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Coupling of thrombin-PAR1 and EPCR/PC-PAR1 signaling to barrier-regulating S1P receptor subtypes. In vitro studies indicated that thrombin-induced S1P3 activation promotes vascular leakage, whereas aPC-mediated S1P1 cross activation can diminish vascular leak and enhances barrier protection. S1P3 is also required for LPS-induced vascular leakage.
