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Molecular Biological and Bio-Engineering Study of Blood Flow-Sensing and Responding Mechanism of Vascular Endothelial Cells.

血管内皮细胞血流感知与响应机制的分子生物学和生物工程研究。

基本信息

批准号：
01440085
负责人：
KAMIYA Akira
金额：
$ 6.66万
依托单位：
Institute of Medical Electronics, Faculty of Medicine, University of Tokyo (1990)Hokkaido University (1989)
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (A)
财政年份：
1989
资助国家：
日本
起止时间：
1989 至 1990
项目状态：
已结题

项目摘要

The hemodynamic force of blood flow is speculated to modulate endothelial cell functions and play an important role in the regulation of the structure of the vessel and in the initiation of early lesions of atherosclerosis. To prove this hypothesis, we studied how vascular endothelial cells recognize the hemodynamic changes in blood flow and modulate their functions. By using a flow-loading apparatus hydrodynamically designed in our laboratory, we applied fluid flow to cultured vascular endothelial cells, and studied the changes in cytoplasmic free calcium ion concentrations, ability of endothelial regeneration, DNA synthesis, production and secretion of collagen, and release of endothelium-derived relaxing factor (EDRF). The results obtained were as follows : 1) Application of medium flow to endothelial cells induced a transient rise in cytoplasmic calcium concentrations. The flow-inducedcalcium response needed the presence of ATP in perfusion fluids and, especially at 500 nM ATP, end … More othelial cells showed the gradual increase in calcium concentrations in response to the gradual increase in flow (shear stress ranging from 0 to 42 dyn/cm^2), indicating that endothelial cells perceive flow (shear stress) as a stimulus via a second messenger, calcium ion. 2) Application of flow yielding shear stress of 1-3 dyn/cm^2 for 24-48 hours stimulated endothelial cell migration and proliferation during regeneration after mechanical denudation. Cell migration occurred downstream prominently. Flow application also enhanced DNA synthesis by endothelial cells during regeneration and increased the percentage of the cells locating in the mitotic phase of the cell cycle. Furthermore, endothelial cells reacted to flow to produce stimulators of smooth muscle cell migration. Endotial cells produce collagen, an extracellular matrix, and EDRF which relaxes smooth muscle cells and inhibits platelets aggregation, and these functions were stimulated by flow application. It was also observed that the flow-induced release of EDRF by endothelial cells relate to the flow-induced calcium transients. Less

推测血流的血流动力学力可以调节内皮细胞的功能，并在血管结构的调节和动脉粥样硬化早期病变的发生中发挥重要作用。为了证明这一假设，我们研究了血管内皮细胞如何识别血流动力学变化并调节其功能。利用本实验室自行设计的流体动力学加载装置，对体外培养的血管内皮细胞进行流体加载，研究其胞质游离钙离子浓度、内皮细胞再生能力、DNA合成、胶原蛋白的产生和分泌以及内皮源性松弛因子（EDRF）释放的变化。结果表明：1)对内皮细胞施加介质流可引起细胞质钙浓度的短暂升高。血流诱导的钙反应需要灌注液中ATP的存在，特别是在500 nM ATP时，更多的内皮细胞显示出钙浓度随着血流的逐渐增加而逐渐增加（剪切应力范围从0到42 dyn/cm^2），这表明内皮细胞通过第二信使钙离子将血流（剪切应力）视为刺激。2)施加1-3 dyn/cm^2的流变屈服剪切应力24-48小时，刺激内皮细胞在机械剥蚀后再生过程中的迁移和增殖。细胞迁移主要发生在下游。流动应用也增强了再生过程中内皮细胞的DNA合成，并增加了处于细胞周期有丝分裂期的细胞的百分比。此外，内皮细胞对血流产生反应，产生平滑肌细胞迁移的刺激物。内质细胞产生胶原蛋白，一种细胞外基质和EDRF， EDRF可以放松平滑肌细胞并抑制血小板聚集，这些功能被血流应用刺激。我们还观察到内皮细胞血流诱导的EDRF释放与血流诱导的钙瞬态有关。少