| Project/Area Number |
09308034
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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 | The University of Tokyo |
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Principal Investigator |
KAMIYA Akira Dept.of Biomedical Engineering, Graduate School of Medicine, The University of Tokyo, Professor, 大学院・医学系研究科, 教授 (50014072)
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| Co-Investigator(Kenkyū-buntansha) |
MASUDA Hirotake Dept.of Pathology, School of Medicine, Akita Univ., Professor, 医学部, 教授 (60103462)
ANDO Joji Dept.of Biomedical Engineering, Graduate School of Medicine, The University of T, 大学院・医学系研究科, 助教授 (20159528)
SHIBATA Masahiro Dept.of Biomedical Engineering, Graduate School of Medicine, The University of T, 大学院・医学系研究科, 講師 (60158954)
是永 理佐 東京大学, 大学院・医学系研究科, 寄付講座教員 (20260482)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥27,100,000 (Direct Cost: ¥27,100,000)
Fiscal Year 1998: ¥5,300,000 (Direct Cost: ¥5,300,000)
Fiscal Year 1997: ¥21,800,000 (Direct Cost: ¥21,800,000)
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| Keywords | shear stress / endothelial cell / angiogenesis / hemodynamics force / intravital microscope / vasodilator / 微小循環 / 血管リモデリング / GM-CSF / 遺伝子発現 / 毛細血管新生 / 血管拡張剤 / 生体蛍光顕微鏡 / 血流速度 / 微小血管内径 / ラビットイヤーチャンバー / 創傷治癒 |
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| Research Abstract |
The aim of the present study was to analyze the mechanisms for physiological angiogenesis or pathological intimal thickening from a view point of vascular responses to shear stress produced by flowing blood. The effect of an increase in blood flow on new microvascular formation was studied in vivo. Using an intravital microscopic technique, we observed die process of new microvascular formation in the ear chamber of rabbits treated with alpha 1 blocker (prazosin) for 7-23 days. The prazosin-treated (blood flow-loaded) rabbits showed a marked increase in microvascular formation. The ultimate vascular density in the prazosin-treated rabbit was almost 21% higher than that in the control rabbit Various growth factors and cytokines which are secreted from endothelial cells are involved in vascular intimal thickening. The effect of shear stress on the production of cylokines by endothelial cells was investigated in vitro. Cultured human umbilical vein endothelial cells were subjected to a shear stress of 15 dynes/cm^2 for 24 h in a parallel plate type of flow-loading device and the changes in the concentration of granulocyte/macrophage-colony stimulating factor (GM-CSF) were determined by ELISA.Shear stress increased the production of GM-CSF 6-times the control level, while it had no effect on the production of other CSFs such as granulocyte-CSF and macrophage-CSF.Both run-on assay and luciferase assay demonstrated that shear stress did not affect transcription of GM-CSF gene, but actinomycin-D chase experiments revealed that the half-life of GM-CSF mRNA was significantly longer in shear-stressed cells than that in control cells. This indicates that shear stress augments GM-CSF production in endothelial cells via mRNA stabilization.
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