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Disturbed flow mediated modulation of shear forces on endothelial plane: A proposed model for studying endothelium around atherosclerotic plaques

机译:扰动介导的血管内皮细胞剪切力调节:研究动脉粥样硬化斑块周围内皮的模型

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摘要

Disturbed fluid flow or modulated shear stress is associated with vascular conditions such as atherosclerosis, thrombosis, and aneurysm. In vitro simulation of the fluid flow around the plaque micro-environment remains a challenging approach. Currently available models have limitations such as complications in protocols, high cost, incompetence of co-culture and not being suitable for massive expression studies. Hence, the present study aimed to develop a simple, versatile model based on Computational Fluid Dynamics (CFD) simulation. Current observations of CFD have shown the regions of modulated shear stress by the disturbed fluid flow. To execute and validate the model in real sense, cell morphology, cytoskeletal arrangement, cell death, reactive oxygen species (ROS) profile, nitric oxide production and disturbed flow markers under the above condition were assessed. Endothelium at disturbed flow region which had been exposed to low shear stress and swirling flow pattern showed morphological and expression similarities with the pathological disturbed flow environment reported previously. Altogether, the proposed model can serve as a platform to simulate the real time micro-environment of disturbed flow associated with eccentric plaque shapes and the possibilities of studying its downstream events.
机译:流体流动紊乱或剪切应力调节与诸如动脉粥样硬化,血栓形成和动脉瘤的血管状况有关。斑块微环境周围流体流动的体外模拟仍然是一个具有挑战性的方法。当前可用的模型具有局限性,例如方案复杂,成本高,共培养能力差并且不适用于大规模表达研究。因此,本研究旨在开发基于计算流体动力学(CFD)模拟的简单,通用模型。 CFD的当前观察结果表明,受扰动的流体流动会调制剪切应力区域。为了真实地执行和验证该模型,评估了在上述条件下的细胞形态,细胞骨架排列,细胞死亡,活性氧(ROS)分布,一氧化氮生成和流动标记紊乱。在扰动流动区的内皮受到了低剪切应力和涡流模式的影响,其形态和表达与先前报道的病理性扰动流动环境相似。总之,所提出的模型可以作为模拟与偏心斑块形状相关的扰动流动的实时微环境和研究其下游事件的可能性的平台。

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