PDF(Pubmed)
Abstract：
Disturbed flow is one of the pathological initiators of endothelial dysfunction in intimal hyperplasia (IH) which is commonly seen in vascular bypass grafts, and arteriovenous fistulas. Various in vitro disease models have been designed to simulate the hemodynamic conditions found in the vasculature. Nonetheless, prior investigations have encountered challenges in establishing a robust disturbed flow model, primarily attributed to the complex bifurcated geometries and distinctive flow dynamics. In the present study, we aim to address this gap by introducing an in vitro bypass flow model capable of inducing disturbed flow and other hemodynamics patterns through a pulsatile flow in the same model. To assess the model\'s validity, we employed computational fluid dynamics (CFD) to simulate hemodynamics and compared the morphology and functions of human umbilical venous endothelial cells (HUVECs) under disturbed flow conditions to those in physiological flow or stagnant conditions. CFD analysis revealed the generation of disturbed flow within the model, pinpointing the specific location in the channel where the effects of disturbed flow were observed. High-content screening, a single-cell morphological profile assessment, demonstrated that HUVECs in the disturbed flow area exhibited random orientation, and morphological features were significantly distinct compared to cells in the physiological flow or stagnant condition after a two days of flow exposure. Furthermore, HUVECs exposed to disturbed flow underwent extensive remodeling of the adherens junctions and expressed higher levels of endothelial cell activation markers compared to other hemodynamic conditions. In conclusion, our in vitro bypass flow model provides a robust platform for investigating the associations between disturbed flow pattern and vascular diseases.
摘要：
血流紊乱是血管旁路移植术中常见的内膜增生（IH）内皮功能障碍的病理引发者之一。和动静脉瘘.已经设计了各种体外疾病模型来模拟在脉管系统中发现的血液动力学条件。尽管如此，先前的研究在建立鲁棒的扰动流模型方面遇到了挑战，主要归因于复杂的分叉几何形状和独特的流动动力学。在本研究中,我们的目标是通过引入体外旁路流模型来解决这一差距，该模型能够通过相同模型中的脉动流诱导干扰流和其他血液动力学模式。为了评估模型的有效性，我们采用计算流体动力学(CFD)模拟血液动力学,并比较了受干扰流动条件下与生理流动或停滞条件下的人脐静脉内皮细胞(HUVEC)的形态和功能.CFD分析揭示了模型内扰动流的产生，精确定位通道中观察到扰动流影响的具体位置。高内容筛选,单细胞形态轮廓评估，证明了受干扰流动区域的HUVEC表现出随机取向，与处于生理流动或停滞状态的细胞相比，两天的流动暴露后，形态特征显着不同。此外，与其他血液动力学条件相比，暴露于受干扰的HUVEC经历了粘附连接的广泛重塑，并表达了更高水平的内皮细胞活化标志物。总之,我们的体外旁路血流模型为研究血流模式紊乱与血管疾病之间的关联提供了一个强大的平台.
