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

埋藏在动脉介质中的血管平滑肌细胞(VSMCs)通常不受流动血液的直接剪应力的影响，在血管损伤后暴露于直接血流中。鉴于细胞内钙离子浓度([Ca^&lt；2+&gt；]i)在调节血管张力和功能中的重要作用，我们利用一种新的单光子计数技术，研究了流体切应力对人主动脉平滑肌细胞(HASMCs)[Ca^&lt；2+&gt；]i的影响。当细胞外钙浓度为2.0 mM时，60 S作用于血管内皮细胞单层顶面的剪应力为[16dynes/cm~2]，引起细胞内[Ca~(2+)]i急剧升高，并出现较小幅度的倍增。结果表明，细胞外Ca~(2+)~(2+)的内流导致VSMC胞内Ca~(2+)浓度随流体剪切力的增加而增加。另一方面，我们发展了一个二维数值模拟模型来研究IEL对介质中大分子对流扩散传输的影响。该模型考虑了内侧层中的间质流动，由于IEL中存在泄漏的窗孔，因此具有复杂的进入条件。ATP和低密度脂蛋白的结果显示了一系列有趣的分子在介质中传输和吸收的特征，这些特征是通过考虑对流、扩散和SMC表面反应之间的平衡来确定的。此外，我们还观察到，低密度脂蛋白向SMC表面的转运可能受到液体相(表面浓度小于本体浓度)的限制，而ATP的转运则受到SMC表面反应(表面浓度等于本体浓度)的限制。

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).