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首页> 美国卫生研究院文献>other >The Interaction between Fluid Wall Shear Stress and Solid Circumferential Strain Affects Endothelial Gene Expression
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The Interaction between Fluid Wall Shear Stress and Solid Circumferential Strain Affects Endothelial Gene Expression

机译：流体壁剪切应力与固体圆周应变之间的相互作用影响内皮基因表达。

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Endothelial cells lining the walls of blood vessels are exposed simultaneously to wall shear stress (WSS) and circumferential stress (CS) that can be characterized by the temporal phase angle between WSS and CS (stress phase angle – SPA). Regions of the circulation with highly asynchronous hemodynamics (SPA close to -180°) such as coronary arteries are associated with the development of pathological conditions such as atherosclerosis and intimal hyperplasia whereas more synchronous regions (SPA closer to 0°) are spared of disease. The present study evaluates endothelial cell gene expression of 42 atherosclerosis-related genes under asynchronous hemodynamics (SPA=-180 °) and synchronous hemodynamics (SPA=0 °). This study used a novel bioreactor to investigate the cellular response of bovine aortic endothelial cells (BAECS) exposed to a combination of pulsatile WSS and CS at SPA=0 or SPA=-180. Using a PCR array of 42 genes, we determined that BAECS exposed to non-reversing sinusoidal WSS (10±10 dyne/cm2) and CS (4 ± 4 %) over a 7 hour testing period displayed 17 genes that were up regulated by SPA = -180 °, most of them pro-atherogenic, including NFκB and other NFκB target genes. The up regulation of NFκB p50/p105 and p65 by SPA =-180° was confirmed by Western blots and immunofluorescence staining demonstrating the nuclear translocation of NFκB p50/p105 and p65. These data suggest that asynchronous hemodynamics (SPA=-180 °) can elicit proatherogenic responses in endothelial cells compared to synchronous hemodynamics without shear stress reversal, indicating that SPA may be an important parameter characterizing arterial susceptibility to disease.
机译：衬在血管壁上的内皮细胞同时暴露于壁切应力（WSS）和周向应力（CS），其特征在于WSS和CS之间的时间相角（应力相角– SPA）。血液动力学高度不同步（SPA接近-180°）的循环区域（如冠状动脉）与诸如动脉粥样硬化和内膜增生等病理状况的发展有关，而更同步的区域（SPA接近0°）则免于疾病的困扰。本研究评估了异步血液动力学（SPA = -180°）和同步血液动力学（SPA = 0°）下42个动脉粥样硬化相关基因的内皮细胞基因表达。这项研究使用一种新型的生物反应器来研究暴露于SPA = 0或SPA = -180的脉动WSS和CS组合的牛主动脉内皮细胞（BAECS）的细胞反应。使用42个基因的PCR阵列，我们确定在7个小时的测试期间内，BAECS暴露于不可逆的正弦WSS（10±10达因/ cm 2 ）和CS（4±4％）由SPA = -180°上调的17个基因，其中大多数是促动脉粥样硬化的，包括NFκB和其他NFκB靶基因。通过蛋白质印迹和免疫荧光染色证实了SPA = -180°对NFκBp50 / p105和p65的上调，证明了NFκBp50 / p105和p65的核易位。这些数据表明，与没有剪切应力逆转的同步血液动力学相比，异步血液动力学（SPA = -180°）可以在内皮细胞中引发前动脉粥样硬化反应，这表明SPA可能是表征动脉对疾病敏感性的重要参数。

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