Hemodynamic shear stress characteristic of atherosclerosis-resistant regions promotes glycocalyx formation in cultured endothelial cells
Hemodynamic shear stress characteristic of atherosclerosis-resistant regions promotes glycocalyx formation in cultured endothelial cells
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DOI：
10.1152/ajpcell.00187.2012
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发表时间：
2013-01-01
影响因子：
5.5
通讯作者：
Garcia-Cardena, Guillermo
中科院分区：
文献类型：
--
作者：
Koo, Andrew;Dewey, C. Forbes, Jr.;Garcia-Cardena, Guillermo
Koo A，Dewey CF Jr，Garcia-Carde a G。动脉粥样硬化抗性区域的血流动力学剪切应力特征促进培养内皮细胞中糖萼的形成。 Am J Physiol Cell Physiol 304：C137-C146，2013。首次发表于 2012 年 10 月 31 日； doi:10.1152/ajpcell.00187.2012.-内皮糖萼是位于血管内皮细胞顶端表面的糖胺聚糖层，已被证明对多种内皮功能很重要。先前的研究已经证明，小鼠颈总动脉区域的糖萼含量很高，该区域的内皮细胞暴露于层流剪切应力，并且能够抵抗动脉粥样硬化。相比之下，小鼠颈内动脉窦区域的糖萼稀少或不存在，该区域暴露于非层流剪切应力并且极易发生动脉粥样硬化。基于这些观察，我们假设内皮糖萼成分的表达受到不同血流动力学环境的差异调节。为了检验这一假设，将人内皮细胞暴露于人颈动脉抗动脉粥样硬化或动脉粥样硬化易感区域的剪切应力波形中，并评估糖萼的几种成分的表达。这些实验表明，内皮糖萼的几种成分的表达受到不同剪切应力波形的差异调节。有趣的是，我们发现硫酸乙酰肝素表达增加并均匀分布在暴露于动脉粥样硬化波形的内皮细胞的顶端表面上，并且不规则地存在于暴露于动脉粥样硬化波形的细胞中。此外，硫酸乙酰肝素蛋白多糖 Syndecan-1 的表达也受到两种波形的差异调节，并且其抑制会减弱硫酸乙酰肝素的动脉粥样硬化流动诱导的细胞表面表达。总的来说，这些数据将不同的血流动力学环境与内皮糖萼关键成分的差异表达联系起来。
Koo A, Dewey CF Jr, Garcia-Carde a G. Hemodynamic shear stress characteristic of atherosclerosis-resistant regions promotes glycocalyx formation in cultured endothelial cells. Am J Physiol Cell Physiol 304: C137-C146, 2013. First published October 31, 2012; doi:10.1152/ajpcell.00187.2012.-The endothelial glycocalyx, a glycosaminoglycan layer located on the apical surface of vascular endothelial cells, has been shown to be important for several endothelial functions. Previous studies have documented that the glycocalyx is highly abundant in the mouse common carotid region, where the endothelium is exposed to laminar shear stress, and it is resistant to atherosclerosis. In contrast, the glycocalyx is scarce or absent in the mouse internal carotid sinus region, an area exposed to nonlaminar shear stress and highly susceptible to atherosclerosis. On the basis of these observations, we hypothesized that the expression of components of the endothelial glycocalyx is differentially regulated by distinct hemodynamic environments. To test this hypothesis, human endothelial cells were exposed to shear stress waveforms characteristic of atherosclerosis-resistant or atherosclerosis-susceptible regions of the human carotid, and the expression of several components of the glycocalyx was assessed. These experiments revealed that expression of several components of the endothelial glycocalyx is differentially regulated by distinct shear stress waveforms. Interestingly, we found that heparan sulfate expression is increased and evenly distributed on the apical surface of endothelial cells exposed to the atheroprotective waveform and is irregularly present in cells exposed to the atheroprone waveform. Furthermore, expression of a heparan sulfate proteoglycan, syndecan-1, is also differentially regulated by the two waveforms, and its suppression mutes the atheroprotective flow-induced cell surface expression of heparan sulfate. Collectively, these data link distinct hemodynamic environments to the differential expression of critical components of the endothelial glycocalyx.