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Investigation on the Distribution and Expression of Caveolin-1 in Endothelial Cells under Disturbed Shear Stress by Vertical-Step Flow Chamber

机译:垂直阶梯流室研究剪切应力扰动下内皮细胞中caveolin-1的分布与表达

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Previous researches suggested that caveolae and Caveolin-1 (Cav-1) may regulate the vascular response to lamina shear stress alter. However, atherosclerosis (AS) preferentially affected at the outer edges of vessel bifurcations, where the flow patterns are disturbed. In this study, we fabricated a novel PDMS-based vertical-step flow chamber, which mimics thq disturbed shear flow in AS preferential area of the artery to study the changes of Cav-1 in endothelial cell. Cells were seeded into the flow channel, and then exposed to disturbed shear stress (about 40 dynes/cm2) for 6 hours, 12 hours, 24 hours and 48 hours. It was found that in disturbed flow area, Cav-1 distribution shifted to the membrane from cytoplasm. In early stage of the stimulation, the expression of the Cav-1 decreased both on mRNA and protein level. The expression of Cav-1 in EC showed a significant decrease about 40% after exposure to shear stress for 48 hours. It suggests that disturbed shear stress can affect the distribution and expression of caveolin-1 in endothelial cell, which might play an important role in transducing mechanical stimuli into intracel-lular signals to causes ECs pathological changes and finally it might deduce into atheromatosis process.
机译:先前的研究表明,caveolae和Caveolin-1(Cav-1)可能调节血管对层切应力改变的反应。然而,动脉粥样硬化(AS)在血管分叉的外缘受到优先影响,在该处血管的流动形态受到干扰。在这项研究中,我们制造了一个新颖的基于PDMS的垂直步进流动室,该室模拟动脉AS优先区域中的扰动剪切流,以研究内皮细胞中Cav-1的变化。将细胞接种到流道中,然后暴露于扰动的剪切应力(约40达因/ cm2)中6小时,12小时,24小时和48小时。结果发现,在受干扰的血流区域,Cav-1的分布从细胞质转移到膜上。在刺激的早期,Cav-1的表达在mRNA和蛋白质水平上均下降。暴露于剪切应力48小时后,EC中Cav-1的表达显着降低约40%。提示剪切应力扰动可影响小窝蛋白1在内皮细胞中的分布和表达,这可能在将机械刺激转换为细胞内信号从而引起ECs病理改变中起重要作用,并最终推断出动脉粥样硬化的形成过程。

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