To be or not to be protease activated receptor-1 in activated protein C-initiated endothelial barrier protection 英文参考文献.docVIP

Available online /content/11/1/407 Letter To be or not to be protease activated receptor-1 in activated protein C-initiated endothelial barrier protection? Shi-Sheng Li Department of Molecular Experimental Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA Corresponding author: Shi-Sheng Li, sshli@ Published: 19 February 2007 Critical Care 2007, 11:407 (doi:10.1186/cc5149) This article is online at /content/11/1/407 ? 2007 BioMed Central Ltd See related review by Looney and Matthay, /content/10/6/239 The review by Looney and Matthay summarized recent progress in basic and preclinical research of activated protein C (APC), a novel therapeutic agent for the treatment of severe sepsis [1]. APC is traditionally an anticoagulant and profibrinolytic agent, and has been appreciated to possess anti-inflammatory and anti-apoptotic properties, yet the exact mechanisms by which APC executes its clinical effects in sepsis are not defined [2]. Emerging evidence has suggested that APC might exert its clinical benefit, at least in part, by maintaining endothelial barrier function [3,4]. The authors reviewed conflicting results of endothelial barrier protection of APC in the literature and pointed out that caution must be Looney and Matthay stated that ‘in two different in vitro investigations [3,4], APC promoted endothelial barrier protection in a PAR-1- and S1P1-dependent mechanism’, which represents a misinterpretation. These two papers did conclude that APC enhanced endothelial barrier function in different cell lines by a sphingosine 1-phosphate receptor-1 (S1P1)-dependent signaling pathway, but it is still arguable whether this is protease activated receptor-1 (PAR-1) dependent. Finigan and colleagues showed that anti-PAR-1 blocking antibody did not interfere with eithe