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Blood, 1 February 2007, Vol. 109, No. 3, pp. 1003-1009. Prepublished online as a Blood First Edition Paper on October 5, 2006; DOI 10.1182/blood-2006-06-032086. This Article Full Text (PDF) All Versions of this Article: blood-2006-06-032086v1 109/3/1003    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Zheng, X. Articles by Esmon, C. T. Search for Related Content PubMed PubMed Citation Articles by Zheng, X. Articles by Esmon, C. T. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 28, 2006 Accepted September 14, 2006 Effects of membrane and soluble EPCR on the hemostatic balance and endotoxemia in mice Xunzhen Zheng, Weihong Li, Jian-Ming Gu, Dongfeng Qu, Gary L. Ferrell, Naomi L. Esmon, and Charles T. Esmon* Oklahoma Medical Research Foundation, the Howard Hughes Medical Institute, United States Berlex Biosciences, United States University of Oklahoma Health Sciences Center, United States * Corresponding author; email: esmonc{at}omrf.ouhsc.edu. Recent studies have shown that endothelial protein C receptor (EPCR) polymorphisms and soluble EPCR levels are associated with thrombotic diseases. It is unknown whether membrane EPCR (mEPCR) heterozygosity and/or physiologically elevated sEPCR levels directly impact the hemostatic balance and the outcome of endotoxemia. In these studies, thrombin infusion experiments revealed that EPCR heterozygosity (Procr +/-) impaired protein C activation approximately 30%. Infusion of factor Xa with phopholipid demonstrated that the Procr +/- genotype increased the coagulant response relative to wild type mice. Challenge of the Procr +/- mice with lipopolysaccharide (LPS) did not significantly exaggerate their response compared to wild type mice. We also generated mice in which one allele of full length EPCR was replaced by sEPCR (Procr s/+). Compared to Procr +/- mice, Procr s/+ mice had 5 fold higher sEPCR and similar mEPCR levels. Procr +/- and Procr s/+ mice generated similar levels of APC upon thrombin infusion. They also exhibited a similar coagulant response upon factor Xa/phospholipid infusion. Only supra-physiological levels of sEPCR could influence protein C activation and exaggerate the coagulant response. In conclusion, mEPCR, but not physiologically elevated sEPCR, regulated protein C activation. Procr heterozygosity results in a mild increase of thrombosis tendency and little influence on the response to endotoxin. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: F. Niessen, C. Furlan-Freguia, J. A. Fernandez, L. O. Mosnier, F. J. Castellino, H. Weiler, H. Rosen, J. H. Griffin, and W. Ruf Endogenous EPCR/aPC-PAR1 signaling prevents inflammation-induced vascular leakage and lethality Blood, March 19, 2009; 113(12): 2859 - 2866. [Abstract] [Full Text] [PDF] E. J. Kerschen, J. A. Fernandez, B. C. Cooley, X. V. Yang, R. Sood, L. O. Mosnier, F. J. Castellino, N. Mackman, J. H. Griffin, and H. Weiler Endotoxemia and sepsis mortality reduction by non-anticoagulant activated protein C J. Exp. Med., October 1, 2007; 204(10): 2439 - 2448. [Abstract] [Full Text] [PDF]

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