| First Author | Lukasz A | Year | 2017 |
| Journal | Cardiovasc Res | Volume | 113 |
| Issue | 6 | Pages | 671-680 |
| PubMed ID | 28453727 | Mgi Jnum | J:258885 |
| Mgi Id | MGI:6141854 | Doi | 10.1093/cvr/cvx023 |
| Citation | Lukasz A, et al. (2017) Endothelial glycocalyx breakdown is mediated by angiopoietin-2. Cardiovasc Res 113(6):671-680 |
| abstractText | 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. |
