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- Title
Endothelial glycocalyx breakdown is mediated by angiopoietin-2.
- Authors
Lukasz, Alexander; Hillgruber, Carina; Oberleithner, Hans; Kusche-Vihrog, Kristina; Pavenstädt, Hermann; Rovas, Alexandros; Hesse, Bettina; Goerge, Tobias; Kümpers, Philipp
- Abstract
Aims 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. Methods and results 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. Conclusion Our data indicate that eGC breakdown is mediated by Angpt-2 in a non-redundant manner.
- Subjects
GLYCOCALYX; ANGIOPOIETIN-2; HEPARANASE; ENZYME analysis; ENDOTOXIN analysis
- Publication
Cardiovascular Research, 2017, Vol 113, Issue 6, p671
- ISSN
0008-6363
- Publication type
Article
- DOI
10.1093/cvr/cvx023