Composition of the endothelial glycocalyx and its relation to its thickness and diffusion of small solutes.
Composition of the endothelial glycocalyx and its relation to its thickness and diffusion of small solutes.
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DOI：
10.1016/j.mvr.2010.06.005
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发表时间：
2010-12
影响因子：
3.1
通讯作者：
Lipowsky HH
中科院分区：
文献类型：
--
作者：
Gao L;Lipowsky HH
内皮糖萼富含糖胺聚糖（GAGs）、硫酸肝素、硫酸软骨素和透明质酸。目前的研究旨在通过使用微移液管将肝素酶、软骨素酶和透明质酸酶注入大鼠肠系膜毛细血管后小静脉，直接酶解这些gag对糖萼层厚度和通透性的相对贡献进行评估。将酶去除导致的gag的相对损失与用10−7 M fMLP对肠系膜进行超灌注诱导的多糖的刺激脱落进行了比较。通过循环FITC标记70 kDa葡聚糖（Dx70）浸润糖萼，并测量染料前沿到内皮细胞表面的距离（EC）来评估糖萼的厚度，在对照条件下平均为463 nm。肝素酶、软骨素酶和透明质酸酶分别降低了43.3%、34.1%和26.1%，三种酶混合后分别降低了89.7%。采用一维扩散模型确定了FITC在糖萼中的扩散系数。通过将FITC弹体径向强度的实测瞬态与计算模型的瞬态进行比较，得到了扩散系数D。在酶注射和fMLP灌注前后，D值对应于Dx70 （DDx70）划定的层的厚度，以及EC表面上方173nm的较小亚层（D173）。DDx70的大小是D173的两倍，表明糖萼在EC表面附近更加致密。软骨素酶和透明质酸酶均显著升高DDx70和D173。然而，肝素酶降低了DDx70，而没有引起D173的任何显著变化。这些观察结果表明，这三种gag在糖萼中的分布并不均匀，它们对糖萼的通透性都有不同程度的贡献。fmlp诱导的脱落导致糖萼厚度减少（这可能会增加通透性），并且与肝素酶一样，降低溶质的扩散系数（这可能会降低通透性）。这种行为表明，去除硫酸乙酰肝素可能导致糖萼坍塌，通过压实层以保持恒定的过滤阻力来抵消厚度的减少。
The endothelial glycocalyx is well endowed with the glycosaminoglycans (GAGs) heparan sulfate, chondroitin sulfate and hyaluronan. The current studies aimed to assess the relative contributions of each of these GAGs to the thickness and permeability of the glycocalyx layer by direct enzymatic removal of each using micropipettes to infuse heparinase, chondroitinase and hyaluronidase into post-capillary venules of the intestinal mesentery of the rat. The relative losses of GAGs due to enzymatic removal were compared with stimulated shedding of glycans induced by superfusing the mesentery with 10−7 M fMLP. Thickness of the glycocalyx was assessed by infiltration of the glycocalyx with circulating FITC labeled 70 kDa dextran (Dx70) and measuring the distance from the dye front to the surface of the endothelium (EC), which averaged 463 nm under control conditions. Reductions in thickness were 43.3%, 34.1% and 26.1% following heparinase, chondroitinase and hyaluronidase, respectively, and 89.7% with a mixture of all three enzymes. Diffusion coefficients of FITC in the glycocalyx were determined using a 1-D diffusion model. By comparison of measured transients in radial intensity of a bolus of FITC with that of a computational model a diffusion coefficient D was obtained. Values of D were obtained corresponding to the thickness of the layer demarcated by Dx70 (DDx70), and a smaller sublayer 173 nm above the EC surface (D173), prior to and following enzyme infusion and superfusion with fMLP. The magnitude of DDx70 was twice that of D173 suggesting that the glycocalyx is more compact near the EC surface. Chondroitinase and hyaluronidase significantly increased both DDx70 and D173. However, heparinase decreased DDx70, and did not induce any significant change for the D173. These observations suggest that the three GAGs are not evenly distributed throughout the glycocalyx and that they each contribute to permeability of the glycocalyx to a differing extent. The fMLP-induced shedding caused a reduction in glycocalyx thickness (which may increase permeability) and as with heparinase, decreased the diffusion coefficient of solutes (which may decrease permeability). This behavior suggests that the removal of heparan sulfate may cause a collapse of the glycocalyx which counters decreases in thickness by compacting the layer to maintain a constant resistance to filtration.
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影响因子：
4.5
作者：
Reitsma, Sietze;Slaaf, Dick W.;Vink, Hans;van Zandvoort, Marc A. M. J.;Egbrink, Mirjam G. A. oude
通讯作者：
Egbrink, Mirjam G. A. oude
DOI：
10.1152/ajpheart.2001.280.3.h1051
发表时间：
2001-03-01
影响因子：
4.8
作者：
Constantinescu, AA;Vink, H;Spaan, JAE
通讯作者：
Spaan, JAE
DOI：
10.1073/pnas.96.9.4850
发表时间：
1999-04-27
影响因子：
11.1
作者：
Scott, JE;Heatley, F
通讯作者：
Heatley, F
DOI：
10.1152/ajpheart.00592.2005
发表时间：
2006-01-01
影响因子：
4.8
作者：
Gouverneur, M;Spaan, JAE;Vink, H
通讯作者：
Vink, H
影响因子：
7.8
作者：
RAPRAEGER, A
通讯作者：
RAPRAEGER, A