TY  - JOUR
A1  - Gröger, Marion
A1  - Pasteiner, Waltraud
A1  - Ignatyev, George
A1  - Matt, Ulrich
A1  - Knapp, Sylvia
A1  - Atrasheuskaya, Alena
A1  - Bukin, Eugenij
A1  - Friedl, Peter
A1  - Zinkl, Daniela
A1  - Hofer-Warbinek, Renate
A1  - Zacharowski, Kai
A1  - Petzelbauer, Peter
A1  - Reingruber, Sonja
T1  - Peptide Bbeta(15-42) preserves endothelial barrier function in shock
T2  - PLoS One
N2  - Loss of vascular barrier function causes leak of fluid and proteins into tissues, extensive leak leads to shock and death. Barriers are largely formed by endothelial cell-cell contacts built up by VE-cadherin and are under the control of RhoGTPases. Here we show that a natural plasmin digest product of fibrin, peptide Bß15-42 (also called FX06), significantly reduces vascular leak and mortality in animal models for Dengue shock syndrome. The ability of Bß15-42 to preserve endothelial barriers is confirmed in rats i.v.-injected with LPS. In endothelial cells, Bß15-42 prevents thrombin-induced stress fiber formation, myosin light chain phosphorylation and RhoA activation. The molecular key for the protective effect of Bß15-42 is the src kinase Fyn, which associates with VE-cadherin-containing junctions. Following exposure to Bß15-42 Fyn dissociates from VE-cadherin and associates with p190RhoGAP, a known antagonists of RhoA activation. The role of Fyn in transducing effects of Bß15-42 is confirmed in Fyn -/- mice, where the peptide is unable to reduce LPS-induced lung edema, whereas in wild type littermates the peptide significantly reduces leak. Our results demonstrate a novel function for Bß15-42. Formerly mainly considered as a degradation product occurring after fibrin inactivation, it has now to be considered as a signaling molecule. It stabilizes endothelial barriers and thus could be an attractive adjuvant in the treatment of shock.
Y1  - 2009
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/7332
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30-73121
SN  - 1932-6203
N1  - Copyright Gröger et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
VL  - 4
IS  - (4): e5391
ER  -