975)
ETO Masato  東京大学, 医学部・附属病院, 講師 (80282630)
OTA Hidetaka  東京大学, 医学部・附属病院, 医員 (20431869)
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: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2007: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Keywords血管石灰化 / 高リン血症 / アポトーシス / Gas6-Axl / 細胞アポトーシス / Gas6-x1 / Gas6-Axl経路
Research Abstract

2年間の検討において、下記について明らかにした。
(1) 心血管石灰化におけるアディポサイトカインの役割の解明 TNF-αは高リン刺激による血管平滑筋細胞石灰化を促進し、その機序はリン刺激によりアポトーシスがTNF-αで増加し、Gas6-Axl survival pathway が抑制されることによる。(2)腎不全ラットモデルでの大動脈石灰化における新しい制御法・治療法の開発 大動脈におけるメンケベルグ型血管中膜石灰化モデル動物を作成した。水溶性スタチンおよびアンジオテンシンIIタイプ1 受容体阻害薬は大動脈石灰化を濃度依存的に抑制した。(3)腎機能と大動脈石灰化の相関および心血管イベント発症に関する臨床的検討 胸部X 線上の大動脈弓石灰化(AAC)の石灰化をグレード分類した。AAC グレードは、危険因子の重積により有意に増加した。(4)血管石灰化における性ホルモンの作用 高リン刺激による血管平滑筋細胞石灰化は女性ホルモン・男性ホルモン投与により濃度依存的に抑制され、アポトーシスも抑制された。

Report

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

    (47 results)

All 2009 2008 2007 Other

All Journal Article (17 results) (of which Peer Reviewed: 17 results) Presentation (27 results) Book (3 results)

  • [Journal Article] Validity and usefulness of aorticarch calcification in chest X-ray2009

    • Author(s)
      Hashimoto H, Iijima K, Hashimoto M, SonBK, Ota H, Ogawa S, Eto M, Akishita M, Ouchi Y.
    • Journal Title

      J Atheroscler Thromb (in press)

    • NAID

      10025765733

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Mechanism of pi-induced vascularcal cification2008

    • Author(s)
      Son BK, Akishita M, Iijima K, Eto M, Ouchi Y.
    • Journal Title

      J Atheroscler Thromb 15(2)

      Pages: 63-8

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Adiponectinantagonizes stimulatory effect of tumornecrosis factor-alpha on vascular smoothmuscle cell calcification2008

    • Author(s)
      Son BK, Akishita M, Iijima K, Kozaki K,Maemura K, Eto M, Ouchi Y.
    • Journal Title

      regulation of growtharrest-specific gene 6-mediated survivalpathway by adenosine5'-monophosphate-activated protein kinase.Endocrinology 149(4)

      Pages: 1646-53

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Nocturia in elderly people withhypertension--no influence of low-dosethiazide added to losartan2008

    • Author(s)
      Kojima T, Akishita M, Iijima K, Eto M, Ouchi Y.
    • Journal Title

      J Am Geriatr Soc 56(11)

      Pages: 2155-6

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Association ofplasma dehydroepiandrosterone-sulfate levelswith endothelial function in postmenopausalwomen with coronary risk factors2008

    • Author(s)
      Akishita M, Hashimoto M, Ohike Y, Ogawa S,Iijima K, Eto M, Ouchi Y.
    • Journal Title

      Hypertens Res 31(1)

      Pages: 69-74

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cilostazol inhibitsoxidative stress-induced premature senescencevia upregulation of Sirt1 in human endothelialcells2008

    • Author(s)
      Ota H, Eto M, Kano MR, Ogawa S, Iijima K,Akishita M, Ouchi Y.
    • Journal Title

      Arterioscler Thromb Vasc Biol 28(9)

      Pages: 1634-9

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Validity and usefulness of aortic arch calcification in chest X-ray.2008

    • Author(s)
      Hashimoto H, Iijima K, Hashimoto M, Son BK, Ota H, Ogawa S, Eto M, Akishita M, Ouchi Y.
    • Journal Title

      J Atheroscler Thromb. (in press)

    • NAID

      10025765733

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Adiponectin antagonizes stimulatory effect of TNF{alpha} on vascular smooth muscle cell calcification: Regulation of Gas6-mediated survival pathway by AMP-activated protein kinase.2008

    • Author(s)
      Son BK,Akishita M,lijima K,Kozaki K, Maemura K,Eto M,Ouchi Y.
    • Journal Title

      Endocrinology. 149

      Pages: 1646-1653

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mechanism of Pi-induced Vascular Calcification.2008

    • Author(s)
      Son BK,Akishita M,lijima K, Eto M,Ouchi Y.
    • Journal Title

      J Atheroscler Thromb. 15

      Pages: 63-68

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Adiponectin antagonizes stimulatory effect of TNF {alpha} on vascular smooth muscle cell calcification: Regulation of Gas6-mediated survival pathway by AMP-activated protein kinase.2008

    • Author(s)
      Son BK, Akishita M, lijima K, Kozaki K, Maemura K, Eto M, Ouchi Y.
    • Journal Title

      Endocrinology. 149

      Pages: 1646-53

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mechanism of Pi-Induced vasacular calcificatin.2008

    • Author(s)
      Son BK, Akishita M, lijima K, Eto M, Ouchi Y.
    • Journal Title

      J Atheroscler Thromb. (掲載確定)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Gas6/Axl-PI, 3K/Aktpathway plays a central role in the effect ofstatins on inorganic phosphate-inducedcalcification of vascular smooth muscle cells2007

    • Author(s)
      Son BK, Kozaki K, Iijima K, Eto M, Nakano T, Akishita M, Ouchi Y.
    • Journal Title

      Eur J Pharmacol 556

      Pages: 1-8

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Low testosteronelevel is an independent determinant ofendothelial dysfunction in men2007

    • Author(s)
      Akishita M, Hashimoto M, Ohike Y, OgawaS, Iijima K, Eto M, Ouchi Y.
    • Journal Title

      Hypertens Res 30(11)

      Pages: 1029-34

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Sirt1 modulates prematuresenescence-like phenotype in humanendothelial cells2007

    • Author(s)
      Ota H, Akishita M, Eto M, Iijima K, KanekiM, Ouchi Y.
    • Journal Title

      J Mol Cell Cardiol 43(5)

      Pages: 571-9

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Tako-tsubo-like left ventriculardysfunction in a patient with chronic totalocclusion of the left anterior descending artery2007

    • Author(s)
      Kojima T, Ako J, Eto M, Iijima K, AkishitaM, Ouchi Y.
    • Journal Title

      Int J Cardiol 119(1)

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Gas6/Axl-Pl3K/Akt pathway plays a central role in the effect of statins on inorganic phosphate-induced calcification of vascular smooth musclece cells2007

    • Author(s)
      Son BK, Kozaki K, lijima K, EtoM, Nakano T, Akishita M, Ouchi Y.
    • Journal Title

      Eur J Pharmacol. 556

      Pages: 1-8

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sirolimus andEverolimus induce endothelial cellularsenescence via sirt1 downregulation : Therapeutic implication of Cilostazol afterdrug-eluting stent implantation

    • Author(s)
      Ota H, Eto M, Ako J, Ogawa S, Iijima K,Akishita M, Ouchi Y.
    • Journal Title

      J Am Coll Cardiol (in press)

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Presentation] 大動脈弓石灰化の評価による心血管イベントの予測慢性腎臓病CKDとの関連2008

    • Author(s)
      飯島勝矢, 橋本寛子, 江頭正人, 大田秀隆, 野村和志, 山田容子, 秋下雅弘, 大内尉義
    • Organizer
      第50回日本老年医学会学術集会
    • Place of Presentation
      幕張
    • Related Report
      2008 Final Research Report
  • [Presentation] 高齢者糖尿病患者におけるメタボリック・シンドロームは摂取カロリーよりもPhysical activity(生活活動強度)の低下が大きく関与す2008

    • Author(s)
      飯島勝矢, 飯室聡, 大橋靖雄, 櫻井孝, 荒木厚, 大内尉義, 井藤英喜
    • Organizer
      第50回日本老年医学会学術集会
    • Place of Presentation
      幕張
    • Related Report
      2008 Final Research Report
  • [Presentation] ヒト血管内皮細胞におけるNO産生増加による細胞老化抑制機構2008

    • Author(s)
      大田秀隆, 江頭正人, 小川純人, 飯島勝矢,秋下雅弘, 大内尉義
    • Organizer
      第50回日本老年医学会学術集会
    • Place of Presentation
      幕張
    • Related Report
      2008 Final Research Report
  • [Presentation] 脂肪細胞に異所性に発現するeNOSは脂肪分解に対し抑制的にはたらく2008

    • Author(s)
      山田容子, 江頭正人, 伊藤友紀, 野村和至,大田秀隆, 孫輔卿, 小川純人, 飯島勝矢, 秋下雅弘, 大内尉義
    • Organizer
      第40回日本動脈硬化学会学術集会
    • Place of Presentation
      つくば
    • Related Report
      2008 Final Research Report
  • [Presentation] ヒト血管内皮細胞におけるNO産生増加薬剤による細胞老化抑制機構2008

    • Author(s)
      大田秀隆, 江頭正人, 小川純人, 飯島勝矢, 秋下雅弘, 大内尉義
    • Place of Presentation
      つくば
    • Related Report
      2008 Final Research Report
  • [Presentation] 胸部単純X 線における大動脈弓石灰化はどこまで心血管イベント発症に対する強い予測因子になりうるのか?2008

    • Author(s)
      飯島勝矢, 橋本寛子, 橋本正良, 小川純人, 江頭正人, 秋下雅弘, 大内尉義
    • 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] 血清テストステロン低値は血管内皮機能とは独立して中高年男性患者の心血管イベントに関連す2008

    • Author(s)
      秋下雅弘, 橋本正良, 小島太郎, 飯島勝矢,江頭正人, 大内尉義
    • 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] 高齢女性における内臓脂肪増加および全身筋肉量低下とメタボリックシンドローム構成因子の重複に関する横断研究2008

    • Author(s)
      野村和至, 江頭正人, 中村哲郎, 小島太郎,小川純人, 飯島勝矢, 荒木厚, 秋下雅弘, 大内尉義
    • Organizer
      第51回日本糖尿病学会年次学術集会
    • Place of Presentation
      東京
    • Related Report
      2008 Final Research Report
  • [Presentation] Vascular calcification as therapeutic in CKD patients2008

    • Author(s)
      秋下雅弘、飯島勝矢、大内尉義
    • Organizer
      第72回日本循環器学会学術集会
    • Place of Presentation
      福岡
    • Related Report
      2008 Final Research Report
  • [Presentation] Nitric oxide blocksoxidative stress induced premature endothelialsenescence by the longevity gene, Sirt 12008

    • Author(s)
      大田秀隆、江頭正人、小川純人、飯島勝矢、秋下雅弘、大内尉義
    • Organizer
      第72回日本循環器学会学術集会
    • Place of Presentation
      福岡
    • Related Report
      2008 Final Research Report
  • [Presentation] 大動脈弓石灰化の評価による心血管イベントの予測 慢性腎臓病CKDとの関連.2008

    • Author(s)
      飯島勝矢,橋本寛子,江頭正人,大田秀隆,野村和志,山田容子,秋下雅弘,大内尉義.
    • Organizer
      第50回日本老年医学会学術集会
    • Place of Presentation
      幕張
    • Related Report
      2008 Annual Research Report
  • [Presentation] 慢性腎臓病CKDにおける心血管石灰化2007

    • Author(s)
      飯島勝矢, 孫輔卿, 伊藤友紀, 江頭正人, 大池裕美子, 小島太郎, 大田秀隆, 野村和至, 秋下雅弘, 大内尉義
    • Organizer
      第39回日本動脈硬化学会総会
    • Place of Presentation
      大阪
    • Year and Date
      2007-07-13
    • Related Report
      2007 Annual Research Report
  • [Presentation] <Symposium> Atherosclerosisin the elderly-from the view of vascular celldysfunction Effects of statins oncardiovascular disease in the elderly : Possiblerole of vascular calcification2007

    • Author(s)
      Iijima K.
    • Organizer
      The 8thAsia/Oceania Regional Congress ofGerontology and Geriatrics
    • Place of Presentation
      Beijing
    • Related Report
      2008 Final Research Report
  • [Presentation] The associationof polypharmacy and hypertension with fallrisks among the elderly patients2007

    • Author(s)
      Kojima T, Akishita M, Yamaguchi K, OhikeY, Iijima K, Eto M, Ouchi Y.
    • Organizer
      The 8thAsia/Oceania Regional Congress ofGerontology and Geriatrics
    • Place of Presentation
      Beijing
    • Related Report
      2008 Final Research Report
  • [Presentation] Cilostazol, A selective inhibitor ofPDE3, Increases Resistance Against OxidativeStress-induced premature senescence inhuman endothelial cells2007

    • Author(s)
      Ota H, Eto M, Ogawa S, Iijima K, AkishitaM Ouchi Y.
    • Organizer
      The 8th Asia/OceaniaRegional Congress of Gerontology andGeriatrics
    • Place of Presentation
      Beijing
    • Related Report
      2008 Final Research Report
  • [Presentation] Obstructivesleep apnea exacerbates endothelialdysfunction in patients with metabolicsyndrome2007

    • Author(s)
      Akishita M, Ohike Y, Hashimoto M, Iijima K,Eto M, Teramoto S, Ouchi Y.
    • Organizer
      Scientific Sessions of AmericanHeart Association, Orlando
    • Place of Presentation
      USA
    • Related Report
      2008 Final Research Report
  • [Presentation] Blockade of Angiotensin II receptorenhances the inhibitory effect of statin onvascular calcification in renal failure rats2007

    • Author(s)
      Iijima K, Ito Y, Son BK, Eto M, Ogawa S Ota H, Nomura K, Yamada Y, Akishita M, Ouchi Y.
    • Organizer
      Scientific Sessions of American HeartAssociation, Orlando
    • Place of Presentation
      USA
    • Related Report
      2008 Final Research Report
  • [Presentation] Angiotensin-II receptorblocker enhances the inhibitory effect ofstatins on vascular calcification in uremic ratsinduced by adenine diet2007

    • Author(s)
      飯島勝矢、伊藤友紀、孫輔卿、江頭正人、小川純人、大池由美子、小島太郎、大田秀隆、野村和至、橋本寛子、山田容子、秋下雅弘、大内尉義
    • Organizer
      第71回日本循環器学会総会・学術集会
    • Place of Presentation
      神戸
    • Related Report
      2008 Final Research Report
  • [Presentation] Adiponectinantagonizes the stimulatory effect of TNF alfaon vascular smooth muscle cell calcification2007

    • Author(s)
      孫輔卿、飯島勝矢、神崎恒一、江頭正人、前村浩二、秋下雅弘、大内尉義
    • Organizer
      第71回日本循環器学会総会・学術集会
    • Place of Presentation
      神戸
    • Related Report
      2008 Final Research Report
  • [Presentation] Cilostazol, a selectiveinhibitor of PDE3, blocked oxidativestress-induced premature senescence ofhuman endothelial cells2007

    • Author(s)
      大田秀隆、江頭正人、向田修、飯島勝矢、秋下雅弘、大内尉義
    • Organizer
      第71回日本循環器学会総会・学術集会
    • Place of Presentation
      神戸
    • Related Report
      2008 Final Research Report
  • [Presentation] 高齢者の動脈硬化危険因子の重複に内臓脂肪が及ぼす影響に関する臨床研究2007

    • Author(s)
      野村和至, 秋下雅弘, 中村哲郎, 山田優子, 小島太郎, 大池裕美子, 飯島勝矢, 荒木厚, 江頭正人, 大内尉義
    • Organizer
      第104回日本内科学会総会・講演会
    • Place of Presentation
      大阪
    • Related Report
      2008 Final Research Report
  • [Presentation] <シンポジウム : 慢性腎臓病CKDと動脈硬化> 慢性腎臓病CKDにおける心血管石灰化2007

    • Author(s)
      飯島勝矢
    • Organizer
      第39回日本動脈硬化学会総会
    • Place of Presentation
      大阪
    • Related Report
      2008 Final Research Report
  • [Presentation] 血管細胞老化と動脈硬化PDE3阻害薬、シロスタゾールによる血管内皮premature senescence 抑制作用メカニズム2007

    • Author(s)
      大田秀隆, 江頭正人, 飯島勝矢, 秋下雅弘, 大内尉義
    • Organizer
      第39回日本動脈硬化学会総会
    • Place of Presentation
      大阪
    • Related Report
      2008 Final Research Report
  • [Presentation] 血管平滑筋細胞の石灰化に対するTNFαの促進作用及びadiponectinの拮抗作用2007

    • Author(s)
      孫輔卿, 飯島勝矢, 江頭正人, 秋下雅弘,大内尉義
    • Organizer
      第39回日本動脈硬化学会総会
    • Place of Presentation
      大阪
    • Related Report
      2008 Final Research Report
  • [Presentation] 高齢者の腹部大動脈石灰化と腎機能障害との関連についての検討2007

    • Author(s)
      野村和至, 秋下雅弘, 中村哲郎, 小島太郎, 大池裕美子, 飯島勝矢, 江頭正人, 大内尉義
    • Organizer
      第39回日本動脈硬化学会総会
    • Place of Presentation
      大阪
    • Related Report
      2008 Final Research Report
  • [Presentation] SIRT1阻害によるヒト血管平滑筋細胞増殖抑制と細胞老化形質誘導2007

    • Author(s)
      小林貴、大田秀隆、小川純人、飯島勝矢、江頭正人、秋下雅弘、金木正夫、大内尉義
    • Organizer
      第39回日本動脈硬化学会総会
    • Place of Presentation
      大阪
    • Related Report
      2008 Final Research Report
  • [Presentation] PDE3阻害薬、シロスタゾールによるヒト血管内皮細胞のpremature senescence抑制機構2007

    • Author(s)
      大田秀隆、江頭正人、向田修、小川純人、飯島勝矢、秋下雅弘、大内尉義
    • Organizer
      第49回日本老年医学会学術集会
    • Place of Presentation
      札幌
    • Related Report
      2008 Final Research Report
  • [Book] 慢性臓器不全の管理の方策 1.慢性心不全.(葛谷雅文、秋下雅弘編 : ベッドサイドの高齢者の診かた)2008

    • Author(s)
      飯島勝矢
    • Publisher
      南山堂・東京
    • Related Report
      2008 Final Research Report
  • [Book] 急性期状態の高齢者の特徴・鑑別・介入 9.呼吸困難.(葛谷雅文、秋下雅弘編 : ベッドサイドの高齢者の診かた)2008

    • Author(s)
      飯島勝矢
    • Publisher
      南山堂・東京
    • Related Report
      2008 Final Research Report
  • [Book] ベッドサイドの高齢者の診かた2008

    • Author(s)
      飯島勝矢
    • Total Pages
      340
    • Publisher
      南山堂・東京
    • Related Report
      2008 Annual Research Report

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

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