Visualization and analyses of endothelial response to flow during vascular formation and remodeling
| Project/Area Number |
17K08560
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
General physiology
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| Research Institution | National Cardiovascular Center Research Institute |
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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)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| 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)
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| 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 |
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| 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.
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| 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。
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Report
(4 results)
Research Products
(31 results)
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[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.
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Journal Title
Circ. Res.
Volume: 120
Issue: 8
Pages: 1276-1288
DOI
Related Report
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
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