Research Topics
| C EsmonSummaryAffiliation: University of Oklahoma Health Sciences Center Country: USA Publications
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Detail Information
Publications
Valves of the deep venous system: an overlooked risk factorErin G Brooks
Department of Pathology, University of Vermont, Burlington, VT 05482, USA
Blood 114:1276-9. 2009..001; for VWF, P = .01). These data support our hypothesis and suggest that variation in valvular sinus thromboresistance may be an important factor in venous thrombogenesis...
Regulation of blood coagulationC T Esmon
Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA
Biochim Biophys Acta 1477:349-60. 2000..Initial clinical studies suggest that supplementation with protein C may be useful in the treatment of acute inflammatory diseases such as sepsis...- The interactions between inflammation and coagulationCharles T Esmon
Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA
Br J Haematol 131:417-30. 2005..When the inflammation-coagulation interactions overwhelm the natural defence systems, catastrophic events occur, such as manifested in severe sepsis or inflammatory bowel disease... - Protein C pathway in sepsisCharles T Esmon
Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, 825 NE 13th Street, Oklahoma City, OK 73104, USA
Ann Med 34:598-605. 2002..This reduction may be due to both the anticoagulant effects as demonstrated by a reduction in D-dimer and inflammatory effects as demonstrated by a reduction in interleukin 6... - Is APC activation of endothelial cell PAR1 important in severe sepsis?: NoC T Esmon
OK Med Res Fndn and Howard Hughes Med Inst, Cardiovascular Biology, Oklahoma City, OK 73104, USA
J Thromb Haemost 3:1910-1. 2005 - Coagulation inhibitors in inflammationC T Esmon
Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Howard Hughes Medical Institute, Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
Biochem Soc Trans 33:401-5. 2005..This review examines the ways in which these pathways are down-regulated by inflammation, thus limiting clot formation and decreasing the natural anti-inflammatory mechanisms that these pathways possess... - Coagulation and inflammationCharles T Esmon
Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, 825 NE 13th Street, Oklahoma City, OK 73104, USA
J Endotoxin Res 9:192-8. 2003.... - Inflammation and thrombosisC T Esmon
Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104, USA
J Thromb Haemost 1:1343-8. 2003..This review will summarize the interactions between inflammation and coagulation... - The impact of the inflammatory response on coagulationCharles T Esmon
Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, OK, USA
Thromb Res 114:321-7. 2004..Inflammatory mediators like interleukin 6 can increase both platelet count and their responsiveness to agonists like thrombin. All of these events tend to shift the hemostatic balance in favor of clot formation... - The discovery of thrombomodulinC T Esmon
Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104, USA
J Thromb Haemost 2:209-13. 2004 - Crosstalk between inflammation and thrombosisCharles T Esmon
Department of Pathology, University of Oklahoma Health Sciences Center, Howard Hughes Medical Institute, 825 NE 13th Street, Oklahoma City, OK 73104, USA
Maturitas 47:305-14. 2004.... - Interactions between the innate immune and blood coagulation systemsCharles T Esmon
Oklahoma Medical Research Foundation, Dept of Pathology, University of Oklahoma Health Sciences Center, and Howard Hughes Medical Institute, Oklahoma City 73104, USA
Trends Immunol 25:536-42. 2004..This Review will summarize our current understanding of the mechanisms involved in the crosstalk between these two important systems... - Inflammation and the activated protein C anticoagulant pathwayCharles T Esmon
Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104, USA
Semin Thromb Hemost 32:49-60. 2006..Overall this pathway is critical to both regulation of the blood coagulation process, and control of the innate inflammatory response and some of its associated downstream pathologies... 
New mechanisms for vascular control of inflammation mediated by natural anticoagulant proteinsCharles T Esmon
Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Department of Pathology, University of Oklahoma Health Sciences Center, and Howard Hughes Medical Institute, Oklahoma City, OK 73104, USA
J Exp Med 196:561-4. 2002- The endothelial protein C receptorCharles T Esmon
Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma, USA
Curr Opin Hematol 13:382-5. 2006..This review covers the most recent evidence that relatively common genetic and acquired abnormalities of endothelial cell protein C receptor do contribute to pathophysiological disease processes... - The anticoagulant and anti-inflammatory roles of the protein C anticoagulant pathwayC T Esmon
Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Department of Pathology, University of Oklahoma Health Sciences Center and Howard Hughes Medical Institute, Oklahoma City, OK 73104, USA
J Autoimmun 15:113-6. 2000..The ability of the protein C system to modulate both inflammation and coagulation may explain i part why specific defects in the pathway appear to be associated with both arterial and venus thrombosis... - The protein C pathwayC Esmon
Oklahoma Medical Research Foundation, Oklahoma City 73104, USA
Crit Care Med 28:S44-8. 2000.... - Does inflammation contribute to thrombotic events?C T Esmon
Oklahoma Medical Research Foundation, Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, Okla, USA
Haemostasis 30:34-40. 2000..The requirement for multiple simultaneous injurious events probably explains why inflammation alone is not observed as a major cause of thrombosis... - The normal role of Activated Protein C in maintaining homeostasis and its relevance to critical illnessC T Esmon
Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Howard Hughes Medical Institute, Oklahoma City 73104, USA
Crit Care 5:S7-12. 2001..In vitro studies and animal models have shown that Activated Protein C blunts the inflammatory and coagulant response to sepsis through a variety of mechanisms... - Protein C anticoagulant pathway and its role in controlling microvascular thrombosis and inflammationC T Esmon
Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City 73104, USA
Crit Care Med 29:S48-51; discussion 51-2. 2001.... - Role of coagulation inhibitors in inflammationC T Esmon
Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City 73104, USA
Thromb Haemost 86:51-6. 2001..A phase III trial with tissue factor pathway inhibitor is in progress. In this review, the mechanisms by which the different natural anticoagulants are thought to function will be reviewed... - Crosstalk between inflammation and thrombosisCharles T Esmon
Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Department of Pathology, University of Oklahoma Health Sciences Center, Howard Hughes Medical Institute, Oklahoma City, OK 73104, USA
Maturitas 61:122-31. 2008.... - The protein C pathwayCharles T Esmon
Howard Hughes Medical Institute, Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA
Chest 124:26S-32S. 2003..APC has been shown clinically to protect patients with severe sepsis. Protein C and thrombomodulin are in early stage clinical trials for this disease, and each has distinct potential advantages and disadvantages relative to APC... - The crystal structure of the endothelial protein C receptor and a bound phospholipidVaheh Oganesyan
Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City 73104, USA
J Biol Chem 277:24851-4. 2002..The EPCR structure is a model for how CD1d binds lipids and further suggests additional potential functions for EPCR in immune regulation, possibly including the anti-phospholipid syndrome... - Effects of membrane and soluble EPCR on the hemostatic balance and endotoxemia in miceXunzhen Zheng
Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, The Howard Hughes Medical Institute, Oklahoma City 73104, USA
Blood 109:1003-9. 2007..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... - Inhibition of APC anticoagulant activity on oxidized phospholipid by anti-{beta}2-glycoprotein I monoclonal antibodiesOmid Safa
Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, 825 NE 13th St, Oklahoma City, OK 73104, USA
Blood 106:1629-35. 2005..We conclude that antibodies to beta(2)-GPI inhibit APC function specifically and contribute to a hypercoaguable state by disrupting specific protein-protein interactions induced by oxidation of PE-containing membranes... - Structure and functions of the endothelial cell protein C receptorCharles T Esmon
Department of Pathology, University of Oklahoma Health Sciences Center, Howard Hughes Medical Institute, Oklahoma City, OK, USA
Crit Care Med 32:S298-301. 2004..Thus, available data suggest a potential role of EPCR in hematopoiesis, autoimmunity, and the control of both the coagulation and inflammation responses to infection and trauma... - The APCs of neuroprotectionCharles T Esmon
Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, and Howard Hughes Medical Institute, Oklahoma City, Oklahoma 73104, USA
J Clin Invest 119:3205-7. 2009..Here we discuss the potential importance of these data and possible relevance to human neurodegenerative diseases... - Disruption of the endothelial cell protein C receptor gene in mice causes placental thrombosis and early embryonic lethalityJian Ming Gu
Cardiovascular Biology, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA
J Biol Chem 277:43335-43. 2002..We conclude that EPCR is essential for normal embryonic development. Moreover, EPCR plays a key role in preventing thrombosis at the maternal-embryonic interface... - Why do animal models (sometimes) fail to mimic human sepsis?Charles T Esmon
Departments of Pathology and Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
Crit Care Med 32:S219-22. 2004..To describe potential mechanisms that may account for the observation that drugs that work in treating sepsis in animal models often fail in sepsis trials in patients... - Basic mechanisms and pathogenesis of venous thrombosisCharles T Esmon
Oklahoma Medical Research Foundation, Howard Hughes Medical Institute, and Departments of Pathology and Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, United States
Blood Rev 23:225-9. 2009.... - Extracellular histones are major mediators of death in sepsisJun Xu
Oklahoma Medical Research Foundation, Oklahoma City, OK, USA
Nat Med 15:1318-21. 2009..We conclude that extracellular histones are potential molecular targets for therapeutics for sepsis and other inflammatory diseases... - Extraembryonic expression of EPCR is essential for embryonic viabilityWeihong Li
Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA
Blood 106:2716-22. 2005..Spontaneous thrombin formation in the deficient animals increases with age. These findings show that extraembryonic EPCR expression is critical for embryo development... - Distribution of endothelial cell protein C/activated protein C receptor (EPCR) during mouse embryo developmentJames T B Crawley
Oklahoma Medical Research Foundation, Howard Hughes Medical Institute, OK, USA
Thromb Haemost 88:259-66. 2002..However, not until postnatal day 7 did the intensity and distribution of EPCR staining mimic that observed in adult mice... - Inhibition of a thrombin anion-binding exosite-2 mutant by the glycosaminoglycan-dependent serpins protein C inhibitor and heparin cofactor IIScott T Cooper
Department of Pathology, The University of North Carolina at Chapel Hill, School of Medicine, Chapel Hill, NC 27599, USA
Thromb Res 107:67-73. 2002..In contrast, HCII does not require Arg(93), Arg(97) and Arg(101) of thrombin exosite-2 and further supports the hypothesis that HCII uses an allosteric process following glycosaminoglycan binding to inhibit thrombin... - Bench-to-bedside review: functional relationships between coagulation and the innate immune response and their respective roles in the pathogenesis of sepsisSteven M Opal
Infectious Disease Division, Brown University School of Medicine, Providence, Rhode Island, USA
Crit Care 7:23-38. 2003..The mechanisms by which these highly complex and coregulated defense strategies are linked together are the focus of the present review... - Thrombomodulin mutant mice with a strongly reduced capacity to generate activated protein C have an unaltered pulmonary immune response to respiratory pathogens and lipopolysaccharideAnita W Rijneveld
Academic Medical Center, University of Amsterdam, The Netherlands
Blood 103:1702-9. 2004..These data suggest that the capacity of TM to generate APC does not play a role of importance in the pulmonary response to respiratory pathogens or LPS... - Early loss of thrombomodulin expression impairs vein graft thromboresistance: implications for vein graft failureAntony Y Kim
Divisions of Cardiology, The Johns Hopkins School of Medicine, Baltimore, MD 21287, USA
Circ Res 90:205-12. 2002..Although enhanced local thrombin generation may predispose to early vein graft failure due to thrombosis, it does not seem to contribute significantly to late vein graft failure due to neointimal hyperplasia... - Role of the protein C pathway in the extraintestinal thrombosis associated with murine colitisHideo Yoshida
Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130 33932, USA
Gastroenterology 135:882-8. 2008..The objective of this study was to determine whether the protein C pathway contributes to the enhanced extraintestinal thrombosis that is associated with dextran sodium sulfate (DSS)-induced colitis in mice... - PAR1 cleavage and signaling in response to activated protein C and thrombinMatthew J Ludeman
Cardiovascular Research Institute, University of California, San Francisco, California 94143 0130, USA
J Biol Chem 280:13122-8. 2005..Although consistent with reports that sufficiently high concentrations of APC can cleave and activate PAR1 in culture, our data suggest that a significant physiological role for PAR1 activation by APC is unlikely... - Alternative mRNA is favored by the A3 haplotype of the EPCR gene PROCR and generates a novel soluble form of EPCR in plasmaBeatrice Saposnik
INSERM U765, Paris, France
Blood 111:3442-51. 2008..Trace amounts of the EPCR isoform were found in the plasma of A3 subjects. These results suggest that the sEPCRisoform could contribute to the regulatory effect of sEPCR in plasma... - Activated protein C protects against diabetic nephropathy by inhibiting endothelial and podocyte apoptosisBerend Isermann
Department of Medicine I and Clinical Chemistry, University of Heidelberg, INF 410, 69120 Heidelberg, Germany
Nat Med 13:1349-58. 2007..Conversely, maintaining high APC levels during long-term diabetes protects against diabetic nephropathy... - A comparative study of the protein C pathway in septic and nonseptic patients with organ failureDelphine Borgel
INSERM Unité 765, Paris, France
Am J Respir Crit Care Med 176:878-85. 2007..Severe sepsis is associated with an exacerbated procoagulant state with protein C (PC) system impairment. In contrast, the inflammatory and coagulation status of nonseptic patients with organ failure (OF) is less documented... - Endothelial cell protein C receptor acts as a cellular receptor for factor VIIa on endotheliumSamit Ghosh
Biomedical Research Division, The University of Texas Health Center at Tyler, Tyler, Texas 75708, USA
J Biol Chem 282:11849-57. 2007..Overall, the present data provide convincing evidence that EPCR serves as a cellular binding site for FVII/FVIIa. Further studies are needed to evaluate the pathophysiological consequences and relevance of FVIIa binding to EPCR... - Crystal structures of native and thrombin-complexed heparin cofactor II reveal a multistep allosteric mechanismTrevor P Baglin
Department of Haematology, Cambridge Institute for Medical Research, Wellcome Trust MRC Building, Hills Road, Cambridge CB2 2XY, United Kingdom
Proc Natl Acad Sci U S A 99:11079-84. 2002..Together, these structures reveal a multistep allosteric mechanism that relies on sequential contraction and expansion of the central beta-sheet of HCII... - Structure of the antithrombin-thrombin-heparin ternary complex reveals the antithrombotic mechanism of heparinWei Li
University of Cambridge, Department of Haematology, Division of Structural Medicine, Thrombosis Research Unit, Cambridge Institute for Medical Research, Wellcome Trust/MRC Building, Hills Road, Cambridge CB2 2XY, UK
Nat Struct Mol Biol 11:857-62. 2004..A notably close contact interface, comprised of extensive active site and exosite interactions, explains, in molecular detail, the basis of the antithrombotic properties of therapeutic heparin... - Shedding of endothelial protein C receptor contributes to vasculopathy and renal injury in lupus: in vivo and in vitro evidenceCarlos A Sesin
Department of Rheumatology, Hospital for Joint Diseases, New York University School of Medicine, New York, New York 10003, USA
Kidney Int 68:110-20. 2005..This study sought correlation between plasma levels of soluble EPCR and disease manifestation/severity, with a focus on lupus nephritis... - Venous thrombosis in the elderly: more questions than answersRoy L Silverstein
Department of Cell Biology, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA
Blood 110:3097-101. 2007 - Patients with severe sepsis vary markedly in their ability to generate activated protein CPatricia C Y Liaw
Department of Medicine, McMaster University, Hamilton, Ontario, Canada
Blood 104:3958-64. 2004..Baseline APC levels were higher in survivors (P = .024), and baseline F1 + 2/APC ratios were lower in survivors (P = .047). Larger studies are warranted to establish whether APC generation profiles aid in managing sepsis... - Localization of phosphatidylserine binding sites to structural domains of factor XaArvind Srivastava
Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, North Carolina 27599-7260, USA
J Biol Chem 277:1855-63. 2002.... - Endothelial protein C receptor (CD201) explicitly identifies hematopoietic stem cells in murine bone marrowAlejandro B Balazs
Department of Genetics, Harvard Medical School, Boston, MA 02115, USA
Blood 107:2317-21. 2006..Based on our findings, we believe EPCR represents the first known marker that 'explicitly' identifies hematopoietic stem cells within murine bone marrow... - The molecular basis of thrombin allostery revealed by a 1.8 A structure of the "slow" formJames A Huntington
Department of Haematology, University of Cambridge, Cambridge Institute for Medical Research, Wellcome Trust MRC Building, Hills Road, CB2 2XY, Cambridge, United Kingdom
Structure 11:469-79. 2003..These residues constitute an allosteric switch, which is flipped directly through sodium binding, resulting in the fast form with an open active site... - Molecular basis of thrombin recognition by protein C inhibitor revealed by the 1.6-A structure of the heparin-bridged complexWei Li
Department of Haematology, Division of Structural Medicine, Thrombosis Research Unit, Cambridge Institute for Medical Research, University of Cambridge, Wellcome Trust MRC Building, Hills Road, Cambridge CB2 0XY, United Kingdom
Proc Natl Acad Sci U S A 105:4661-6. 2008..These data significantly improve our understanding of the cofactor-dependent roles of PCI in hemostasis...