The role of endothelial glycocalyx components in mechanotransduction of fluid shear stress

The role of endothelial glycocalyx components in mechanotransduction of fluid shear stress
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DOI:
10.1016/j.bbrc.2007.01.137
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发表时间:
2007-03-30
影响因子:
3.1
通讯作者:
Tarbell, John M.
Tarbell, John M.
中科院分区:
生物学4区
文献类型:
--
作者:
Pahakis, Manolis Y.;Kosky, Jason R.;Tarbell, John M.

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内皮细胞的表面装饰有各种各样的膜结合的大分子,构成糖萼。这些包括带有末端唾液酸(SA)的酸性寡糖的糖蛋白,以及与其相关的糖胺聚糖的蛋白聚糖,所述糖胺聚糖包括:硫酸乙酰肝素(HS)、硫酸软骨素(CS)和透明质酸(HA)。在这项研究中,酶被用来选择性地降解牛主动脉内皮细胞表面的糖萼成分,并确定这些改变对流体剪切诱导的一氧化氮(NO)和前列环素(PGI(2))产生的影响。耗尽HS,HA和SA,但不CS,阻断剪切诱导的NO产生。令人惊讶的是,阻断NO产生的相同酶的消耗对剪切诱导的PGI(2)产生没有影响。结果可以解释为剪切诱导的NO转导的磷脂酰肌醇蛋白聚糖-小窝-eNOS机制,PGI(2)在基底粘附斑块中转导,无论糖萼是否完整,基底粘附斑块都能感受到相同的反应应激。(c)2007年爱思唯尔公司All rights reserved.
The surface of endothelial cells is decorated with a wide variety of membrane-bound macromolecules that constitute the glycocalyx. These include glycoproteins bearing acidic oligosaccharides with terminal sialic acids (SA), and proteoglycans with their associated glycosaminoglycan that include: heparan sulfate (HS), chondroitin sulfate (CS), and hyaluronic acid (HA). In this study, enzymes were used to selectively degrade glycocalyx components from the surface of bovine aortic endothelial cells and the effects of these alterations on fluid shear-induced nitric oxide (NO) and prostacyclin (PGI(2)) production were determined. Depletion of HS, HA, and SA, but not CS, blocked shear-induced NO production. Surprisingly, the same enzyme depletions that blocked NO production had no influence on shear-induced PGI(2) production. The results may be interpreted in terms of a glypican-caveolae-eNOS mechanism for shear-induced NO transduction, with PGI(2) being transduced in basal adhesion plaques that sense the same reaction stress whether the glycocalyx is intact or not. (c) 2007 Elsevier Inc. All rights reserved.