Firewall function of the endothelial glycocalyx in the regulation of sodium homeostasis
Firewall function of the endothelial glycocalyx in the regulation of sodium homeostasis
复制标题
DOI：
10.1007/s00424-011-1038-y
复制
发表时间：
2012-02-01
影响因子：
4.5
通讯作者：
Kusche-Vihrog, Kristina
中科院分区：
文献类型：
--
作者：
Korte, Stefanie;Wiesinger, Anne;Kusche-Vihrog, Kristina
在醛固酮存在的情况下，血浆钠略高于正常水平，会使血管内皮细胞变硬，并减少一氧化氮的释放，从而导致内皮功能障碍。这一过程是由上皮性钠通道(ENaC)和最可能的内皮Na+/K+-ATPase介导的。ENaC和Na+/K+-ATPase均定位于内皮细胞的质膜，并嵌入内皮细胞的糖基化产物(EGC)中。这种带负电荷的生物聚合物直接暴露在血流中，并选择性地缓冲钠离子。我们假设，当细胞外钠在生理范围内变化时，糖萼可能会干扰内皮钠的运输。因此，我们将内皮细胞建模为一个泵-泄漏系统，测量培养的人内皮细胞内钠离子的变化。实验分别在酶法去除EGC前后的低/高胞外钠条件下进行，并分别抑制Na+/K+-ATPase和ENaC。主要观察到三个方面：(1)肝素酶对EGC的清除促进了钠进入/退出内皮细胞。(2)Na+/K+-ATPase和ENaC活性受细胞外钠离子浓度的影响，钠离子在血管内皮细胞膜上的运动方向与细胞外钠离子浓度有关。(3)EGC的清除和钠转运的抑制改变了内皮细胞的电阻。我们得出结论，EGC是一种潜在的“防火墙”，可以阻止钠不受控制地进入内皮细胞的泵-渗漏系统。去除EGC后，钠更容易进入系统。因此，泵-漏系统可以在病理生理条件下受环境钠的调节，控制血管的通透性。
Plasma sodium, slightly above normal and in presence of aldosterone, stiffens vascular endothelium and reduces nitric oxide release with the consequence of endothelial dysfunction. This process is mediated by epithelial sodium channels (ENaC) and, most likely, the endothelial Na+/K+-ATPase. Both, ENaC and Na+/K+-ATPase, are located in the plasma membrane of endothelial cells and embedded in the endothelial glycocalyx (eGC). This negatively charged biopolymer is directly exposed to the blood stream and selectively buffers sodium ions. We hypothesize that the glycocalyx could interfere with endothelial sodium transport when extracellular sodium varies in the physiological range. Therefore, we modeled the endothelial cell as a pump-leak system measuring changes of intracellular sodium in cultured human endothelial cells. Experiments were performed under low/high extracellular sodium conditions before and after enzymatic eGC removal, and with inhibition of Na+/K+-ATPase and ENaC, respectively. Three major observations were made: (1) eGC removal by heparinase treatment facilitates sodium to enter/exit the endothelial cells. (2) The direction of net sodium movement across the endothelial plasma membrane depends on the concentration of extracellular sodium which regulates both the Na+/K+-ATPase and ENaC activity. (3) Removal of eGC and inhibition of sodium transport modify the electrical resistance of endothelial cells. We conclude that the eGC serves as a potential "firewall" preventing uncontrolled access of sodium to the pump-leak system of the endothelial cell. After eGC removal, sodium access to the system is facilitated. Thus the pump-leak system could be regulated by ambient sodium and control vascular permeability in pathophysiological conditions.