Division of Nephrology, Department of Medicine, Academic Medical Center, A01-132, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
J Am Soc Nephrol. 2012 Nov;23(11):1900-8. doi: 10.1681/ASN.2011121181. Epub 2012 Oct 18.
Damage to the endothelial glycocalyx, which helps maintain vascular homeostasis, heightens the sensitivity of the vasculature to atherogenic stimuli. Patients with renal failure have endothelial dysfunction and increased risk for cardiovascular morbidity and mortality, but the state of the endothelial glycocalyx in these patients is unknown. Here, we used Sidestream Darkfield imaging to detect changes in glycocalyx dimension in dialysis patients and healthy controls from in vivo recordings of the sublingual microcirculation. Dialysis patients had increased perfused boundary region and perfused diameters, consistent with deeper penetration of erythrocytes into glycocalyx, indicating a loss of glycocalyx barrier properties. These patients also had higher serum levels of the glycocalyx constituents hyaluronan and syndecan-1 and increased hyaluronidase activity, suggesting the shedding of these components. Loss of residual renal function had no influence on the imaging parameters but did associate with greater shedding of hyaluronan in blood. Furthermore, patients with higher levels of inflammation had more significant damage to the glycocalyx barrier. In conclusion, these data suggest that dialysis patients have an impaired glycocalyx barrier and shed its constituents into blood, likely contributing to the sustained endothelial cell activation observed in ESRD.
内皮糖萼的损伤有助于维持血管内稳态，增加了血管对动脉粥样硬化刺激的敏感性。肾衰竭患者存在内皮功能障碍，心血管发病率和死亡率增加，但这些患者的内皮糖萼状态尚不清楚。在这里，我们使用边流暗场成像技术，从舌下微循环的体内记录中，检测透析患者和健康对照组中糖萼尺寸的变化。透析患者的灌注边界区域和灌注直径增加，这与红细胞更深地渗透到糖萼中一致，表明糖萼屏障特性丧失。这些患者的血清糖萼成分透明质酸和 syndecan-1 水平也较高，透明质酸酶活性增加，表明这些成分的脱落。残余肾功能的丧失对成像参数没有影响，但与血液中透明质酸的脱落增加有关。此外，炎症水平较高的患者，糖萼屏障的损伤更严重。总之，这些数据表明，透析患者的糖萼屏障受损，并将其成分脱落到血液中，这可能是 ESRD 中观察到的持续内皮细胞激活的原因。
