The Interaction between Fluid Wall Shear Stress and Solid Circumferential Strain Affects Endothelial Gene Expression.

The Interaction between Fluid Wall Shear Stress and Solid Circumferential Strain Affects Endothelial Gene Expression.
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DOI:
10.1371/journal.pone.0129952
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发表时间:
2015
期刊:
影响因子:
3.7
通讯作者:
Tarbell JM
Tarbell JM
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Amaya R;Pierides A;Tarbell JM

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内衬血管壁的内皮细胞同时暴露于壁剪切应力(WSS)和周向应力(CS),其可以通过WSS和CS之间的时间相位角(应力相位角- SPA)来表征。具有高度异步血流动力学(SPA接近-180°)的循环区域(例如冠状动脉)与病理状况(例如动脉粥样硬化和内膜增生)的发展相关,而更同步的区域(SPA接近0°)免于疾病。本研究评估了在非同步血流动力学(SPA=-180 °)和同步血流动力学(SPA=0 °)下42个动脉粥样硬化相关基因的内皮细胞基因表达。本研究采用一种新型生物反应器,研究了牛主动脉内皮细胞(BAECS)在SPA=0或SPA=-180时暴露于脉动WSS和CS组合的细胞反应。使用42个基因的PCR阵列,我们确定了在7小时的测试期内暴露于非逆转正弦WSS(10±10 dyne/cm 2)和CS(4 ± 4%)的BAECS显示出17个基因被SPA = -180 °上调,其中大多数是促动脉粥样硬化的,包括NFκB和其他NFκB靶基因。Western blot和免疫荧光染色证实SPA =-180°上调NFκ B p50/p105和p65,表明NFκB p50/p105和p65发生核转位。这些数据表明,与无剪切应力逆转的同步血流动力学相比,异步血流动力学(SPA=-180 °)可引起内皮细胞的促动脉粥样硬化反应,表明SPA可能是表征动脉对疾病易感性的重要参数。
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.
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