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

2008 Fiscal Year Final Research Report

• 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
• 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

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] 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] 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 Pages: H1646-H1653
  • Peer Reviewed
• [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
• [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] 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-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] 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] 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] 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] 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] 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] 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