Proteolytic Activity Attenuates the Response of Endothelial Cells to Fluid Shear Stress.
Proteolytic Activity Attenuates the Response of Endothelial Cells to Fluid Shear Stress.
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DOI：
10.1007/s12195-011-0207-6
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发表时间：
2012-03
影响因子：
2.8
通讯作者：
Schmid-Schoenbein, Geert W.
中科院分区：
文献类型：
--
作者：
Altshuler, Angelina E.;Morgan, Mary J.;Chien, Shu;Schmid-Schoenbein, Geert W.
最近的证据表明，几种实验病理生理条件与血浆中蛋白酶活性升高有关，从而影响内皮功能。我们假设，与内皮细胞（EC）膜结合的细胞外结构可能被蛋白水解活性降解，导致细胞对生理剪切应力（12 dyn/cm2）产生异常反应。为了验证这一假设，培养的牛主动脉内皮细胞（BAECs）暴露于低水平的丝氨酸蛋白酶，胰蛋白酶。测定糖萼和血管内皮生长因子受体2 （VEGFR-2）的细胞外机械传感器密度。通过检查胰岛素受体和葡萄糖摄取水平来检测代谢功能障碍。在剪切应力作用12小时后，蛋白酶抑制了细胞沿流体流动方向排列的能力；然而，在蛋白酶抑制的剪切应力下，细胞在额外的12小时后重新排列。在静态和剪切条件下，蛋白酶导致糖萼、VEGFR-2和胰岛素受体的密度降低，但静态VEGFR-2细胞除外。在静态条件下，与未处理的对照组相比，蛋白酶处理的内皮细胞葡萄糖摄取减少。然而，在剪切作用下，蛋白酶处理的baec的葡萄糖摄取大于未处理的对照组。总之，血浆中的蛋白酶活性改变了内皮细胞的外表面膜成分，并可能干扰机械转导。
Recent evidence indicates that several experimental pathophysiological conditions are associated with elevated protease activity in plasma, which impacts endothelial function. We hypothesize that extracellular structures bound to the endothelial cell (EC) membrane may be degraded by proteolytic activity and cause the cells to respond abnormally to physiological shear stress (12 dyn/cm2). To test this hypothesis, cultured bovine aortic endothelial cells (BAECs) were exposed to low levels of a serine protease, trypsin. Extracellular mechanosensor densities of the glycocalyx and vascular endothelial growth factor receptor 2 (VEGFR-2) were determined. Metabolic dysfunction was tested by examining insulin receptor and glucose uptake levels. Protease treatment impaired the cells’ ability to align in the direction of fluid flow after 12 hours of shear stress; however, cells realigned after an additional 12 hours of shear stress with protease inhibition. Proteases caused reduction in the densities of glycocalyx, VEGFR-2, and insulin receptor in static and shear conditions, except for static VEGFR-2 cells. Under static conditions, protease-treated endothelial cells had reduced glucose uptake compared to untreated controls. Under shear, however, glucose uptake for protease-treated BAECs was greater than untreated controls. In conclusion, protease activity in plasma alters the exofacial membrane components of ECs and may interfere with mechanotransduction.
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影响因子：
7.3
作者：
Masini, Emanuela;Cuzzocrea, Salvatore;Bani, Daniele
通讯作者：
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影响因子：
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作者：
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影响因子：
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作者：
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通讯作者：
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DOI：
10.1152/ajpheart.00786.2003
发表时间：
2004-05-01
影响因子：
4.8
作者：
Cho, CH;Lee, CS;Koh, GY
通讯作者：
Koh, GY