Department of Physiology, The Ruth & Bruce Rappaport Faculty of Medicine, Technion-Israeli Institute of Technology, Haifa, Israel; Laboratory Medicine, Rambam Health Campus, Haifa, Israel.
Department of Nephrology, Nazareth Hospital, Nazareth, Azrieli Faculty of Medicine-Bar Ilan University, Jerusalem, Israel.
Am J Pathol. 2020 Apr;190(4):752-767. doi: 10.1016/j.ajpath.2019.08.019. Epub 2020 Feb 6.
The glycocalyx is a layer coating the luminal surface of vascular endothelial cells. It is vital for endothelial function as it participates in microvascular reactivity, endothelium interaction with blood constituents, and vascular permeability. Structural and functional damage to glycocalyx occurs in various disease states. A prominent clinical situation characterized by glycocalyx derangement is ischemia-reperfusion (I/R) of the whole body as well as during selective I/R to organs such as the kidney, heart, lung, or liver. Degradation of the glycocalyx is now considered a cornerstone in I/R-related endothelial dysfunction, which further impairs local microcirculation with a feed-forward loop of organ damage, due to vasoconstriction, leukocyte adherence, and activation of the immune response. Glycocalyx damage during I/R is evidenced by rising plasma levels of its principal constituents, heparan sulfate and syndecan-1. By contrast, the concentrations of these compounds in the circulation decrease after successful protective interventions in I/R, suggesting their use as surrogate biomarkers of endothelial integrity. In light of the importance of the glycocalyx in preserving endothelial cell integrity and its involvement in pathologic conditions, several promising therapeutic strategies to restore the damaged glycocalyx and to attenuate its deleterious consequences have been suggested. This review focuses on alterations of glycocalyx during I/R injury in general (to vital organs in particular), and on maneuvers aimed at glycocalyx recovery during I/R injury.
糖萼是覆盖血管内皮细胞腔面的一层。它对于内皮功能至关重要,因为它参与微血管反应性、内皮与血液成分的相互作用以及血管通透性。糖萼的结构和功能损伤发生在各种疾病状态中。一种以糖萼紊乱为特征的突出临床情况是全身缺血再灌注(I/R),以及在肾脏、心脏、肺或肝脏等器官的选择性 I/R 中。糖萼的降解现在被认为是与 I/R 相关的内皮功能障碍的基石,由于血管收缩、白细胞黏附和免疫反应的激活,进一步损害局部微循环,形成器官损伤的正反馈循环。I/R 期间糖萼损伤的证据是其主要成分肝素硫酸盐和 syndecan-1 的血浆水平升高。相比之下,在 I/R 中成功进行保护干预后,这些化合物在循环中的浓度降低,表明它们可用作内皮完整性的替代生物标志物。鉴于糖萼在维持内皮细胞完整性中的重要性及其在病理状况中的参与,已经提出了几种有前途的治疗策略来恢复受损的糖萼并减轻其有害后果。这篇综述重点介绍了一般情况下 I/R 损伤过程中糖萼的变化(特别是对重要器官),以及旨在恢复 I/R 损伤期间糖萼的操作。