Thrombomodulin-Protein C-EPCR System

Efficacy and Safety of Recombinant Human Activated Protein C for Severe Sepsis

2001 • 5,900 citations

Protein C prevents the coagulopathic and lethal effects of Escherichia coli infusion in the baboon.

1987 • 836 citations

Activation of Endothelial Cell Protease Activated Receptor 1 by the Protein C Pathway

2002 • 832 citations

Isolation of a membrane-bound cofactor for thrombin-catalyzed activation of protein C.

1982 • 709 citations

Septic Shock, Multiple Organ Failure, and Disseminated Intravascular Coagulation

1992 • 708 citations

Purification and Characterization of TAFI, a Thrombin-activable Fibrinolysis Inhibitor

1995 • 684 citations

Gene Expression Profile of Antithrombotic Protein C Defines New Mechanisms Modulating Inflammation and Apoptosis

2001 • 655 citations

A new vitamin K-dependent protein. Purification from bovine plasma and preliminary characterization.

1976 • 634 citations

Activated protein C blocks p53-mediated apoptosis in ischemic human brain endothelium and is neuroprotective

2003 • 556 citations

The endothelial cell protein C receptor augments protein C activation by the thrombin-thrombomodulin complex.

1996 • 524 citations

Anticoagulant properties of bovine plasma protein C following activation by thrombin

1977 • 495 citations

Homozygous Protein C Deficiency Manifested by Massive Venous Thrombosis in the Newborn

1984 • 444 citations

Complex formation between thrombin and thrombomodulin inhibits both thrombin-catalyzed fibrin formation and factor V activation.

1982 • 434 citations

Inflammation and thrombosis

2003 • 411 citations

Lectin-like proteins in model organisms: implications for evolution of carbohydrate-binding activity

2001 • 374 citations

Tumor Necrosis Factor Suppresses Transcription of the Thrombomodulin Gene in Endothelial Cells

1988 • 367 citations

Structure and expression of human thrombomodulin, a thrombin receptor on endothelium acting as a cofactor for protein C activation.

1987 • 358 citations

Tumor necrosis factor leads to the internalization and degradation of thrombomodulin from the surface of bovine aortic endothelial cells in culture

1989 • 337 citations

The Lectin-like Domain of Thrombomodulin Confers Protection from Neutrophil-mediated Tissue Damage by Suppressing Adhesion Molecule Expression via Nuclear Factor κB and Mitogen-activated Protein Kinase Pathways

2002 • 331 citations

Functional properties of an endothelial cell cofactor for thrombin-catalyzed activation of protein C.

1981 • 330 citations

Time Course of Hemostatic Abnormalities in Sepsis and its Relation to Outcome

1993 • 310 citations

The endothelial cell protein C receptor aids in host defense against Escherichia coli sepsis

2000 • 298 citations

The profibrinolytic effect of activated protein C in clots formed from plasma is TAFI-dependent

1996 • 294 citations

Human Protein C Receptor Is Present Primarily on Endothelium of Large Blood Vessels

1997 • 288 citations

Tumor necrosis factor suppresses transcription of the thrombomodulin gene in endothelial cells.

1988 • 284 citations

Selective inhibitory effects of the anticoagulant activated protein C on the responses of human mononuclear phagocytes to LPS, IFN-gamma, or phorbol ester.

1994 • 277 citations

The thrombomodulin–protein C system is essential for the maintenance of pregnancy

2003 • 258 citations

Activated protein C attenuates endotoxin-induced pulmonary vascular injury by inhibiting activated leukocytes in rats

1996 • 252 citations

C-type lectins and galectins mediate innate and adaptive immune functions: their roles in the complement activation pathway

1999 • 238 citations

Absence of the blood-clotting regulator thrombomodulin causes embryonic lethality in mice before development of a functional cardiovascular system.

1995 • 235 citations

Human Protein C inhibits selectin-mediated cell adhesion: role of unique fucosylated oligosaccharide

1994 • 233 citations

Oxidation of a specific methionine in thrombomodulin by activated neutrophil products blocks cofactor activity. A potential rapid mechanism for modulation of coagulation.

1992 • 230 citations

Thrombin Activatable Fibrinolysis Inhibitor, a Potential Regulator of Vascular Inflammation

2003 • 222 citations

Soluble thrombomodulin as a predictor of incident coronary heart disease and symptomless carotid artery atheroscierosis in the Atherosclerosis Risk in Communities (ARIC) Study: a case-cohort study

1999 • 221 citations

Inactivation of C3a and C5a Octapeptides by Carboxypeptidase R and Carboxypeptidase N

2002 • 220 citations

Inhibition of staurosporine-induced apoptosis of endothelial cells by activated protein C requires protease-activated receptor-1 and endothelial cell protein C receptor

2003 • 217 citations

The Endothelial Cell Protein C Receptor

2000 • 213 citations

Thrombin‐induced chemotaxis and aggregation of neutrophils

1986 • 206 citations

The clinical spectrum of heterozygous protein C deficiency in a large New England kindred

1989 • 204 citations

The Crystal Structure of the Endothelial Protein C Receptor and a Bound Phospholipid

2002 • 197 citations

Activated protein C prevents LPS-induced pulmonary vascular injury by inhibiting cytokine production

1997 • 196 citations

Release of thrombomodulin from endothelial cells by concerted action of TNF-alpha and neutrophils: in vivo and in vitro studies.

1996 • 193 citations

Metalloproteolytic Release of Endothelial Cell Protein C Receptor

2000 • 184 citations

Thrombin and Phenotypic Modulation of the Endothelium

2003 • 184 citations

Endothelial expression of thrombomodulin is reversibly regulated by fluid shear stress.

1994 • 176 citations

Expression and function of the endothelial protein C receptor in human neutrophils

2003 • 176 citations

A haplotype of the EPCR gene is associated with increased plasma levels of sEPCR and is a candidate risk factor for thrombosis

2003 • 175 citations

Plasma Levels of Endothelial Cell Protein C Receptor Are Elevated in Patients With Sepsis and Systemic Lupus Erythematosus: Lack of Correlation With Thrombomodulin Suggests Involvement of Different Pathological Processes

1998 • 172 citations

Mechanisms by Which Soluble Endothelial Cell Protein C Receptor Modulates Protein C and Activated Protein C Function

2000 • 167 citations

Amino acid sequence of the light chain of bovine protein C.

1982 • 162 citations

Characterization of a cDNA for human protein C inhibitor. A new member of the plasma serine protease inhibitor superfamily.

1987 • 161 citations

Resistance to Activated Protein C and Factor V Leiden as Risk Factors for Venous Thrombosis

1995 • 161 citations

Identification of functional endothelial protein C receptor in human plasma.

1997 • 158 citations

Aggravation of endotoxin-induced disseminated intravascular coagulation and cytokine activation in heterozygous protein-C–deficient mice

2003 • 155 citations

The Last Three Consecutive Epidermal Growth Factor-like Structures of Human Thrombomodulin Comprise the Minimum Functional Domain for Protein C-activating Cofactor Activity and Anticoagulant Activity

1989 • 149 citations

Characterization of a Mouse Model for Thrombomodulin Deficiency

2001 • 145 citations

Diverse Substrate Recognition Mechanisms for Rhomboids: Thrombomodulin Is Cleaved by Mammalian Rhomboids

2004 • 142 citations

Functionally active protein C inhibitor/plasminogen activator inhibitor-3 (PCI/PAI-3) is secreted in seminal vesicles, occurs at high concentrations in human seminal plasma and complexes with prostate-specific antigen

1991 • 139 citations

Thrombomodulin-mediated Cell Adhesion

2003 • 137 citations

A new vitamin K-dependent protein. A phospholipid-binding zymogen of a serine esterase.

1976 • 134 citations

A 10-kDa cyanogen bromide fragment from the epidermal growth factor homology domain of rabbit thrombomodulin contains the primary thrombin binding site.

1988 • 130 citations

The Soluble Endothelial Protein C Receptor Binds to Activated Neutrophils: Involvement of Proteinase-3 and CD11b/CD18

2000 • 128 citations

Thrombomodulin expression by human blood monocytes and by human synovial tissue lining macrophages

1991 • 122 citations

Endotoxin and thrombin elevate rodent endothelial cell protein C receptor mRNA levels and increase receptor shedding in vivo

2000 • 122 citations

Statins increase thrombomodulin expression and function in human endothelial cells by a nitric oxide-dependent mechanism and counteract tumor necrosis factor alpha-induced thrombomodulin downregulation

2003 • 121 citations

Amino acid sequence of the heavy chain of bovine protein C.

1982 • 110 citations

A domain Composed of Epidermal Growth Factor-like Structures of Human Thrombomodulin Is Essential for Thrombin Binding and for Protein C Activation

1989 • 109 citations

Activation Mechanism of Anticoagulant Protein C in Large Blood Vessels Involving the Endothelial Cell Protein C Receptor

1998 • 108 citations

Functionally Active Thrombomodulin Is Present in Human Platelets1

1988 • 107 citations

Functional domains of membrane-bound human thrombomodulin. EGF-like domains four to six and the serine/threonine-rich domain are required for cofactor activity.

1992 • 105 citations

Structure and functions of the endothelial cell protein C receptor

2004 • 100 citations

Thrombomodulin: An overview and potential implications in vascular disorders

1998 • 98 citations

Coagulation and inflammation

2003 • 95 citations

The Endothelial Cell Protein C Receptor

1996 • 95 citations

Activation of Thrombin-activable Fibrinolysis Inhibitor Requires Epidermal Growth Factor-like Domain 3 of Thrombomodulin and Is Inhibited Competitively by Protein C

1998 • 95 citations

Elements of the Primary Structure of Thrombomodulin Required for Efficient Thrombin-activable Fibrinolysis Inhibitor Activation

2000 • 93 citations

Local Overexpression of Thrombomodulin for In Vivo Prevention of Arterial Thrombosis in a Rabbit Model

1999 • 92 citations

Thrombomodulin mutant mice with a strongly reduced capacity to generate activated protein C have an unaltered pulmonary immune response to respiratory pathogens and lipopolysaccharide

2003 • 89 citations

Thrombomodulin modulates growth of tumor cells independent of its anticoagulant activity.

1998 • 83 citations

Drotrecogin alfa (activated) (recombinant human activated protein C) for the treatment of severe sepsis

2003 • 83 citations

Activated protein C signals through the thrombin receptor PAR1 in endothelial cells

2003 • 79 citations

Regional distribution of thrombomodulin in human brain

1991 • 79 citations

Molecular Cloning and Expression of Murine and Bovine Endothelial Cell Protein C/Activated Protein C Receptor (EPCR)

1995 • 79 citations

Recombinant human activated protein C in sepsis: Inconsistent trial results, an unclear mechanism of action, and safety concerns resulted in labeling restrictions and the need for phase IV trials

2003 • 73 citations

Thrombomodulin expression by human keratinocytes. Induction of cofactor activity during epidermal differentiation.

1994 • 72 citations

Protein C Anticoagulant System in Patients with Interstitial Lung Disease

1998 • 71 citations

The discovery of thrombomodulin

2004 • 69 citations

Expression of Thrombomodulin in Atherosclerotic Lesions and Mitogenic Activity of Recombinant Thrombomodulin in Vascular Smooth Muscle Cells

1998 • 67 citations

Effects of human soluble thrombomodulin on experimental glomerulonephritis

2002 • 67 citations

Platelet factor 4 enhances generation of activated protein C in vitro and in vivo

2003 • 66 citations

Interaction Between Soluble Thrombomodulin and Intercellular Adhesion Molecule-1 in Predicting Risk of Coronary Heart Disease

2003 • 63 citations

Thrombin enhancement of interleukin-1 and tumor necrosis factor-alpha induced polymorphonuclear leukocyte migration.

1992 • 61 citations

Thrombomodulin-Dependent Anticoagulant Activity Is Regulated by Vascular Endothelial Growth Factor

1998 • 60 citations

Wall Tension Is a Potent Negative Regulator of In Vivo Thrombomodulin Expression

2003 • 58 citations

The Shape of Thrombomodulin and Interactions with Thrombin as Determined by Electron Microscopy

1996 • 54 citations

Transforming Growth Factor Betal and Beta2 Induce Down-Modulation of Thrombomodulin in Human Umbilical Vein Endothelial Cells

1995 • 52 citations

Acceleration of the thrombin inactivation of single chain urokinase-type plasminogen activator (pro-urokinase) by thrombomodulin.

1991 • 52 citations

Thrombomodulin gene regulation by cAMP and retinoic acid in F9 embryonal carcinoma cells.

1992 • 52 citations

Recombinant Human Soluble Thrombomodulin Reduces Endotoxin-Induced Pulmonary Vascular Injury Via Protein C Activation in Rats

1995 • 50 citations

The epidermal growth factor-like domain of recombinant human thrombomodulin exhibits mitogenic activity for Swiss 3T3 cells

1995 • 49 citations

Oxidized phospholipids in oxidized low-density lipoprotein down-regulate thrombomodulin transcription in vascular endothelial cells through a decrease in the binding of RARβ-RXRα heterodimers and Sp1 and Sp3 to their binding sequences in the TM promoter

2003 • 47 citations

Different glycoforms of human thrombomodulin

1991 • 46 citations

The Active Site of the Thrombin-Thrombomodulin Complex

1989 • 46 citations

Chemical carcinogens and antigens induce immune suppression via Langerhans' cell depletion

1996 • 45 citations

Antithrombotic effect of recombinant human soluble thrombomodulin on endotoxin-induced disseminated intravascular coagulation in rats

1993 • 44 citations

Activated protein C signals through the thrombin receptor PAR1 in endothelial cells

2003 • 39 citations

Coagulation and inflammation

2003 • 38 citations

Structure-Function Analyses of Thrombomodulin by Gene-Targeting in Mice: The Cytoplasmic Domain Is Not Required for Normal Fetal Development

1999 • 33 citations

Thrombomodulin Is a Cofactor for Thrombin Degradation of Recombinant Single-Chain Urokinase Plasminogen Activator "In Vitro" and in a Perfused Rabbit Heart Model

1992 • 33 citations

Modulation of Thrombomodulin-dependent Activation of Human Protein C through Differential Expression of Endothelial Smads

2002 • 32 citations

Differential effect of tumor necrosis factor-alpha on thrombomodulin gene expression by human monocytoid (THP-1) cell versus endothelial cells.

1998 • 32 citations

Soluble thrombomodulin and coronary heart disease

2003 • 30 citations

Intravenous extended infusion of recombinant human soluble thrombomodulin prevented tissue factor‐induced disseminated intravascular coagulation in rats

1994 • 29 citations

Thrombomodulin in the central nervous system.

1991 • 29 citations

Transcription of thrombomodulin mRNA in mouse hemangioma cells is increased by cycloheximide and thrombin.

1989 • 26 citations

Relation between dicrotic notch and mean pulmonary artery pressure studied by using a Swan-Ganz catheter in critically ill patients

1998 • 26 citations

Beyond sepsis: Activated protein C and ischemia–reperfusion injury

2004 • 22 citations

Baboon Model of Escherichia coli Sepsis: Description of its Four Stages and the Role of Tumor Necrosis Factor, Tissue Factors, and the Protein C System in Septic Shock1

2015 • 22 citations

Increased expression of thrombomodulin on the cultured human umbilical vein endothelial cells and mouse hemangioma cells by cyclic AMP

1991 • 21 citations

Thrombin-activatable fibrinolysis inhibitor TAFI deficient mice

2002 • 17 citations

Identification of the epidermal growth factor‐like domains of thrombomodulin essential for the acceleration of thrombin‐mediated inactivation of single‐chain urokinase‐type plasminogen activator

2001 • 16 citations

Molecular Model for the C-type Lectin Domain of Human Thrombomodulin

1998 • 14 citations

Upregulation of Thrombomodulin on Cultured Endothelial Cells by cAMP

1990 • 8 citations

Autoprothrombin II and autoprothrombin II anticoagulant.

1962 • 6 citations