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Physiological functions of the human arterial smooth muscle cell response to the fluid mechanical force

人动脉平滑肌细胞对流体机械力反应的生理功能

基本信息

批准号：
14550142
负责人：
TADA Shigeru
金额：
$ 2.05万
依托单位：
Tokyo Institute of Technology
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-14550142/
关键词：
Smooth muscle cells Wall shear stress Calcium signal transduction mass transport Low density lipo protein ATP フォトンカウンティング法

项目摘要

Vascular smooth muscle cells (VSMCs) embedded in an arterial medium are normally shielded from the direct shear stress of flowing blood and are exposed to direct blood flow after vascular injury. Because of the importance of intracellular Ca^<2+> concentration ([Ca^<2+>]i) in regulating vascular tone and functions, we investigated the effect of fluid flow shear stress on [Ca^<2+>]i in human aortic smooth muscle cells (HASMCs) in terms of a newly developed single-photon counting technique. In the presence of 2.0mM extracellular Ca^<2+>, a shear stress of [16 dynes/cm^2] applied for 60 s to the top surface of the HASMC monolayer elicited a sharp increase in [Ca^<2+>]i followed by multiple elevation of lesser magnitude. Results suggest that the influx of extracellular Ca^<2+> contributes to the increase in the cytosolic Ca^<2+> concentration of VSMCs in response to fluid flow shear stress.On the other hand, we have developed a two-dimensional numerical simulation model to resolve the influence of the IEL on convective-diffusive transport of macromolecules in the media. The model considers interstitial flow in the medial layer that has a complex entrance condition due to the presence of leaky fenestral pores in the IEL. Results for ATP and LDL demonstrate a range of interesting features of molecular transport and uptake in the media that are determined by considering the balance among convection, diffusion and SMC surface reaction. In addition we observe that transport of LDL to SMC surfaces is likely to be limited by the fluid phase (surface concentration less than bulk concentration), whereas ATP transport is limited by reaction on the SMC surface (surface concentration equals bulk concentration).

血管平滑肌细胞（VSMCs）包埋在动脉介质中，通常不受流动血液的直接剪切应力的影响，并且在血管损伤后暴露于直接的血流中。由于细胞内Ca^<2+>浓度（[Ca^<2+>]i）在调节血管张力和功能中的重要性，我们利用新开发的单光子计数技术研究了流体剪切应力对人主动脉平滑肌细胞（HASMCs） [Ca^<2+>]i的影响。在2.0mM细胞外Ca^<2+>存在的情况下，在HASMC单层的上表面施加[16达因/cm^2] 60 s的剪切应力，引起[Ca^<2+>]i的急剧增加，随后出现多次较小幅度的升高。结果表明，细胞外Ca^<2+>的内流有助于VSMCs响应流体剪切应力时胞内Ca^<2+>浓度的增加。另一方面，我们建立了一个二维数值模拟模型来解决IEL对介质中大分子对流扩散输运的影响。该模型考虑了内层的间隙流动，由于IEL中存在渗漏的门框孔，该内层的间隙流动具有复杂的入口条件。ATP和LDL的结果表明，通过考虑对流、扩散和SMC表面反应之间的平衡，分子在介质中的运输和摄取具有一系列有趣的特征。此外，我们观察到LDL到SMC表面的运输可能受到流体相的限制（表面浓度小于体积浓度），而ATP的运输则受到SMC表面反应的限制（表面浓度等于体积浓度）。