| Project/Area Number |
07408036
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biomedical engineering/Biological material science
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| Research Institution | University of Tokyo |
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Principal Investigator |
KAMIYA Akira University of Tokyo, Institute of Medical Electronics, Faculty of Medicine, Professor, 医学部, 教授 (50014072)
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| Co-Investigator(Kenkyū-buntansha) |
ANDO Joji University of Tokyo, Dept, of Cardiovascular Biomechanics, Faculty of Medicine,, 医学部, 客員助教授 (20159528)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1996: ¥2,800,000 (Direct Cost: ¥2,800,000)
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| Keywords | SHEAR STRESS / ENDOTHELIAL CELL / CALCIUM ION / VCAM-1 / ADHESION MOLECULE / BLOOD FLOW / HEMODYNAMIC FORCE / VCAM-1 / 血管内皮細胞 / 流れずり応力 / 細胞内カルシウム / 血行力学的応力 / 遺伝子 / 細胞内情報伝達系 |
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| Research Abstract |
We applied controlled levels of fluid shear stress to cultured endothelial cells (ECs) in a specially designed flow-loading chamber, and examined the changes in intracellular Ca^<2+> concentrations ([Ca^<2+>]) and adhesion molecule expressions.
When subjected to shear stress in the presence of extracellular ATP,ECs showed the increase in [Ca^<2+>]. Different patterns including peak & plateau, oscillation, and transient were observed in individual cells. The percentage of the pattern was 62%, 32%and6%, respectively. Regardless of the patterns, [Ca^<2+>] increase initiated from specific loci at cell edges, and propagated through the entire cell body as a Ca^<2+> wave. The loci corresponded to the caveolin-rich in ECs, suggesting that the information of shear stress enters via caveolae.
Shear stress inhibited the cell surface expression of vascular adhesion molecule-1 (VCAM-1) in mouse lymphnode venule ECs, and simultaneously decreased the mRNA levels. The decrease in mRNA levels was due to the suppression of VCAM-1 gene transcription, and double AP1 consensus elements in VCAM-1 promoter was essential for the shear-induced suppression of transcriptional activity. This is a negative shear stress responsive element, which was first demonstrated by this study.
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