Department of Medicine D, Division of General Internal Medicine, Nephrology, and Rheumatology, University Hospital Münster, Albert-Schweitzer-Campus 1, 48149 Münster, Germany.
Institute of Physiology II, University Hospital Münster, Robert-Koch-Straße 27b, 48149 Münster, Germany.
Cardiovasc Res. 2017 May 1;113(6):671-680. doi: 10.1093/cvr/cvx023.
The endothelial glycocalyx (eGC), a carbohydrate-rich layer lining the luminal surface of the endothelium, provides a first vasoprotective barrier against vascular leakage and adhesion in sepsis and vessel inflammation. Angiopoietin-2 (Angpt-2), an antagonist of the endothelium-stabilizing receptor Tie2 secreted by endothelial cells, promotes vascular permeability through cellular contraction and junctional disintegration. We hypothesized that Angpt-2 might also mediate the breakdown of the eGC.
Using confocal and atomic force microscopy, we show that exogenous Angpt-2 induces a rapid loss of the eGC in endothelial cells in vitro. Glycocalyx deterioration involves the specific loss of its main constituent heparan sulphate, paralleled by the secretion of the heparan sulphate-specific heparanase from late endosomal/lysosomal stores. Corresponding in vivo experiments revealed that exogenous Angpt-2 leads to heparanase-dependent eGC breakdown, which contributes to plasma leakage and leukocyte recruitment in vivo.
Our data indicate that eGC breakdown is mediated by Angpt-2 in a non-redundant manner.
血管内皮糖萼（eGC）是一种富含碳水化合物的层，位于内皮的腔面，为血管渗漏和黏附提供第一道血管保护屏障，在脓毒症和血管炎症中发挥作用。血管生成素-2（Angpt-2）是内皮细胞分泌的内皮稳定受体 Tie2 的拮抗剂，通过细胞收缩和连接解体促进血管通透性。我们假设 Angpt-2 也可能介导 eGC 的破坏。
使用共聚焦和原子力显微镜，我们显示外源性 Angpt-2 在体外诱导内皮细胞中 eGC 的快速丢失。糖萼恶化涉及其主要成分硫酸乙酰肝素的特异性丧失，同时来自晚期内体/溶酶体储存的硫酸乙酰肝素特异性肝素酶分泌。相应的体内实验表明，外源性 Angpt-2 导致肝素酶依赖性 eGC 破坏，这有助于体内的血浆渗漏和白细胞募集。
我们的数据表明，eGC 的破坏是由 Angpt-2 介导的，这是一种非冗余的方式。
