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Identification of functional endothelial protein C receptor in human plasma.
Open accessAbstract
The endothelial cell protein C receptor (EPCR) binds protein C and facilitates activation by the thrombin-thrombomodulin complex. EPCR also binds activated protein C (APC) and inhibits APC anticoagulant activity. In this study, we detected a soluble form of EPCR in normal human plasma. Plasma EPCR appears to be approximately 43, 000 D, and circulates at approximately 100 ng/ml (98.4+/-27.8 ng/ml, n = 22). Plasma EPCR was purified from human citrated plasma using ion exchange, immunoaffinity, and protein C affinity chromatography. Flow cytometry experiments demonstrated that plasma EPCR bound APC with an affinity similar to that previously determined for recombinant soluble EPCR (Kdapp = 30 nM). Furthermore, plasma EPCR inhibited both protein C activation on an endothelial cell line and APC anticoagulant activity in a one-stage Factor Xa clotting assay. The physiological function of plasma EPCR is uncertain, but if the local concentrations are sufficiently high, particularly in disease states, the present data suggest that the soluble plasma EPCR could attenuate the membrane-bound EPCR augmentation of protein C activation and the anticoagulant function of APC.
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“Research has shown that soluble EPCR impairs the activation of protein C. 58”
From Meta-analysis of ACE inhibitor-induced angioedema identifies novel risk locus. (2024) · cites this paper as [58]
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Metadata
- Authors
- Kurosawa, S., Stearns-Kurosawa, D. J., Hidari, N., & Esmon, C. T.
- Affiliations
- Oklahoma Medical Research Foundation (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Esmon, C T
- Venue
- Journal of Clinical Investigation
- Published
- 1997-07-15
- Volume
- 100
- Issue
- 2
- Pages
- 411-418
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC508205
- OpenAlex
- W1993601122
- Cited by
- 154
- References
- 50
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 1 · 2022: 3 · 2021: 2 · 2020: 2 · 2017: 3 · 2016: 8 · 2015: 8 · 2014: 13 · 2013: 16 · 2012: 2
- FWCI
- 3.66
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health (P50 HL54502)
- National Heart, Lung, and Blood Institute (P50HL054502, P01 HL54804, P50-HL54502, P01HL054804)
- Topics
- Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
- Life Sciences › Immunology and Microbiology › Immunology › Complement system in diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Keywords
- endothelial protein C receptor, soluble EPCR, activated protein C, protein C activation, anticoagulant activity, thrombin-thrombomodulin complex, plasma protein purification, endothelial cells
- MeSH terms
- Anticoagulants, Blood Coagulation, Blood Coagulation Factors, Cells, Cultured, Chromatography, Affinity, Endothelium, Vascular, Flow Cytometry, Humans, Protein Binding, Protein C, Receptors, Cell Surface, Recombinant Proteins, Solubility, Thrombin, Blotting, Western, Factor Xa, Thrombomodulin
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