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Alexander Lukasz, Carina Hillgruber, Hans Oberleithner, Kristina Kusche-Vihrog, Hermann Pavenstädt, Alexandros Rovas, Bettina Hesse, Tobias Goerge, Philipp Kümpers, Endothelial glycocalyx breakdown is mediated by angiopoietin-2, Cardiovascular Research, Volume 113, Issue 6, 1 May 2017, Pages 671–680, https://doi.org/10.1093/cvr/cvx023
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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.