Unknown

Dataset Information

0

Peptide Bbeta(15-42) preserves endothelial barrier function in shock.


ABSTRACT: 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 Bbeta15-42 (also called FX06), significantly reduces vascular leak and mortality in animal models for Dengue shock syndrome. The ability of Bbeta15-42 to preserve endothelial barriers is confirmed in rats i.v.-injected with LPS. In endothelial cells, Bbeta15-42 prevents thrombin-induced stress fiber formation, myosin light chain phosphorylation and RhoA activation. The molecular key for the protective effect of Bbeta15-42 is the src kinase Fyn, which associates with VE-cadherin-containing junctions. Following exposure to Bbeta15-42 Fyn dissociates from VE-cadherin and associates with p190RhoGAP, a known antagonists of RhoA activation. The role of Fyn in transducing effects of Bbeta15-42 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 Bbeta15-42. 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.

SUBMITTER: Groger M 

PROVIDER: S-EPMC2670535 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC7274136 | biostudies-literature
| S-EPMC7011568 | biostudies-literature
2022-05-19 | PXD030300 | Pride
| S-EPMC4701557 | biostudies-literature
| S-EPMC9576825 | biostudies-literature
| S-EPMC3158721 | biostudies-literature
| S-EPMC10907362 | biostudies-literature
| S-EPMC7865261 | biostudies-literature
| S-EPMC6171817 | biostudies-other
| S-EPMC6866681 | biostudies-literature