Protection of vascular barrier integrity by activated protein C in murine models depends on protease-activated receptor-1.

ABSTRACT: Protease activated receptor-1 (PAR1) mediates barrier protective signalling of activated protein C (APC) in human endothelial cells in vitro and may contribute to APC's beneficial effects in patients with severe sepsis. Mouse models are of key importance for translational research but species differences may limit conclusions for the human system. We analysed whether mouse APC can cleave, activate and induce signalling through murine PAR1 and tested in newly established mouse models if long-term infusion of APC prevents from vascular leakage. Cell surface immunoassays demonstrated efficient cleavage of endogenous murine endothelial PAR1 by either murine or human APC. Pharmacological concentrations of APC of either species had powerful barrier protective effects on cultured murine endotheli

SUBMITTER: Schuepbach RA 

PROVIDER: S-EPMC2680237 | biostudies-literature | 2009 Apr

REPOSITORIES: biostudies-literature