Ion channel-mediated blood flow-sensing mechanism in vascular endothelial cells

• Project/Area Number: 18200030
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Biomedical engineering/Biological material science
• Research Institution: The University of Tokyo
• Principal Investigator: ANDO Joji The University of Tokyo, 大学院・医学系研究科, 教授 (20159528)
• Co-Investigator(Kenkyū-buntansha): YAMAMOTO Kimiko 東京大学, 大学院・医学系研究科, 講師 (00323618)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥48,880,000 (Direct Cost: ¥37,600,000、Indirect Cost: ¥11,280,000); Fiscal Year 2008: ¥12,220,000 (Direct Cost: ¥9,400,000、Indirect Cost: ¥2,820,000); Fiscal Year 2007: ¥12,220,000 (Direct Cost: ¥9,400,000、Indirect Cost: ¥2,820,000); Fiscal Year 2006: ¥24,440,000 (Direct Cost: ¥18,800,000、Indirect Cost: ¥5,640,000)
• Keywords: カルシウムイオン / 剪断応力 / ATP受容体 / 細胞膜 / 遺伝子欠損マウス / 血管 / 血流 / 伸展張力 / 内皮細胞 / エンドセリン / NO合成酵素 / カルシウム・イオン / ATP / ATP合成酵素 / 遺伝子血管マウス

Research Abstract

血流による血管の働きの調節は血管内皮細胞が血流に起因する力学的刺激である剪断応力を感知して応答する事に基づいている。我々は内皮細胞の剪断応力感知機構に細胞膜に分布するATP作動性イオンチャネルP2X4を介する細胞外カルシウムの流入反応が重要な役割を果たすことを明らかにしてきた。本研究により剪断応力の強さ依存性に放出されるATPがP2X4を活性化すること、剪断応力によるATP放出に細胞膜カベオラにあるATP合成酵素が関与することが判明し、血流の情報が細胞内部に伝達される血流センシングの分子機構の解明が進んだ。

Research Products

• [Journal Article] Fluid shear stress induces arterial differentiation of endothelial progenitor cells (2009)
  • Author(s): S. Obi, K. Yamamoto, N. Shimizu, S. Kumagaya, T. Masumura, T. Sokabe, T. Asahara, and J. Ando
  • Journal Title: J. Appl. Physiol 106 Pages: 203-211
  • Peer Reviewed
• [Journal Article] Fluid shear stress induces arterial differentiation of endothelial progenitor cells (2009)
  • Author(s): S. Obi, J. Ando, et al
  • Journal Title: J. Appl. Physiol. 106 Pages: 203-211
  • Peer Reviewed
• [Journal Article] Cyclic strain induces mouse embryonic stem cell differentiation into vascular smooth muscle cells by activating PDGF receptor b (2008)
  • Author(s): N. Shimizu, K. Yamamoto, S. Obi, S. Kumagaya, T. Masumura, Y. Shimano, K. Naruse, J.K. Yamashita, T. Igarashi, and J. Ando
  • Journal Title: J. Appl. Physiol 104 Pages: 766-772
  • Peer Reviewed
• [Journal Article] Differential gene responses in endothelial cells exposed to a combination of shear stress and cyclic stretch (2008)
  • Author(s): M. Toda, K. Yamamoto, N Shimizu, S. Obi, S. Kumagaya, T. Igarashi, A. Kamiya, and J. Ando
  • Journal Title: J. Biothechnol 133 Pages: 239-244
  • Peer Reviewed
• [Journal Article] Cyclic strain induces mouse embryonic stem cell differentiaiion into vascular smooth muscle cells by activating PDGF receptor b (2008)
  • Author(s): N. Shimizu, J. Ando, et al
  • Journal Title: J. Appl. Physiol. 104 Pages: 766-772
  • Peer Reviewed
• [Journal Article] Fibronectin/integrin system is involved in P2X4 receptor upregulation in the spinal cord and neuropathic pain after nerve injury (2008)
  • Author(s): M. Tsuda, J. Ando, et al
  • Journal Title: Glia 56 Pages: 579-585
  • Peer Reviewed
• [Journal Article] Differental gene responses in endothelial cells exposed to a combination of shear stress and cyclic stretch (2008)
  • Author(s): M. Toda, J. Ando, et al
  • Journal Title: J. Biothechnol. 133 Pages: 239-244
  • Peer Reviewed
• [Journal Article] 力学的刺激による幹細胞・前駆細胞の血管細胞への分化誘導 生体医工学 (2008)
  • Author(s): 安藤譲二、山本希美子
  • Journal Title: 生体医工学会誌 46 Pages: 419-424
• [Journal Article] P2X4欠損マウスとシェアストレスのセンシング 血栓と循環 (2008)
  • Author(s): 山本希美子、安藤譲二
  • Journal Title: 日本バイオレオロジー学会誌 16 Pages: 4-8
• [Journal Article] Cyclic strain induces mouse embryonic stem cell differentiation into vascular smoothmuscle cells by activating PDGF receptor (2008)
  • Author(s): N.Shimizu, J.Ando, et. al.
  • Journal Title: J.Appl Physiol 104 Pages: 766-772
  • Peer Reviewed
• [Journal Article] Fibronectin/integrin system is involved in P2×4receptor upregulation in the spinal cord and neuropathic pain after nerve injury (2008)
  • Author(s): M.Tsuda, J.Ando, et. al.
  • Journal Title: Glia 56 Pages: 579-585
  • Peer Reviewed
• [Journal Article] Differential gene responses in endothelial cells exposed to a combination of shear stress and cyclic stretch (2008)
  • Author(s): M.Toda, J.Ando, et. al.
  • Journal Title: J.Biothechnol 133 Pages: 239-244
  • Peer Reviewed
• [Journal Article] Involvement of cell surface ATP synthase in flow-induced ATP release by vascular endothelial cells (2007)
  • Author(s): K. Yamamoto, N. Shimizu, S. Obi, S. Kumagaya, Y. Taketani, A. Kamiya, and J. Ando
  • Journal Title: Am. J. Physiol Heart Circ. Physiol 293
  • Peer Reviewed
• [Journal Article] Involvement of cell surface ATP synthase in flow-induced ATP release by vascularendothelial cells (2007)
  • Author(s): K.Yamamoto, J.Ando, et. al.
  • Journal Title: Am.J.Physiol Heart Circ.Physiol 293
  • Peer Reviewed
• [Journal Article] Multipysics simulation of blood flow and LDL transport in aporohyperelastic arterial wall model (2007)
  • Author(s): N.Koshiba, J.Ando, X.Chen, and T.Hisada
  • Journal Title: J.Biomech.Eng 129 Pages: 374-385
  • Peer Reviewed
• [Journal Article] Development of an in vivo tissue-engineered,autologous heart valve 9the biovalve):Preparation of a prototype model (2007)
  • Author(s): K.Hayashida, K.Kanda, H.Yaku, J.Ando, Y.Nakayama
  • Journal Title: J.Throac.Cardiovasc.Surg 134 Pages: 152-159
  • Peer Reviewed
• [Journal Article] Adequate design of customized cDNA microarray for convention multiple gene expression analysis. (2007)
  • Author(s): S.Sugiyama, K.Yamamoto, N.Nishimura, M.Nakagawa, Y.Maruta, J.Ando
  • Journal Title: J. Biosci. Bioeng. 103 Pages: 74-81
• [Journal Article] Impaired flow-dependent control of vascular tone and remodeling in P2X4-deficient mice (2006)
  • Author(s): K. Yamamoto, T. Sokabe, T. Matsumoto, K. Yoshimura, M. Shibata, N. Ohura, T. Fukuda, K. Sekine, S. Kato, M. Isshiki, T. Fujita, M. Kobayashi, K. Kawamura, H. Masuda, A. Kamiya, and J. Ando
  • Journal Title: Nat. Med 12 Pages: 133-137
  • Peer Reviewed
• [Journal Article] Shear stress induces hepatocyte PAI-1 gene expression thorugh cooperative Sp1/Ets-1 activation of transcription. (2006)
  • Author(s): H.Nakatsuka, T.Sokabe, K.yamamoto, Y.Sato, K.Hatakeyama, A.Kamiya, J.Ando
  • Journal Title: Am. J. Phsyiol. Gastrointest. Liver Physiol 291
• [Journal Article] Phenotypic responses to mechanical stress in fibroblasts from tendon, cornea and skin (2006)
  • Author(s): J.R.Macklley, J.Ando, P.Herzyk, S, J.Winder
  • Journal Title: Biochem. J. 396 Pages: 307-316
• [Journal Article] Cell-surface-localized ATP detection with immobilized firefly luciferase. (2006)
  • Author(s): M.Nakamura, M.Mie, H.Funabashi, K.Yamamoto, J.Ando
  • Journal Title: Anal. Biochem. 352 Pages: 61-67
• [Journal Article] Impaired flow-dependent control of vascular tone and remodeling in P2X4-deficient mice. (2006)
  • Author(s): K.Yamamoto, T.Sokabe, T.Matsumoto, K.Yoshimura, M.Shibata, N.Ohura, T.Kamiya, J.Ando at al.
  • Journal Title: Nat. Med. 12 Pages: 133-137
• [Journal Article] シェアストレスによる血管細胞の分化誘導 (2006)
  • Author(s): 山本希美子, 安藤譲二
  • Journal Title: 実験医学 24 Pages: 2817-2823
• [Presentation] 血流による血管トーヌスの調節 (2009)
  • Author(s): 安藤譲二
  • Organizer: 第38回日本心脈管作動物質学会
  • Place of Presentation: 岡山
  • Year and Date: 2009-02-06
• [Presentation] 血流による血管卜-タスの調節 (2009)
  • Author(s): 安藤譲二
  • Organizer: 第38回日本心脈管作動物質学会
  • Place of Presentation: 岡山市 岡山大学創立五十周年記念館
  • Year and Date: 2009-02-06
• [Presentation] Shear-stress-sensing and response mechanisms in vascular endothelial cells (2009)
  • Author(s): J. Ando
  • Organizer: The 3rd International Symposium for Interface Oral Health Science
  • Place of Presentation: Sendai, Japan
  • Year and Date: 2009-01-15
• [Presentation] Shear-stress-sensing and response mechanisms in vascular endothelial cells (2009)
  • Author(s): J. Ando and K. Yamamoto
  • Organizer: The 3rd International Symposium for Interface Oral Health Science
  • Place of Presentation: 仙台市 仙台国際センター
  • Year and Date: 2009-01-15
• [Presentation] Shear-stress-mediated endothelial signaling and vascular homeostasis (2008)
  • Author(s): J. Ando
  • Organizer: The 13th International Conference on Biomedical Engineering
  • Place of Presentation: Singapore
  • Year and Date: 2008-12-05
• [Presentation] Shear-stress-mediated endothelial signalig and vascular homeostasis (2008)
  • Author(s): J. Ando and K. Yamamoto
  • Organizer: The 13th International Conference on Biomedical Engineering
  • Place of Presentation: Suntec City, Singapore
  • Year and Date: 2008-12-05
• [Presentation] Cyclic strain induces ES cell differentiation into vascular smooth muscle cell via PDGF receptor b activation (2008)
  • Author(s): K. Yamamoto, N. Shimjzu, S. Obi and J. Ando
  • Organizer: 2008 International Symposium on Micro-NaoMechantronics and Human Science
  • Place of Presentation: 名古屋市 名古屋大学野依学術記念交流館
  • Year and Date: 2008-11-08
• [Presentation] Cyclic strain induces mouse embryonic stem cell differentiation into vascular smooth muscle cells (2008)
  • Author(s): J. Ando
  • Organizer: 2008 BMES Annual Fall Meeting
  • Place of Presentation: St. Louis, USA
  • Year and Date: 2008-10-02
• [Presentation] Induction of vascular cell differentiation by fluid-mechanical forces in embryonic stem cells (2008)
  • Author(s): J. Ando
  • Organizer: ISACB 11th Biennial Meeting
  • Place of Presentation: Bordeaux, France
  • Year and Date: 2008-09-19
• [Presentation] Induction of vascular cell differentiation by fluid-mechanical forces in embryonic stem cells (2008)
  • Author(s): J. Ando, K. Yamamoto and N. Shimizu
  • Organizer: ISACB 11th Biennial Meetig
  • Place of Presentation: Bordeaux, France
  • Year and Date: 2008-09-19
• [Presentation] 流れ剪断応力はES細胞においてNotchリガンドDl14を増加させる (2008)
  • Author(s): 桝村智美、安藤譲二, 他
  • Organizer: 第47回日本生体医工学学会
  • Place of Presentation: 神戸市 神戸国際会議場
  • Year and Date: 2008-05-09
• [Presentation] マウス胚性幹細胞の動静脈分化に及ぼす流れずり応力の効果 (2008)
  • Author(s): 清水信隆、安藤譲二, 他
  • Organizer: 第47回日本生体医工学学会
  • Place of Presentation: 神戸市 神戸国際会議場
  • Year and Date: 2008-05-08
• [Presentation] 流れずり応力は内皮前駆細胞においてephrinB2遺伝子の転写を増加させる (2008)
  • Author(s): 小尾正太郎、安藤譲二, 他
  • Organizer: 第47回日本生体医工学学会
  • Place of Presentation: 神戸市 神戸国際会議場
  • Year and Date: 2008-05-08
• [Presentation] 二光子顕微鏡による血管内皮細胞の膜脂質ミクロドメインの動態観察 (2008)
  • Author(s): 山本希美子、安藤譲二, 他
  • Organizer: 第47回日本生体医工学学会
  • Place of Presentation: 神戸市 神戸国際会議場
  • Year and Date: 2008-05-08
• [Presentation] 血管内皮細胞における流れ剪断応力依存性ATP放出の画像化 (2008)
  • Author(s): 山本希美子、安藤譲二, 他
  • Organizer: 第47回日本生体医工学学会
  • Place of Presentation: 神戸市 神戸国際会議場
  • Year and Date: 2008-05-08
• [Presentation] 細動脈における血流によるずり応力 (2008)
  • Author(s): 柴田政廣、市岡滋、安藤譲二、神谷瞭
  • Organizer: 第47回日本生体医工学学会
  • Place of Presentation: 神戸市 神戸国際会議場
  • Year and Date: 2008-05-08
• [Presentation] Blood-flow sensing by endothelial cells and its role in the regulation of circulatory system (2008)
  • Author(s): J. Ando (教育講演)
  • Organizer: 第33回日本微小循環学会
  • Place of Presentation: 東京
  • Year and Date: 2008-02-22
• [Presentation] Cell surface ATP synthasemediated shear stress mechanotransduction in vascular endothelial cells (2008)
  • Author(s): K. Yamamoto
  • Organizer: 16th IUPAB International Biophysics Congress
  • Place of Presentation: Long Beach, U.S.A
  • Year and Date: 2008-02-06
• [Presentation] Cell surface ATP synthase-mediated shear stress mechanotransduction in vascular endothelial cells (2008)
  • Author(s): K. Yamamoto, and J. Ando
  • Organizer: 16th IUPAB International Biophysics Congress
  • Place of Presentation: Long Beach,Caifbrnia
  • Year and Date: 2008-02-06
• [Presentation] 内皮細胞における血流刺激のメカノトランスダクション、シンポジウム「メカノバイオロジーの分子生物学」 (2007)
  • Author(s): 安藤譲二
  • Organizer: 第30回日本分子生物学会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-14
• [Presentation] 内皮細胞における血流刺激のメカノトランスダクション (2007)
  • Author(s): 安藤 譲二, 山本 希美子
  • Organizer: 第30回日本分子生物学会シンポジウム「メカノバイオロジーの分子生物学」
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-14
• [Presentation] 二光子レーザ顕微鏡による血管内皮細胞膜の脂質ラフトの画像化 (2007)
  • Author(s): 山本 希美子, 安藤 譲二, 他.
  • Organizer: 第15回日本血管生物医学会学術大会
  • Place of Presentation: 福岡
  • Year and Date: 2007-11-30
• [Presentation] Caveola ATP synthase mediates ATP release in vascular endothelial cells exposed to shear stress (2007)
  • Author(s): K. Yamamoto, S. Obi, N. Shimizu, S. Kumagaya, and J. Ando.
  • Organizer: International Symposium on Micro-NanoMechanics and Human Science
  • Place of Presentation: Nagoya,Japan
  • Year and Date: 2007-11-13
• [Presentation] 和舟漕ぎ型パワーアシスト・ウエルネス改善マシンの開発 (2007)
  • Author(s): 小林 寛道
  • Organizer: 日本体育学会第58回大会
  • Place of Presentation: 神戸大学
  • Year and Date: 2007-09-05
• [Presentation] 血流による血管構築・機能の制御と病態発生 (2007)
  • Author(s): 安藤譲二
  • Organizer: 第12回日本冠動脈外科学会学術総会 教育講演
  • Place of Presentation: 東京
  • Year and Date: 2007-07-15
• [Presentation] 血管内皮細胞における流れずり応力依存性ATP放出の分子機構 (2007)
  • Author(s): 山本 希美子, 熊谷 晋一郎, 安藤 譲二
  • Organizer: 第30回日本バイオレオロジー学会
  • Place of Presentation: 札幌
  • Year and Date: 2007-06-15
• [Presentation] 血管のメカノ・フィジオロジー (2007)
  • Author(s): 安藤 譲二
  • Organizer: 第20回Okayama Nephro-Talk
  • Place of Presentation: 岡山
  • Year and Date: 2007-06-13
• [Presentation] ATP受容体を介した血管内皮のメカノトランスダクション、専門別研究会「細胞バイオメカニクスの新展開 : 分子生物学的手法によるアプローチ」 (2007)
  • Author(s): 安藤譲二
  • Organizer: 第46回日本生体医工学学会
  • Place of Presentation: 仙台
  • Year and Date: 2007-04-26
• [Presentation] ATP受容体を介した血管内皮のメカノトランスダクション専門別研究会 細胞バイオメカニクスの新展開:分子生物学的手法によるアプローチ (2007)
  • Author(s): 安藤 譲二, 山本希 美子
  • Organizer: 第46回目本生体医工学学会
  • Place of Presentation: 仙台
  • Year and Date: 2007-04-26
• [Presentation] 血管のシアストレスセンサー、シンポジウム「感覚センサー : 物理的刺激センサーのセンシング機構と生理的意義」 (2007)
  • Author(s): 安藤譲二
  • Organizer: 第84回日本生理学会
  • Place of Presentation: 大坂
  • Year and Date: 2007-03-21
• [Presentation] シェアストレスと血管リモデリング、シンポジウム「血栓症 : Virchow Code」 (2006)
  • Author(s): 安藤譲二
  • Organizer: 第29回日本血栓止血学会
  • Place of Presentation: 宇都宮
  • Year and Date: 2006-11-18
• [Presentation] Fluid shear stress induces selective differentiation of Flk-1-positive embryonic stem cells (2006)
  • Author(s): K. Yamamoto
  • Organizer: World Congress on Medical Physics and Biomedical Engineering
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2006-08-28
• [Presentation] 血管細胞のバイオメカニクス (2006)
  • Author(s): 安藤譲二
  • Organizer: 第2回REDEEMシンポジウム 医療工学の最前線
  • Place of Presentation: 東京
  • Year and Date: 2006-08-12
• [Presentation] The role of endothelial P2X4 receptors in flow-dependent control of vascular tone and remodeling (2006)
  • Author(s): J. Ando
  • Organizer: 5th World Congress of Biomechanics
  • Place of Presentation: Munich, Germany
  • Year and Date: 2006-08-03
• [Book] 血管トーヌスとリモデリングAnnual Review循環器 (2008)
  • Author(s): 安藤 譲二, 山本 希美子
  • Publisher: 中外医学社
• [Book] 医学のあゆみ223巻 (2007)
  • Author(s): 安藤 譲二, 山本 希美子
  • Publisher: 医歯薬出版
• [Book] 医学のあゆみ221巻 (2007)
  • Author(s): 安藤 譲二, 山本 希美子
  • Publisher: 医歯薬出版
• [Book] 日本ロボット学会誌25巻 (2007)
  • Author(s): 安藤 譲二, 山本 希美子
  • Publisher: 日本ロボット学会
• [Book] 循環器科 (2006)
  • Author(s): 安藤譲二, 曾我部隆影, 山本希美子
  • Total Pages: 671
  • Publisher: 科学評論社