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Visualization and analyses of endothelial response to flow during vascular formation and remodeling

Research Project

Project/Area Number 17K08560
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General physiology
Research InstitutionNational Cardiovascular Center Research Institute

Principal Investigator

Nakajima Hiroyuki  国立研究開発法人国立循環器病研究センター, 研究所, 室長 (10467657)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords血管形成 / メカニカルストレス / 血流 / 血管リモデリング / 血管新生 / シアストレス / 流れ刺激
Outline of Final Research Achievements

We examined where and how blood flow controls vascular formation and found that blood flow regulates angiogenesis and vascular remodeling especially in the head region of zebrafish. We found that intracellular Ca2+ oscillations occur in endothelial cells in response to flow. These Ca2+ responses are also regulated by VEGFA/VEGFR2 signaling. Our time-lapse Ca2+ imaging in high spatial and time resolution has succeeded in visualizing endothelial responses to blood flow thereby revealed the mode of angiogenesis regulated by blood flow. In addition, we have visualized the involvement of chemokine signaling and macrophages in vascular development in the brain central arteries. Thus, our results will lead to understanding the mechanisms how blood flow regulates vascular formation in vivo.

Academic Significance and Societal Importance of the Research Achievements

血流による機械的刺激が生体の血管形成をどのように制御しているのかについては未解明な部分が多い。本研究では血流に対する応答を生きたまま観察することに成功しており、血流依存的な血管新生および血管リモデリングに際して、内皮細胞がいつ、どこで、血流に応答しているのかを明らかにした点で、高い学術的意義を有する。また、血流によるメカニカルファクターは、動脈硬化をはじめとする成人病の種々の病態とも深く関わることから、様々なパターンの血流に対する血管内皮細胞の応答を理解することは、血管を主因とする様々な疾患機序の解明や治療に繋がる社会的意義のある研究と言える。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (31 results)

All 2019 2018 2017 Other

All Int'l Joint Research (4 results) Journal Article (9 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 8 results,  Open Access: 5 results,  Acknowledgement Compliant: 1 results) Presentation (16 results) (of which Int'l Joint Research: 4 results,  Invited: 4 results) Book (2 results)

  • [Int'l Joint Research] The University of Queensland(オーストラリア)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] Max Planck Institute/Potsdam University(ドイツ)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] The University of Queensland/Victor Chang Cardiac Research Institute(オーストラリア)

    • Related Report
      2018 Research-status Report
  • [Int'l Joint Research] Max Planck Institute(ドイツ)

    • Related Report
      2018 Research-status Report
  • [Journal Article] Biomechanical signaling within the developing zebrafish heart attunes endocardial growth to myocardial chamber dimensions2019

    • Author(s)
      Bornhorst Dorothee、Xia Peng、Nakajima Hiroyuki、Dingare Chaitanya、Herzog Wiebke、Lecaudey Virginie、Mochizuki Naoki、Heisenberg Carl-Philipp、Yelon Deborah、Abdelilah-Seyfried Salim
    • Journal Title

      Nature Communications

      Volume: 10 Issue: 1 Pages: 1-10

    • DOI

      10.1038/s41467-019-12068-x

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Yap1 promotes sprouting and proliferation of lymphatic progenitors downstream of Vegfc in the zebrafish trunk.2019

    • Author(s)
      Grimm L, Nakajima H, Chaudhury S, Bower NI, Okuda KS, Cox AG, Harvey NL, Koltowska K, Mochizuki N, Hogan BM.
    • Journal Title

      Elife

      Volume: 8

    • DOI

      10.7554/elife.42881

    • Related Report
      2019 Annual Research Report 2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] ゼブラフィッシュを用いた血管研究2019

    • Author(s)
      中嶋洋行
    • Journal Title

      医学のあゆみ

      Volume: 270 Pages: 63-69

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ゼブラフィッシュを用いた血管研究について2019

    • Author(s)
      中嶋洋行
    • Journal Title

      医学のあゆみ

      Volume: 印刷中

    • Related Report
      2018 Research-status Report
  • [Journal Article] Hippo signaling determines the number of venous pole cells that originate from the anterior lateral plate mesoderm in zebrafish.2018

    • Author(s)
      Fukui H, Miyazaki T, Chow RW, Ishikawa H, Nakajima H, Vermot J, Mochizuki N.
    • Journal Title

      Elife

      Volume: 7 Pages: 1-24

    • DOI

      10.7554/elife.29106

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Blood Flow-mediated YAP Regulation and Its Role in Vessel Maintenance2018

    • Author(s)
      中嶋洋行
    • Journal Title

      Seibutsu Butsuri

      Volume: 58 Issue: 3 Pages: 155-158

    • DOI

      10.2142/biophys.58.155

    • NAID

      130007378615

    • ISSN
      0582-4052, 1347-4219
    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Vascular Endothelial Growth Factor-Dependent Sprouting Angiogenesis Assay Based on an In Vitro Human Blood Vessel Model for the Study of Anti-Angiogenic Drugs2018

    • Author(s)
      Pauty Joris、Usuba Ryo、Cheng Irene Gayi、Hespel Louise、Takahashi Haruko、Kato Keisuke、Kobayashi Masayoshi、Nakajima Hiroyuki、Lee Eujin、Yger Florian、Soncin Fabrice、Matsunaga Yukiko T.
    • Journal Title

      EBioMedicine

      Volume: 27 Pages: 225-236

    • DOI

      10.1016/j.ebiom.2017.12.014

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Flow pattern-dependent endothelial cell responses through transcriptional regulation.2017

    • Author(s)
      Nakajima H, Mochizuki N.
    • Journal Title

      Cell Cycle

      Volume: 16 Issue: 20 Pages: 1893-1893

    • DOI

      10.1080/15384101.2017.1364324

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Polydom is an extracellular matrix protein involved in lymphatic vessel remodeling.2017

    • Author(s)
      Morooka, N., Futaki, S., Sato-Nishiuchi, R., Nishino, M., Totani, Y., Shimono, C., Nakano, I., Nakajima, H., Mochizuki, N., and Sekiguchi, K.
    • Journal Title

      Circ. Res.

      Volume: 120 Issue: 8 Pages: 1276-1288

    • DOI

      10.1161/circresaha.116.308825

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] 体節形成期に尾側の血管内皮細胞を供給する新たな起源細胞の同定2019

    • Author(s)
      中嶋 洋行、石川 博之、望月 直樹
    • Organizer
      第26回日本血管生物医学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ゼブラフィッシュ血管新生におけるVEGFA/VEGFR2シグナルのイメージング解析/Imaging-based analyses of VEGFA/VEGFR2 signaling during angiogenesis in zebrafish2019

    • Author(s)
      中嶋洋行、福本萌、望月直樹
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Analyses of flow-dependent angiogenesis in zebrafish2019

    • Author(s)
      Hiroyuki Nakajima, Naoki Mochizuki
    • Organizer
      Inaugural Joint Scientific Meeting of AVBS | ANZMS | AAVBM
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ゼブラフィッシュを用いた血管形成の生体イメージング解析2019

    • Author(s)
      中嶋洋行
    • Organizer
      第12回若手研究フォーラム
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] ゼブラフィッシュ初期胚における血管内皮細胞の新たな起源細胞の同定2019

    • Author(s)
      中嶋洋行
    • Organizer
      第5回血管生物若手研究会
    • Related Report
      2018 Research-status Report
  • [Presentation] A novel type of flow-dependent angiogenesis in zebrafish2018

    • Author(s)
      Hiroyuki Nakajima, Naoki Mochizuki
    • Organizer
      Weinstein2018
    • Related Report
      2018 Research-status Report 2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] A novel type of flow-dependent angiogenesis in zebrafish2018

    • Author(s)
      Hiroyuki Nakajima, Naoki Mochizuki
    • Organizer
      IVBM2018
    • Related Report
      2018 Research-status Report 2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Imaging-based analyses of vascular development using zebrafish2018

    • Author(s)
      Hiroyuki Nakajima
    • Organizer
      iCeMS Seminar
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] Analysis of novel flow-dependent angiogenesis in zebrfish2018

    • Author(s)
      Hiroyuki Nakajima, Naoki Mochizuki
    • Organizer
      11th Kloster Seeon Meeting "Angiogenes"
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Imaging-based analyses of vascular development mediated by angiogenic and2018

    • Author(s)
      Hiroyuki Nakajima
    • Organizer
      Max Planck Institute for Molecular Biomedicine Seminar
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] Imaging-based Analyses of Vascular Development Mediated by Angiogenic and Mechanical Cues2018

    • Author(s)
      Hiroyuki Nakajima
    • Organizer
      University Basel BIOZENTRUM Seminar
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 血流によるメカニカルストレスに依存した新規血管新生機構の解析2018

    • Author(s)
      中嶋洋行、 望月直樹
    • Organizer
      第26回日本血管生物医学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] 血管内皮細胞のYAPは流れによる機械的刺激に応答してゼブラフィッシュの血管安定化に寄与する/Endothelial YAP responds to flow-mediated mechanical stimuli and contributes to vessel stabilization in zebrafish2017

    • Author(s)
      中嶋洋行、望月直樹
    • Organizer
      2017年度生命科学系学会合同年次大会(ConBio2017)
    • Related Report
      2017 Research-status Report
  • [Presentation] ゼブラフィッシュ血管形成過程における内皮細胞応答のライブイメージング解析2017

    • Author(s)
      中嶋洋行
    • Organizer
      国立循環器病研究センター・産業技術総合研究所バイオメディカル研究部門若手会合同セミナー2017
    • Related Report
      2017 Research-status Report
  • [Presentation] 血流による機械的刺激に対する新たな内皮細胞応答機構の解明2017

    • Author(s)
      中嶋洋行、福原茂朋、望月直樹
    • Organizer
      Molecular Cardiovascular Metabolic Conference
    • Related Report
      2017 Research-status Report
  • [Presentation] YAPは流れ刺激に応答してゼブラフィッシュの血管安定化に寄与する/Endothelial YAP is regulated by flow-mediated mechanical stimuli and contributes to vessel stabilization in zebrafish2017

    • Author(s)
      中嶋洋行、望月直樹
    • Organizer
      第69回日本細胞生物学会
    • Related Report
      2017 Research-status Report
  • [Book] 生物物理(6月掲載予定)2018

    • Author(s)
      中嶋洋行
    • Total Pages
      3
    • Publisher
      日本生物物理学会
    • Related Report
      2017 Research-status Report
  • [Book] 循環器病研究の進歩2017

    • Author(s)
      福井一、千葉綾乃、宮崎敬大、石川博之、島本恵子、中嶋洋行、望月直樹
    • Total Pages
      9
    • Publisher
      協和企画
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2022-12-28  

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