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

包埋在动脉介质中的血管平滑肌细胞（VSMC）通常被屏蔽以免受流动血液的直接剪切应力，并且在血管损伤后暴露于直接血流。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，我们采用一种新发展的单光子计数技术研究了流体流切应力对人主动脉平滑肌细胞（HASMCs）[Ca^2+]i的影响。在细胞外Ca^2+浓度为2.0mM的情况下，对HASMC单层顶面施加16达因/cm ^2的剪切应力60 s，可引起细胞内[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响应流体流切应力而增加胞浆Ca^<2+>浓度，另一方面，我们建立了一个二维数值模拟模型，以解决IEL对介质中大分子对流扩散运输的影响。该模型考虑了中间层的间隙流，由于IEL中存在泄漏的开窗孔，因此中间层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，确定在介质中的分子运输和摄取的一系列有趣的功能。此外，我们观察到，运输的LDL到SMC表面可能是有限的流体相（表面浓度小于散装浓度），而ATP的运输是有限的SMC表面上的反应（表面浓度等于散装浓度）。

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).