1994 Fiscal Year Final Research Report Summary
Bio-engineering study on the mechanism of endothelial cell responses to blood flow
| Project/Area Number |
03404062
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| Research Category |
Grant-in-Aid for General Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
医学一般
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| Research Institution | Institute of Medical Electronics, Faculty of Medicine, Univ.of Tokyo |
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Principal Investigator |
KAMIYA Akira Faculty-of Medicine, Univ.Tokyo, Professor, 医学部(医), 教授 (50014072)
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| Co-Investigator(Kenkyū-buntansha) |
SHIBATA Masahiro Faculty of Medicine, Univ.Tokyo, Lecturer, 医学部(医), 講師 (60158954)
ANDO Joji Faculty of Medicine, Univ.Tokyo, Guest Associate Professor, 医学部(医), 客員助教授 (20159528)
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| Project Period (FY) |
1991 – 1994
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| Keywords | Endothelila cells / Calcium ion / Nitric oxide / Shear stress / Adhesion molecule / VCAM-1 |
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| Research Abstract |
To elucidate the mechanism of vascular endothelial cell (EC) responses to blood flow, cultured ECs were exposed to controlled levels of shear stress in a flow-loading device and their responses were examined in vitro. Concretely, three different experiments were performed in this project ; 1) as regards the signal transduction of shear stress, changes in intracellular Ca^<++> concentration ([Ca^<++>]) were monitored by a calcium indicator, Fura-2, and fluorescence photomicroscopy when ECs were subjected to shear stress. 2) as to cell responses to shear stress, the production of nitric oxide, a potent vasodilator, by ECs was measured. 3) as to shear stress effect on gene expression, changes in the mRNA levels of adhesion molecules were analyzed with reverse transcriptase/polymerase chain reaction method. The results obtained are as follows.
1) Application of medium flow increased [Ca^<++>] in ECs. The response needs the presence of extracellular ATP,and at 500 nM ATP,[Ca^<++>] increased in proportion to flow rate. Flow-loading experiments using two perfusates with different viscosities revealed that flow-induced [Ca^<++>] increase in shear stress-rather that shear rate-dependent.
2) Shear stress stimulated nitric oxiide production by ECs.
3) Shear stress decreased the mRNA level of vascular adhesion molecule-1 in mouse venule ECs, and at the same time down regulated the cell surface expression.
These data suggest that vascular ECs can perceive shear stress generated by blood flow and alter their functions in both protein and gene levels, which is probably involved in flow-dependent vascular structuring and atherogenesis.
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