Interaction between the Stress Phase Angle (SPA) and the Oscillatory Shear Index (OSI) Affects Endothelial Cell Gene Expression.
Interaction between the Stress Phase Angle (SPA) and the Oscillatory Shear Index (OSI) Affects Endothelial Cell Gene Expression.
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DOI：
10.1371/journal.pone.0166569
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Tarbell JM
中科院分区：
文献类型：
--
作者：
Amaya R;Cancel LM;Tarbell JM
血流动力学在动脉粥样硬化病变的不均匀分布中起重要作用。内皮细胞同时暴露于流体壁剪切应力（WSS）和固体周向应力（CS）。由于动脉循环中阻抗（全局因素）和几何复杂性（局部因素）的变化，这两种力之间存在时间滞后，可以通过CS和WSS（应力相位角- spa）之间的时间相位角来表征。在冠状动脉中最突出的非同步血流（SPA接近-180°）与动脉粥样硬化的局限性有关。以振荡剪切指数（OSI）大于零为特征的反向振荡流动也与动脉粥样硬化定位有关。在这项研究中，我们研究了异步流动和反向流动在改变37个与动脉粥样硬化发展相关的基因表达方面的关系。在逆转振荡血流的情况下，我们观察到与同步血流动力学相比，异步条件上调了8个基因，其中大多数是促动脉粥样硬化。western blot证实促炎转录因子NFκB p65上调，免疫荧光染色证实NFκB p65核易位。非反转流动与反转流动的对比研究发现，在同步血流动力学情况下，反转流动改变了11个基因的表达，而在非同步血流动力学情况下，反转流动改变了17个基因的表达。在同步和异步条件下，逆转血流均显著上调NFκB p65的蛋白表达。在血流逆转的情况下，NFκB p65的核易位在同步和异步条件下被证实。这些数据表明，与无剪切应力逆转的同步血流动力学相比，非同步血流动力学和逆转血流可引起内皮细胞的促动脉粥样硬化反应，表明SPA和逆转血流（OSI）是表征动脉易感性的重要参数。
Hemodynamic forces play an important role in the non-uniform distribution of atherosclerotic lesions. Endothelial cells are exposed simultaneously to fluid wall shear stress (WSS) and solid circumferential stress (CS). Due to variations in impedance (global factors) and geometric complexities (local factors) in the arterial circulation a time lag arises between these two forces that can be characterized by the temporal phase angle between CS and WSS (stress phase angle–SPA). Asynchronous flows (SPA close to -180°) that are most prominent in coronary arteries have been associated with localization of atherosclerosis. Reversing oscillatory flows characterized by an oscillatory shear index (OSI) that is great than zero are also associated with atherosclerosis localization. In this study we examined the relationship between asynchronous flows and reversing flows in altering the expression of 37 genes relevant to atherosclerosis development. In the case of reversing oscillatory flow, we observed that the asynchronous condition upregulated 8 genes compared to synchronous hemodynamics, most of them proatherogenic. Upregulation of the pro-inflammatory transcription factor NFκB p65 was confirmed by western blot, and nuclear translocation of NFκB p65 was confirmed by immunofluorescence staining. A comparative study between non-reversing flow and reversing flow found that in the case of synchronous hemodynamics, reversing flow altered the expression of 11 genes, while in the case of asynchronous hemodynamics, reversing flow altered the expression of 17 genes. Reversing flow significantly upregulated protein expression of NFκB p65 for both synchronous and asynchronous conditions. Nuclear translocation of NFκB p65 was confirmed for synchronous and asynchronous conditions in the presence of flow reversal. These data suggest that asynchronous hemodynamics and reversing flow can elicit proatherogenic responses in endothelial cells compared to synchronous hemodynamics without shear stress reversal, indicating that SPA as well as reversal flow (OSI) are important parameters characterizing arterial susceptibility to disease.
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DOI：
10.1115/1.429629
发表时间：
2000-02-01
影响因子：
1.7
作者：
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通讯作者：
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DOI：
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作者：
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DOI：
10.1161/01.atv.0000147118.97474.4b
发表时间：
2004-12-01
影响因子：
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作者：
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