Endothelial glycocalyx breakdown is mediated by angiopoietin-2

被引:115
作者
Lukasz, Alexander [1 ,2 ]
Hillgruber, Carina [3 ]
Oberleithner, Hans [2 ]
Kusche-Vihrog, Kristina [2 ]
Pavenstadt, Hermann [1 ]
Rovas, Alexandros [1 ]
Hesse, Bettina [1 ,2 ]
Goerge, Tobias [3 ]
Kumpers, Philipp [1 ]
机构
[1] Univ Hosp Munster, Div Gen Internal Med Nephrol & Rheumatol, Dept Med D, Albert Schweitzer Campus 1, D-48149 Munster, Germany
[2] Univ Hosp Munster, Inst Physiol 2, Robert Koch Str 27b, D-48149 Munster, Germany
[3] Univ Hosp Munster, Dept Dermatol, Von Esmarch Str 58, D-48149 Munster, Germany
关键词
Angiopoietin-2; Endothelial activation; Glycocalyx; Miles assay; Heparanase; ACTIN CYTOSKELETON; INDUCED INCREASE; CELL-ADHESION; SURFACE-LAYER; TNF-ALPHA; IN-VIVO; BARRIER; DYSFUNCTION; ACTIVATION; HEPARANASE;
D O I
10.1093/cvr/cvx023
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:671 / 680
页数:10
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