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Mechanoresponses of endothelial cell membranes to fluid shear stress

Research Project

Project/Area Number 25282128
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Biomedical engineering/Biomaterial science and engineering
Research InstitutionThe University of Tokyo

Principal Investigator

Yamamoto Kimiko  東京大学, 医学(系)研究科(研究院), 講師 (00323618)

Co-Investigator(Kenkyū-buntansha) ANDO Joji  獨協医科大学, 医学部, 特任教授 (20159528)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥18,980,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥4,380,000)
Fiscal Year 2015: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2014: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2013: ¥9,880,000 (Direct Cost: ¥7,600,000、Indirect Cost: ¥2,280,000)
Keywords流れずり応力 / 血管内皮細胞 / 細胞膜 / コレステロール / 伸展張力 / メカノトランスダクション / メカノセンシング / 細胞増殖因子受容体 / カベオラ
Outline of Final Research Achievements

Vascular endothelial cells (ECs) respond to the hemodynamic shear stress and stretch by altering their morphology, functions, and gene expression. Here we conclude that plasma membranes differentiate between stretch and shear stress by undergoing transitions in their lipid phases. Shear stress decreased the lipid order of EC plasma membranes; stretching increased the membrane lipid order. Similar changes occurred in the artificial lipid bilayer membranes, indicating that these are physical phenomena. Blocking these changes in the membrane lipid order by depleting membrane cholesterol with MβCD or by adding cholesterol resulted in marked inhibitions of the stretch or shear stress induced phosphorylation of PDGF receptors or VEGF receptors, respectively. These results indicate that EC membranes differently respond to hemodynamic forces and that the changes in membrane physical properties are involved in the mechanotransduction that activates membrane receptors by each force.

Report

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

    (47 results)

All 2016 2015 2014 2013 Other

All Journal Article (9 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 9 results,  Acknowledgement Compliant: 5 results,  Open Access: 2 results) Presentation (32 results) (of which Int'l Joint Research: 2 results,  Invited: 23 results) Book (2 results) Remarks (4 results)

  • [Journal Article] Vascular endothelial cell membranes differentiate between stretch and shear stress through transitions in their lipid phases.2015

    • Author(s)
      K. Yamamoto and J. Ando
    • Journal Title

      Am. J. Physiol. Heart Circ. Physiol.

      Volume: 309 Issue: 7 Pages: H1178-H1185

    • DOI

      10.1152/ajpheart.00241.2015

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Phosphorylation of PACSIN2 by protein kinase C triggers the removal of caveolae from the plasma membrane.2015

    • Author(s)
      Senju Y, Rosenbaum E, Shah C, Hamada-Nakahara S, Itoh Y, Yamamoto K, Hanawa-Suetsugu K, Daumke O, Suetsugu S.
    • Journal Title

      J Cell Sci.

      Volume: 128 Pages: 2766-2780

    • DOI

      10.1242/jcs.167775

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Assessment of Myogenic Power Expenditure Due to Arterial Wall Smooth Muscle Contraction Based upon the Fractal Nature of Vascular Trees.2014

    • Author(s)
      A. Kamiya, M. Shibata, and K. Yamamoto
    • Journal Title

      Applied Mathematics

      Volume: 5 Issue: 12 Pages: 1750-1762

    • DOI

      10.4236/am.2014.512168

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Dextran induces differentiation of circulating endothelial progenitor cells.2014

    • Author(s)
      S. Obi, H. Masuda, H. Akimaru, T. Shizuno, K. Yamamoto, J. Ando, and T. Asahara
    • Journal Title

      Physiol. Rep.

      Volume: 2 Issue: 3 Pages: e00261-e00261

    • DOI

      10.1002/phy2.261

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Effects of shear stress on endothelial progenitor cells.2014

    • Author(s)
      S. Obi, K. Yamamoto, and J. Ando
    • Journal Title

      J. Biomed. Nanotechnol.

      Volume: 10 Issue: 10 Pages: 2586-2597

    • DOI

      10.1166/jbn.2014.2014

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Endothelial progenitor cells promote directional three-dimensional endothelial network formation by secreting vascular endothelial growth factor.2013

    • Author(s)
      Y. Abe, Y. Ozaki, J. Kasuya, K. Yamamoto, J. Ando, R. Sudo, M. Ikeda and K. Tanishita
    • Journal Title

      PLoS ONE

      Volume: 8(12) Issue: 12 Pages: 1-12

    • DOI

      10.1371/journal.pone.0082085

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Flow detection and calcium signaling in vascular endothelial cells.2013

    • Author(s)
      J. Ando and K. Yamamoto
    • Journal Title

      Cardiovasc. Res.

      Volume: 99 Issue: 2 Pages: 260-268

    • DOI

      10.1093/cvr/cvt084

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Endothelial cell and model membranes respond to shear stress by rapidly decreasing the order of their lipid phases.2013

    • Author(s)
      K. Yamamoto and J. Ando
    • Journal Title

      J. Cell Sci.

      Volume: 126 Issue: 5 Pages: 1227-1234

    • DOI

      10.1242/jcs.119628

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dynamic imaging of flow-induced endothelial cell responses2013

    • Author(s)
      山本希美子、安藤譲二
    • Journal Title

      Japanese Journal of Thrombosis and Hemostasis

      Volume: 24 Issue: 6 Pages: 569-575

    • DOI

      10.2491/jjsth.24.569

    • NAID

      130003393319

    • ISSN
      0915-7441, 1880-8808
    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Presentation] 血管のメカノバイオロジー2016

    • Author(s)
      山本希美子
    • Organizer
      超高速バイオアセンブラ第10回公開シンポジウム
    • Place of Presentation
      東京大学生産技術研究所 (東京都目黒区)
    • Year and Date
      2016-03-22
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Sustained expression of MCP-1 regardless changes in hemodynamic status during intracranial aneurysm formation/progression.2016

    • Author(s)
      Tomohiro Aoki, Kimiko Yamamoto, Miyuki Fukuda, Shuh Narumiya
    • Organizer
      第89回日本薬理学会年会
    • Place of Presentation
      パシフィコ横浜 (神奈川県横浜市)
    • Year and Date
      2016-03-10
    • Related Report
      2015 Annual Research Report
  • [Presentation] 血管のメカノバイオロジー 現在と未来2016

    • Author(s)
      山本希美子
    • Organizer
      九州大学大学院医学研究院 系統解剖学セミナー
    • Place of Presentation
      九州大学医学部 (福岡県福岡市)
    • Year and Date
      2016-02-05
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 内皮細胞形質膜を介した血流と血圧のセンシング機構2015

    • Author(s)
      山本希美子、安藤譲二
    • Organizer
      第23回日本血管生物医学会学術集会(心血管代謝週間2015)
    • Place of Presentation
      神戸国際会議場 (兵庫県神戸市)
    • Year and Date
      2015-12-11
    • Related Report
      2015 Annual Research Report
  • [Presentation] Endothelial cell plasma membranes act as a mechanosensor that detects fluid shear stress2015

    • Author(s)
      Kimiko Yamamoto and Joji Ando
    • Organizer
      10th World congress for Microcirculation
    • Place of Presentation
      Kyoto International Conference Center (京都府京都市)
    • Year and Date
      2015-09-24
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 内皮細胞形質膜を介した血流センシング機構2015

    • Author(s)
      山本希美子、安藤譲二
    • Organizer
      生理学研究所研究会 生体ホメオスタシスのgatewayとしての上皮膜輸送マイクロホメオスタシス機構
    • Place of Presentation
      自然科学研究機構 生理学研究所 (愛知県岡崎市)
    • Year and Date
      2015-09-16
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Stretch-induced endothelial mechanotransduction through transitions in cell membrane lipid phases2015

    • Author(s)
      Kimiko Yamamoto and Joji Ando
    • Organizer
      37th Annual International Conference of the IEEE Engineering in Medicine and Biology Society
    • Place of Presentation
      Milano Conference Center, Milano (Italy)
    • Year and Date
      2015-08-28
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 内皮細胞の血流センシングを介した血管機能調節2015

    • Author(s)
      安藤譲二、山本希美子
    • Organizer
      第47回日本動脈硬化学会総会・学術集会
    • Place of Presentation
      仙台国際センター (宮城県仙台市)
    • Year and Date
      2015-07-10
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 血流による機械的刺激に対するYAP1の応答機構2015

    • Author(s)
      中嶋洋行、山本希美子、福井一、福原茂朋、望月直樹
    • Organizer
      第67回日本細胞生物学会大会
    • Place of Presentation
      タワーホール船堀 (東京都江戸川区)
    • Year and Date
      2015-06-30
    • Related Report
      2015 Annual Research Report
  • [Presentation] 内皮細胞膜は流体力学刺激のセンサーとして働く (Vascular endothelial cell membranes act as mechanosensors of hemodynamic forces)2015

    • Author(s)
      山本希美子、安藤譲二
    • Organizer
      第54回日本生体医工学会大会
    • Place of Presentation
      名古屋国際会議場 (愛知県名古屋市)
    • Year and Date
      2015-05-08
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 血管のメカノバイオロジー (Vascular mechanobiology)2015

    • Author(s)
      安藤譲二、山本希美子
    • Organizer
      第118回日本小児科学会学術集会
    • Place of Presentation
      大阪国際会議場/リーガロイヤルホテル大阪 (大阪府大阪市)
    • Year and Date
      2015-04-18
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 内皮細胞における形質膜を介したメカノセンシング2014

    • Author(s)
      山本希美子
    • Organizer
      第59回Blood Vessel Club
    • Place of Presentation
      東京大学、東京
    • Year and Date
      2014-10-27
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Vascular endothelial cells sense shear stress by changing the membrane lipid order2014

    • Author(s)
      Kimiko Yamamoto and Joji Ando
    • Organizer
      The 4th Japan-Switzerland Workshop on Biomechanics (JSB2014)
    • Place of Presentation
      Shima Kanko Hotel The Classic, Mie
    • Year and Date
      2014-09-02
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Caveolar membrane lipid order affects ATP-mediated shear stress mechanotransduction in vascular endothelial cells2014

    • Author(s)
      Kimiko Yamamoto and Joji Ando
    • Organizer
      Purines 2014
    • Place of Presentation
      University of Bonn, Bonn, Germany
    • Year and Date
      2014-07-24
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 内皮細胞膜のlipid orderを介したshear stressのセンシング2014

    • Author(s)
      山本希美子、安藤譲二
    • Organizer
      第53回日本生体医工学会大会
    • Place of Presentation
      仙台国際センター、仙台
    • Year and Date
      2014-06-26
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Hemodynamic control of vascular remodeling through endothelial cell mechanotransduction2014

    • Author(s)
      Kimiko Yamamoto and Joji Ando
    • Organizer
      The 47th Annual Meeting of the Japanese Society of Developmental Biologists
    • Place of Presentation
      WINC Aichi, Nagoya
    • Year and Date
      2014-05-30
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Endothelial cells respond to shear stress by rapidly decreasing the order of their lipid phases2014

    • Author(s)
      Kimiko Yamamoto and Joji Ando
    • Organizer
      International Symposium on Mechanobiology (ISMB2014)
    • Place of Presentation
      Okayama University Junko Fukutake Hall, Okayama
    • Year and Date
      2014-05-22
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Endothelial cells sense shear stress through rapid changes in membrane physical properties2014

    • Author(s)
      Kimiko Yamamoto and Joji Ando
    • Organizer
      18th International Vascular Biology Meeting (IVBM2014)
    • Place of Presentation
      Miyakomesse, Kyoto
    • Year and Date
      2014-04-17
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Dextran increases differentiation of circulating endothelial progenitor cells2014

    • Author(s)
      Syotaro Obi, Haruchika Masuda, Hiroshi Akimaru, Kimiko Yamamoto, Joji Ando, and Takayuki Asahara
    • Organizer
      18th International Vascular Biology Meeting (IVBM2014)
    • Place of Presentation
      Miyakomesse, Kyoto
    • Year and Date
      2014-04-16
    • Related Report
      2014 Annual Research Report
  • [Presentation] 血流刺激による血管前駆細胞の分化誘導2014

    • Author(s)
      山本希美子、安藤譲二
    • Organizer
      第13回日本再生医療学会総会
    • Place of Presentation
      京都
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] デキストランを用いた血管内皮前駆細胞分化培養法の確立2014

    • Author(s)
      小尾正太郎、増田治史、秋丸裕司、山本希美子、安藤譲二
    • Organizer
      第13回日本再生医療学会総会
    • Place of Presentation
      京都
    • Related Report
      2013 Annual Research Report
  • [Presentation] Dynamic Mechanotransduction in Vascular Cells2013

    • Author(s)
      Kimiko Yamamoto
    • Organizer
      Seminar in the TEMASEK Life Sciences Laboratory, National University Singapore
    • Place of Presentation
      Singapore
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Flow detection and calcium signaling in vascular endothelial cells2013

    • Author(s)
      Kimiko Yamamoto
    • Organizer
      Lecture in the Department of Bioengineering. Imperial College London
    • Place of Presentation
      London
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Vascular endothelial cells respond to shear stress by rapidly decreasing the order of their lipid phases2013

    • Author(s)
      Kimiko Yamamoto and Joji Ando
    • Organizer
      35th Annual International Conference of the IEEE Engineering in Medicine and Biology Society in conjunction with 52nd Annual Conference of Japanese Society for Medical and Biological Engineering
    • Place of Presentation
      Osaka
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Dynamic cellular mechanotransduction and nano-biomechanics2013

    • Author(s)
      Kimiko Yamamoto and Joji Ando
    • Organizer
      8th Aso International Meeting
    • Place of Presentation
      Kumamoto
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 胚性幹細胞のメカノバイオロジー2013

    • Author(s)
      山本希美子、安藤譲二
    • Organizer
      第31回日本ヒト細胞学会学術集会
    • Place of Presentation
      所沢
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] ずり応力が惹起する内皮細胞リン脂質二分子膜の相転移2013

    • Author(s)
      山本希美子
    • Organizer
      第54回Blood Vessel Club
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 血管内皮細胞における血流刺激のメカノセンシング2013

    • Author(s)
      山本希美子、安藤譲二
    • Organizer
      第13回日本NO学会学術集会
    • Place of Presentation
      那覇
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Vascular Mechanobiology: Flow detection and calcium signaling in endothelial cells2013

    • Author(s)
      山本希美子、安藤譲二
    • Organizer
      第36回日本バイオレオロジー学会年会 日韓合同シンポジウム
    • Place of Presentation
      福岡
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Endothelial cells respond to shear stress by decreasing the lipid order of their plasma membranes2013

    • Author(s)
      Kimiko Yamamoto and Joji Ando
    • Organizer
      The 15th International Conference on Biomedical Engineering
    • Place of Presentation
      Singapore
    • Related Report
      2013 Annual Research Report
  • [Presentation] Shear stress rapidly alters the physical properties of vascular endothelial cell membranes by decreasing their lipid order and increasing their fluidity2013

    • Author(s)
      Kimiko Yamamoto, Akira Kamiya, and Joji Ando
    • Organizer
      XIII Mediterranean Conference on Medical and Biological Engineering and Computing
    • Place of Presentation
      Sevilla, Spain
    • Related Report
      2013 Annual Research Report
  • [Presentation] Shear stress increases differentiation of circulating endothelial progenitor cells via the VEGF-R2/PI3K/Akt/mTOR signaling2013

    • Author(s)
      Syotaro Obi, Kimiko Yamamoto, Joji Ando, Haruchika Masuda, and Takayuki Asahara
    • Organizer
      35th Annual International Conference of the IEEE Engineering in Medicine and Biology Society in conjunction with 52nd Annual Conference of Japanese Society for Medical and Biological Engineering
    • Place of Presentation
      Osaka
    • Related Report
      2013 Annual Research Report
  • [Book] メカノバイオロジー:細胞が力を感じ応答する仕組み2015

    • Author(s)
      山本 希美子、安藤 譲二
    • Total Pages
      333
    • Publisher
      化学同人
    • Related Report
      2015 Annual Research Report
  • [Book] 機械工学年鑑2015

    • Author(s)
      山本 希美子
    • Total Pages
      548
    • Publisher
      日本機械学会
    • Related Report
      2015 Annual Research Report
  • [Remarks] 東京大学 大学院医学系研究科 医用生体工学講座 システム生理学

    • URL

      http://square.umin.ac.jp/bme/

    • Related Report
      2014 Annual Research Report
  • [Remarks] 独立行政法人 科学技術振興機構 生命システムの動作原理と基盤技術

    • URL

      http://www.jst.go.jp/kisoken/presto/complete/sysbio/j/sakigake/saki_15.html

    • Related Report
      2014 Annual Research Report
  • [Remarks] 東京大学 大学院医学系研究科 医用生体工学講座 システム生理学

    • URL

      http://square.umin.ac.jp/bme/

    • Related Report
      2013 Annual Research Report
  • [Remarks] 科学技術振興機構 生命システムの動作原理と基盤技術

    • URL

      http://www.jst.go.jp/kisoken/presto/complete/sysbio/j/sakigake/saki_15.html

    • Related Report
      2013 Annual Research Report

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Published: 2013-05-21   Modified: 2019-07-29  

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