thrombin

Summary

Summary: An enzyme formed from PROTHROMBIN that converts FIBRINOGEN to FIBRIN.

Top Publications

  1. ncbi Thrombin signalling and protease-activated receptors
    S R Coughlin
    Cardiovascular Research Institute and Department of Medicine, University of California at San Francisco, 94143 0130, USA
    Nature 407:258-64. 2000
  2. ncbi Thrombin induces epidermal growth factor receptor transactivation and CCL2 expression in human osteoblasts
    Chun Yin Huang
    China Medical University and China Medical University Hospital, Taichung, Taiwan
    Arthritis Rheum 64:3344-54. 2012
  3. ncbi Molecular cloning of a functional thrombin receptor reveals a novel proteolytic mechanism of receptor activation
    T K Vu
    Department of Medicine, University of California, San Francisco 94143 0524
    Cell 64:1057-68. 1991
  4. ncbi Dabigatran etexilate--a novel, reversible, oral direct thrombin inhibitor: interpretation of coagulation assays and reversal of anticoagulant activity
    Joanne van Ryn
    Department of Drug Discovery Support, Boehringer Ingelheim Pharma GmbH and Co KG, Biberach an der Riss, Germany
    Thromb Haemost 103:1116-27. 2010
  5. ncbi Calibrated automated thrombin generation measurement in clotting plasma
    H Coenraad Hemker
    Synapse BV, Cardiovascular Research Institute, University of Maastricht, Maastricht, The Netherlands
    Pathophysiol Haemost Thromb 33:4-15. 2003
  6. pmc Allosteric networks in thrombin distinguish procoagulant vs. anticoagulant activities
    Paul M Gasper
    Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla, CA 92093, USA
    Proc Natl Acad Sci U S A 109:21216-22. 2012
  7. pmc Extracellular histones promote thrombin generation through platelet-dependent mechanisms: involvement of platelet TLR2 and TLR4
    Fabrizio Semeraro
    Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA
    Blood 118:1952-61. 2011
  8. ncbi Clinical pharmacokinetics and pharmacodynamics of the oral direct thrombin inhibitor dabigatran etexilate
    Joachim Stangier
    Boehringer Ingelheim Pharma GmbH and Co KG, Biberach, Germany
    Clin Pharmacokinet 47:285-95. 2008
  9. ncbi A dual thrombin receptor system for platelet activation
    M L Kahn
    Cardiovascular Research Institute, Department of Medicine, University of California, San Francisco 94143 0130, USA
    Nature 394:690-4. 1998
  10. ncbi A critical review of the methods for cleavage of fusion proteins with thrombin and factor Xa
    Richard J Jenny
    Haematologic Technologies, Inc, Essex Junction, VT, USA
    Protein Expr Purif 31:1-11. 2003

Detail Information

Publications307 found, 100 shown here

  1. ncbi Thrombin signalling and protease-activated receptors
    S R Coughlin
    Cardiovascular Research Institute and Department of Medicine, University of California at San Francisco, 94143 0130, USA
    Nature 407:258-64. 2000
    How does the coagulation protease thrombin regulate cellular behaviour? The protease-activated receptors (PARs) provide one answer...
  2. ncbi Thrombin induces epidermal growth factor receptor transactivation and CCL2 expression in human osteoblasts
    Chun Yin Huang
    China Medical University and China Medical University Hospital, Taichung, Taiwan
    Arthritis Rheum 64:3344-54. 2012
    b>Thrombin is a key factor involved in the stimulation of fibrin deposition, angiogenesis, and proinflammatory processes. Abnormalities in these processes are primary features of rheumatoid arthritis (RA)...
  3. ncbi Molecular cloning of a functional thrombin receptor reveals a novel proteolytic mechanism of receptor activation
    T K Vu
    Department of Medicine, University of California, San Francisco 94143 0524
    Cell 64:1057-68. 1991
    We isolated a cDNA encoding a functional human thrombin receptor by direct expression cloning in Xenopus oocytes. mRNA encoding this receptor was detected in human platelets and vascular endothelial cells...
  4. ncbi Dabigatran etexilate--a novel, reversible, oral direct thrombin inhibitor: interpretation of coagulation assays and reversal of anticoagulant activity
    Joanne van Ryn
    Department of Drug Discovery Support, Boehringer Ingelheim Pharma GmbH and Co KG, Biberach an der Riss, Germany
    Thromb Haemost 103:1116-27. 2010
    Dabigatran etexilate is an oral, reversible direct thrombin inhibitor that is approved in the EU and several other countries for the prevention of venous thromboembolism after elective hip and knee replacement, and is in advanced clinical ..
  5. ncbi Calibrated automated thrombin generation measurement in clotting plasma
    H Coenraad Hemker
    Synapse BV, Cardiovascular Research Institute, University of Maastricht, Maastricht, The Netherlands
    Pathophysiol Haemost Thromb 33:4-15. 2003
    Calibrated automated thrombography displays the concentration of thrombin in clotting plasma with or without platelets (platelet-rich plasma/platelet-poor plasma, PRP/PPP) in up to 48 samples by monitoring the splitting of a fluorogenic ..
  6. pmc Allosteric networks in thrombin distinguish procoagulant vs. anticoagulant activities
    Paul M Gasper
    Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla, CA 92093, USA
    Proc Natl Acad Sci U S A 109:21216-22. 2012
    The serine protease α-thrombin is a dual-action protein that mediates the blood-clotting cascade...
  7. pmc Extracellular histones promote thrombin generation through platelet-dependent mechanisms: involvement of platelet TLR2 and TLR4
    Fabrizio Semeraro
    Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA
    Blood 118:1952-61. 2011
    ..Histones dose-dependently enhanced thrombin generation in PRP in the absence of any trigger, as evaluated by calibrated automated thrombinography regardless ..
  8. ncbi Clinical pharmacokinetics and pharmacodynamics of the oral direct thrombin inhibitor dabigatran etexilate
    Joachim Stangier
    Boehringer Ingelheim Pharma GmbH and Co KG, Biberach, Germany
    Clin Pharmacokinet 47:285-95. 2008
    The direct thrombin inhibitor dabigatran etexilate is currently in phase III of development for the prophylaxis and treatment of thromboembolic disorders, with three trials completed in primary venous thromboembolism (VTE) prevention...
  9. ncbi A dual thrombin receptor system for platelet activation
    M L Kahn
    Cardiovascular Research Institute, Department of Medicine, University of California, San Francisco 94143 0130, USA
    Nature 394:690-4. 1998
    Platelet-dependent arterial thrombosis triggers most heart attacks and strokes. Because the coagulation protease thrombin is the most potent activator of platelets, identification of the platelet receptors for thrombin is critical for ..
  10. ncbi A critical review of the methods for cleavage of fusion proteins with thrombin and factor Xa
    Richard J Jenny
    Haematologic Technologies, Inc, Essex Junction, VT, USA
    Protein Expr Purif 31:1-11. 2003
    ..b>Thrombin and factor Xa are the most frequently used proteases for this application...
  11. pmc Molecular cloning of a potential proteinase activated receptor
    S Nystedt
    Division of Molecular Neurobiology, Wallenberg Laboratory, Lund University, Sweden
    Proc Natl Acad Sci U S A 91:9208-12. 1994
    ..The predicted protein is similar in structure to the thrombin receptor and has a similar activation mechanism...
  12. ncbi Thrombin induces the release of angiopoietin-1 from platelets
    J J Li
    Department of Medicine, New York University Medical School, NY 10016, USA
    Thromb Haemost 85:204-6. 2001
    ..In this communication we report the incidence of Ang-1 in various normal tissues and demonstrate that thrombin-treated human platelets release angiopoietin-1 in vitro.
  13. ncbi Oral thrombin inhibitor dabigatran etexilate vs North American enoxaparin regimen for prevention of venous thromboembolism after knee arthroplasty surgery
    Jeffrey S Ginsberg
    McMaster University Medical Centre, Ontario, Canada
    J Arthroplasty 24:1-9. 2009
    Dabigatran, an oral once-daily unmonitored thrombin inhibitor, has been tested elsewhere using enoxaparin 40 mg once daily. We used the North American enoxaparin 30 mg BID regimen as the comparator...
  14. ncbi Thrombin stimulates human endothelial arginase enzymatic activity via RhoA/ROCK pathway: implications for atherosclerotic endothelial dysfunction
    Xiu Fen Ming
    Vascular Biology, Department of Medicine, Division of Physiology, University of Fribourg, Fribourg, Switzerland
    Circulation 110:3708-14. 2004
    ..This study investigated regulatory mechanisms of arginase activity in endothelial cells and its role in atherosclerosis...
  15. ncbi Thrombin-cleaved osteopontin regulates hemopoietic stem and progenitor cell functions through interactions with alpha9beta1 and alpha4beta1 integrins
    Jochen Grassinger
    Australian Stem Cell Centre, Clayton, Australia
    Blood 114:49-59. 2009
    ..The N-terminal thrombin cleavage fragment of OPN through its binding to the alpha(9)beta(1) and alpha(4)beta(1) integrins plays a key ..
  16. ncbi The metabolism and disposition of the oral direct thrombin inhibitor, dabigatran, in humans
    Stefan Blech
    Boehringer Ingelheim Pharma GmbH and Co KG, Department of Drug Metabolism and Pharmacokinetics, Biberach, Germany
    Drug Metab Dispos 36:386-99. 2008
    The pharmacokinetics and metabolism of the direct thrombin inhibitor dabigatran (BIBR 953 ZW, beta-alanine, N-[[2-[[[4-(aminoiminomethyl)phenyl]amino]methyl]-1-methyl-1H-benzimidazol-5-yl]carbonyl]-N-2-pyridinyl) were studied in 10 ..
  17. ncbi Novel oral factor Xa and thrombin inhibitors in the management of thromboembolism
    Bengt I Eriksson
    Department of Orthopaedics, Sahlgrenska University Hospital, Molndal, Sweden
    Annu Rev Med 62:41-57. 2011
    The last decade has seen the evaluation of several new oral anticoagulants that directly target thrombin or activated factor X (FXa)...
  18. ncbi Enhancement of incisional wound healing by thrombin conjugated iron oxide nanoparticles
    Ofra Ziv-Polat
    Department of Chemistry, Bar Ilan University, Ramat Gan, Israel
    Biomaterials 31:741-7. 2010
    b>Thrombin has been clinically used for topical hemostasis and wound management for more than six decades. The half-life of thrombin in human plasma is shorter than 15s due to close control by inhibitors...
  19. pmc PAR-1 and thrombin: the ties that bind the microenvironment to melanoma metastasis
    Maya Zigler
    Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
    Cancer Res 71:6561-6. 2011
    Progression of melanoma is dependent on cross-talk between tumor cells and the adjacent microenvironment. The thrombin receptor, protease-activated receptor-1 (PAR-1), plays a key role in exerting this function during melanoma progression...
  20. pmc Protease-activated receptors 1 and 4 mediate activation of human platelets by thrombin
    M L Kahn
    Cardiovascular Research Institute and Daiichi Research Center, University of California San Francisco, San Francisco, California 94143 0130, USA
    J Clin Invest 103:879-87. 1999
    Because of the role of thrombin and platelets in myocardial infarction and other pathological processes, identifying and blocking the receptors by which thrombin activates platelets has been an important goal...
  21. ncbi Guidance on the emergent reversal of oral thrombin and factor Xa inhibitors
    Scott Kaatz
    Department of Medicine, Henry Ford Hospital, Detroit, Michigan 48202, USA
    Am J Hematol 87:S141-5. 2012
    ..Also, the pros and cons of the possible use of four factor prothrombin complex concentrate are discussed...
  22. pmc RNA-seq reveals novel transcriptome of genes and their isoforms in human pulmonary microvascular endothelial cells treated with thrombin
    Li Qin Zhang
    Department of Pediatrics, Children s Mercy Hospitals and Clinics, University of Missouri School of Medicine, Kansas City, Missouri, United States of America
    PLoS ONE 7:e31229. 2012
    The dysregulation of vascular endothelial cells by thrombin has been implicated in the development of a number of pathologic disorders such as inflammatory conditions, cancer, diabetes, coronary heart disease...
  23. pmc Thrombin-aptamer recognition: a revealed ambiguity
    Irene Russo Krauss
    Universita di Napoli Federico II, Via Cintia, Napoli, Italia
    Nucleic Acids Res 39:7858-67. 2011
    ..The best-known example is the thrombin-binding aptamer, TBA, a single-stranded 15-mer DNA that inhibits the activity of thrombin, the key enzyme of ..
  24. ncbi Anticoagulants (thrombin inhibitors) and aspirin synergize with P2Y12 receptor antagonism in thrombosis
    Patrick Andre
    Millennium Pharmaceuticals, Inc, 256 E Grand Ave, South San Francisco, Calif 9408, USA
    Circulation 108:2697-703. 2003
    This study was designed to determine whether (1) P2Y12 antagonism synergizes with other antithrombotics and (2) anticoagulants (thrombin inhibitors) affect the antithrombotic activity elicited by P2Y12 antagonism.
  25. ncbi Cell-derived microparticles circulate in healthy humans and support low grade thrombin generation
    R J Berckmans
    Department of Clinical Chemistry, Leiden University Medical Center, The Netherlands
    Thromb Haemost 85:639-46. 2001
    We determined the numbers, cellular origin and thrombin-generating properties of microparticles in healthy individuals (n = 15)...
  26. ncbi Direct thrombin inhibitors
    Marcello Di Nisio
    Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands
    N Engl J Med 353:1028-40. 2005
  27. pmc Hyaluronic acid and thrombin upregulate MT1-MMP through PI3K and Rac-1 signaling and prime the homing-related responses of cord blood hematopoietic stem/progenitor cells
    Neeta Shirvaikar
    Canadian Blood Services R and D, Edmonton, Canada
    Stem Cells Dev 20:19-30. 2011
    ..We found that components of supernatants of leukapheresis products such as hyaluronic acid and thrombin (i) increase the secretion of proMMP-9 and transcription and protein synthesis of MT1-MMP in CB CD34(+) cells; (..
  28. ncbi Thrombin induces endothelial cell-surface exposure of the plasminogen receptor annexin 2
    Erica A Peterson
    Canadian Blood Services, R and D Department, 1800 Alta Vista Drive, Ottawa, ON K1G 4J5, Canada
    J Cell Sci 116:2399-408. 2003
    ..Because thrombin is a potent cell modulator obligately produced at the site of clot formation, we hypothesized that the amount of ..
  29. pmc Constitutive production and thrombin-induced release of vascular endothelial growth factor by human megakaryocytes and platelets
    R Mohle
    Developmental Hematopoiesis Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Proc Natl Acad Sci U S A 94:663-8. 1997
    ..In addition, immunohistochemistry showed intracytoplasmic VEGF in polyploid megakaryocytes. Thrombin stimulation of megakaryocytes and platelets resulted in rapid release of VEGF within 30 min...
  30. ncbi The structure of alpha-thrombin inhibited by a 15-mer single-stranded DNA aptamer
    K Padmanabhan
    Department of Chemistry, Michigan State University, East Lansing 48824 1322
    J Biol Chem 268:17651-4. 1993
    The structure of a complex between human alpha-thrombin and a GGTTGGTGTGGTTGG 15-nucleotide consensus sequence has been solved by x-ray crystallography and refined at 2.9-A resolution to an R value of 0.159...
  31. ncbi Enhanced thrombin generation in patients with cirrhosis-induced coagulopathy
    A Gatt
    The Haemophilia Centre and Thrombosis Unit, Royal Free Hospital, London, UK
    J Thromb Haemost 8:1994-2000. 2010
    ..b>Thrombin generation (TG) assays are global assays of coagulation that are showing promise in assessing bleeding and ..
  32. ncbi Thrombin induces increased expression and secretion of angiopoietin-2 from human umbilical vein endothelial cells
    Yao Qi Huang
    Department of Medicine and Kaplan Cancer Center, New York University Medical School, New York, NY 10016, USA
    Blood 99:1646-50. 2002
    Angiogenesis is required for tumor growth and metastasis. It has recently been suggested that thrombin is a potent promoter of angiogenesis...
  33. pmc Thrombin activity associated with neuronal damage during acute focal ischemia
    Bo Chen
    Department of Neurology, Cedars Sinai Medical Center, Los Angeles, CA 90048, USA
    J Neurosci 32:7622-31. 2012
    Mechanisms of ischemic neuronal and vascular injury remain obscure. Here we test the hypothesis that thrombin, a blood-borne coagulation factor, contributes to neurovascular injury during acute focal ischemia...
  34. ncbi Thrombin as a multi-functional enzyme. Focus on in vitro and in vivo effects
    Jolanta M Siller-Matula
    Department of Clinical Pharmacology, Medical University of Vienna, Wahringer Gurtel 18 20, A 1090 Vienna, Austria
    Thromb Haemost 106:1020-33. 2011
    b>Thrombin is the central protease in the coagulation cascade and one of the most extensively studied of all enzymes...
  35. ncbi Human AB serum and thrombin-activated platelet-rich plasma are suitable alternatives to fetal calf serum for the expansion of mesenchymal stem cells from adipose tissue
    Asli Kocaoemer
    Institute of Transfusion Medicine and Immunology, German Red Cross Blood Service of Baden Württemberg Hessen, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
    Stem Cells 25:1270-8. 2007
    ..To find a suitable FCS substitute, we investigated the effects of pooled human AB serum (AB-HS) and thrombin-activated platelet-rich plasma (tPRP) on adipose tissue MSCs (AT-MSCs) with FCS as the standard control medium...
  36. ncbi Pharmacology, pharmacokinetics, and pharmacodynamics of dabigatran etexilate, an oral direct thrombin inhibitor
    Joachim Stangier
    Department of Drug Metabolism and Pharmacokinetics, Boehringer Ingelheim Pharma GmbH and Co KG, Birkendorfer Strasse, Biberach an der Riss, Germany
    Clin Appl Thromb Hemost 15:9S-16S. 2009
    Dabigatran etexilate is a novel, oral reversible direct thrombin inhibitor that is rapidly absorbed and converted to its active form, dabigatran...
  37. ncbi PAR1 cleavage and signaling in response to activated protein C and thrombin
    Matthew J Ludeman
    Cardiovascular Research Institute, University of California, San Francisco, California 94143 0130, USA
    J Biol Chem 280:13122-8. 2005
    ..can trigger cellular responses via protease-activated receptor-1 (PAR1), a G protein-coupled receptor for thrombin. Whether this phenomenon contributes to the physiological effects of APC is unknown...
  38. ncbi Phosphorylation of threonine 558 in the carboxyl-terminal actin-binding domain of moesin by thrombin activation of human platelets
    F Nakamura
    Department of Pathology, Laboratory of Experimental Oncology, Stanford University School of Medicine, California 94305 5324, USA
    J Biol Chem 270:31377-85. 1995
    ..and localization of the membrane-linking protein moesin was analyzed during early activation of platelets with thrombin. Activated platelets elaborate filopodia and spread to assume flat pancake-like shapes, and moesin is localized ..
  39. ncbi Comparative pharmacodynamics and pharmacokinetics of oral direct thrombin and factor xa inhibitors in development
    Bengt I Eriksson
    Orthopaedics Department, University Hospital Sahlgrenska Ostra, Gothenburg, Sweden
    Clin Pharmacokinet 48:1-22. 2009
    ..The situation is changing with the development of orally active small molecules that directly target thrombin or activated factor X (FXa)...
  40. pmc Fucosylated chondroitin sulfate inhibits plasma thrombin generation via targeting of the factor IXa heparin-binding exosite
    Yang Buyue
    Department of Medicine Hematology Oncology, University of Wisconsin Madison, Madison, WI 53706, USA
    Blood 114:3092-100. 2009
    ..Heparin cofactor II (HCII)-dependent and -independent mechanisms for DHG inhibition of plasma thrombin generation were evaluated. When thrombin generation was initiated with 0...
  41. pmc Protease activated receptor 1 (PAR-1) activation by thrombin is protective in human pulmonary artery endothelial cells if endothelial protein C receptor is occupied by its natural ligand
    Jong Sup Bae
    Edward A Doisy Department of Biochemistry and Molecular Biology, St Louis University School of Medicine, 1100 S Grand Blvd, St Louis, MO 63104, USA
    Thromb Haemost 100:101-9. 2008
    ..protein C (APC)/protein C switches the protease activated receptor 1 (PAR-1)-dependent signaling specificity of thrombin from a disruptive to a protective effect in cultured human umbilical vein endothelial cells...
  42. pmc Thrombin stimulation of proteoglycan synthesis in vascular smooth muscle is mediated by protease-activated receptor-1 transactivation of the transforming growth factor beta type I receptor
    Micah L Burch
    From the Diabetes and Cell Biology Laboratory, BakerIDI Heart and Diabetes Institute, Melbourne, 3004 Victoria, Australia
    J Biol Chem 285:26798-805. 2010
    ..G-protein receptor-coupled agonists such as thrombin, signal changes the structure of proteoglycans produced by vascular smooth muscle cells (VSMCs)...
  43. ncbi Thrombin induces apoptotic events through the generation of reactive oxygen species in human platelets
    J J Lopez
    Department of Physiology Cellular Physiology Research Group, University of Extremadura, Caceres, Spain
    J Thromb Haemost 5:1283-91. 2007
    b>Thrombin is a major physiological platelet agonist that activates a number of cell functions including aggregation...
  44. ncbi Attenuation of thrombin-induced brain edema by cerebral thrombin preconditioning
    G Xi
    Department of Surgery Neurosurgery, University of Michigan, Ann Arbor, MI, USA
    Stroke 30:1247-55. 1999
    Edema formation after intracerebral hemorrhage has been linked to thrombin toxicity induced by the clot. However, thrombin at low concentrations actually protects neurons and astrocytes in culture from hypoglycemic and ischemic cell death...
  45. pmc The extended cleavage specificity of human thrombin
    Maike Gallwitz
    Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden
    PLoS ONE 7:e31756. 2012
    b>Thrombin is one of the most extensively studied of all proteases. Its central role in the coagulation cascade as well as several other areas has been thoroughly documented...
  46. ncbi Thrombin-induced endothelial microparticle generation: identification of a novel pathway involving ROCK-II activation by caspase-2
    Cédric Sapet
    INSERM U608 Physiopathologie de l Endothélium, 27 Boulevard Jean Moulin, 13385 Marseille Cedex 5, France
    Blood 108:1868-76. 2006
    b>Thrombin exerts pleiotropic effects on endothelial cells, including the release of microparticles (EMPs) that disseminate and exchange information with vascular cells...
  47. ncbi The axonally secreted serine proteinase inhibitor, neuroserpin, inhibits plasminogen activators and plasmin but not thrombin
    T Osterwalder
    Institute of Biochemistry, University of Zurich, Switzerland
    J Biol Chem 273:2312-21. 1998
    ..Although neuroserpin bound and inactivated plasminogen activators and plasmin, no interaction was observed with thrombin. A reactive site mutant of neuroserpin neither formed complexes with nor inhibited the amidolytic activity of any ..
  48. pmc Thrombomodulin is a determinant of metastasis through a mechanism linked to the thrombin binding domain but not the lectin-like domain
    Netanel A Horowitz
    Cancer and Blood Diseases Institute, Cincinnati Children s Hospital Medical Center, Cincinnati, OH 45229, USA
    Blood 118:2889-95. 2011
    ..endothelial transmembrane glycoprotein that modulates hemostatic function through a domain that controls thrombin-mediated proteolysis and an N-terminal lectin-like domain that controls inflammatory processes...
  49. pmc Thrombin induces NF-kappaB activation and IL-8/CXCL8 expression in lung epithelial cells by a Rac1-dependent PI3K/Akt pathway
    Chien Huang Lin
    Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
    J Biol Chem 286:10483-94. 2011
    We previously showed that thrombin induces interleukin (IL)-8/CXCL8 expression via the protein kinase C (PKC)α/c-Src-dependent IκB kinase α/β (IKKα/β)/NF-κB signaling pathway in human lung epithelial cells...
  50. ncbi Extracellular histones increase plasma thrombin generation by impairing thrombomodulin-dependent protein C activation
    C T Ammollo
    Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA
    J Thromb Haemost 9:1795-803. 2011
    ..The protein C-thrombomodulin (TM) system is a fundamental regulator of coagulation, particularly in the microvasculature, and its activity can be differentially influenced by interaction with several cationic proteins...
  51. ncbi Population pharmacokinetic analysis of the oral thrombin inhibitor dabigatran etexilate in patients with non-valvular atrial fibrillation from the RE-LY trial
    K H Liesenfeld
    Boehringer Ingelheim Pharma GmbH and Co KG, Biberach, Germany
    J Thromb Haemost 9:2168-75. 2011
    Dabigatran etexilate (DE) is an orally absorbed prodrug of dabigatran, a thrombin inhibitor that exerts potent anticoagulant and antithrombotic activity.
  52. pmc Anticoagulants and the propagation phase of thrombin generation
    Thomas Orfeo
    Department of Biochemistry, University of Vermont, Colchester, Vermont, United States of America
    PLoS ONE 6:e27852. 2011
    ..a search for new metrics, with significant focus directed at techniques that define the propagation phase of thrombin generation...
  53. ncbi Platelet microparticle membranes have 50- to 100-fold higher specific procoagulant activity than activated platelets
    Elena I Sinauridze
    National Research Center for Hematology, Russian Academy of Medical Sciences, 4a Novyi Zykovskii proezd, Moscow 125167, Russia
    Thromb Haemost 97:425-34. 2007
    ..Spatial clot growth rate (V(clot)) in the reaction-diffusion experimental model and endogenous thrombin potential (ETP) were determined in plasma, which was depleted of phospholipid cell surfaces by ultra-..
  54. ncbi The significance of circulating factor IXa in blood
    Saulius Butenas
    Department of Biochemistry, University of Vermont, Burlington, Vermont 05405 0068, USA
    J Biol Chem 279:22875-82. 2004
    ..study was to evaluate the influence of trace amounts of key coagulation proteases on tissue factor-independent thrombin generation using three models of coagulation...
  55. ncbi Activation of endothelial cell protease activated receptor 1 by the protein C pathway
    Matthias Riewald
    Department of Immunology, C204, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Science 296:1880-2. 2002
    ..Thus, the prototypical thrombin receptor is the target for EPCR-dependent APC signaling, suggesting a role for this receptor cascade in ..
  56. ncbi Rho and Rac but not Cdc42 regulate endothelial cell permeability
    B Wojciak-Stothard
    Ludwig Institute for Cancer Research, Royal Free and University College School of Medicine, London W1W 7BS, UK
    J Cell Sci 114:1343-55. 2001
    Endothelial permeability induced by thrombin and histamine is accompanied by actin stress fibre assembly and intercellular gap formation...
  57. ncbi Thrombin induces tumor growth, metastasis, and angiogenesis: Evidence for a thrombin-regulated dormant tumor phenotype
    Mary Lynn Nierodzik
    New York University School of Medicine, Department of Medicine Hematology, 550 First Avenue, New York, New York 10016, USA
    Cancer Cell 10:355-62. 2006
    ..However, it has not been fully appreciated that thrombin generated during thrombosis can augment the malignant phenotype...
  58. pmc Thrombin activates AMP-activated protein kinase in endothelial cells via a pathway involving Ca2+/calmodulin-dependent protein kinase kinase beta
    Nadine Stahmann
    Institute of Molecular Cell Biology, Friedrich Schiller University of Jena, Nonnenplan 2, 07743 Jena, Germany
    Mol Cell Biol 26:5933-45. 2006
    ..Our study of human endothelial cells shows that AMPK is activated by thrombin through a Ca2+-dependent mechanism involving the thrombin receptor protease-activated receptor 1 and Gq-protein-..
  59. ncbi The calibrated automated thrombogram (CAT): a universal routine test for hyper- and hypocoagulability
    H C Hemker
    Synapse BV, Cardiovascular Research Institute Maastricht, The Netherlands
    Pathophysiol Haemost Thromb 32:249-53. 2002
    By using a "slow" fluorogenic thrombin substrate and continuous comparison to a simultaneously run calibrator, thrombin generation can be monitored automatically, on line, in clotting PPP or PRP at a throughput of up to 100 samples per ..
  60. ncbi PKC-delta/c-Src-mediated EGF receptor transactivation regulates thrombin-induced COX-2 expression and PGE(2) production in rat vascular smooth muscle cells
    Hsi Lung Hsieh
    Department of Physiology and Pharmacology, Chang Gung University, Tao Yuan, Taiwan
    Biochim Biophys Acta 1783:1563-75. 2008
    The thrombin/proteinase-activated receptors (PARs) have been shown to regulate smooth muscle cell proliferation, migration, and vascular maturation...
  61. pmc Proteolysis of human thrombin generates novel host defense peptides
    Praveen Papareddy
    Division of Dermatology and Venereology, Department of Clinical Sciences, Lund University, Biomedical Center, Lund, Sweden
    PLoS Pathog 6:e1000857. 2010
    ..Here we show that C-terminal peptides of thrombin, a key enzyme in the coagulation cascade, constitute a novel class of host defense peptides, released upon ..
  62. ncbi Activated protein C mediates novel lung endothelial barrier enhancement: role of sphingosine 1-phosphate receptor transactivation
    James H Finigan
    Center for Translational Respiratory Medicine, Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland 21224, USA
    J Biol Chem 280:17286-93. 2005
    ..resistance (TER) and observed that APC produced concentration-dependent attenuation of TER reductions evoked by thrombin. We next explored known EC barrier-protective signaling pathways and observed dose-dependent APC-mediated ..
  63. pmc Activation of sphingosine kinase-1 reverses the increase in lung vascular permeability through sphingosine-1-phosphate receptor signaling in endothelial cells
    Mohammad Tauseef
    Department of Pharmacology and Center for Lung and Vascular Biology, College of Medicine, University of Illinois, Chicago, IL 60612, USA
    Circ Res 103:1164-72. 2008
    ..the increase in pulmonary microvessel permeability induced by challenge of mice with lipopolysaccharide or thrombin ligation of protease-activating receptor (PAR)-1...
  64. ncbi Pig thrombomodulin binds human thrombin but is a poor cofactor for activation of human protein C and TAFI
    J C Roussel
    Immunology Research Centre, St Vincent s Health, Fitzroy, Victoria, Australia
    Am J Transplant 8:1101-12. 2008
    Incompatibility between pig thrombomodulin (TM) and primate thrombin is thought to be an important factor in the development of microvascular thrombosis in rejecting pig-to-primate xenografts...
  65. pmc Dual regulation of glycogen synthase kinase 3 (GSK3)α/β by protein kinase C (PKC)α and Akt promotes thrombin-mediated integrin αIIbβ3 activation and granule secretion in platelets
    Samantha F Moore
    School of Physiology and Pharmacology, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, United Kingdom
    J Biol Chem 288:3918-28. 2013
    ..Here, we show that early thrombin-mediated GSK3 phosphorylation (0-30 s) was blocked by PKC inhibitors and largely absent in platelets from PKCα ..
  66. ncbi Is thrombin a key player in the 'coagulation-atherogenesis' maze?
    Julian Ilcheff Borissoff
    Laboratory for Clinical Thrombosis and Hemostasis, Department of Internal Medicine, Cardiovascular Research Institute Maastricht CARIM, Maastricht University Medical Center MUMC, Maastricht, The Netherlands
    Cardiovasc Res 82:392-403. 2009
    In addition to its established roles in the haemostatic system, thrombin is an intriguing coagulation protease demonstrating an array of effects on endothelial cells, vascular smooth muscle cells (VSMC), monocytes, and platelets, all of ..
  67. pmc Thrombin inhibition by argatroban ameliorates early brain injury and improves neurological outcomes after experimental subarachnoid hemorrhage in rats
    Takashi Sugawara
    Department of Physiology, Loma Linda University, Loma Linda, Calif 92354, USA
    Stroke 40:1530-2. 2009
    We investigated the role of thrombin in early brain injury after subarachnoid hemorrhage (SAH).
  68. ncbi Thrombin activates Ras-CREB/ATF-1 signaling and stimulates c-fos, c-jun, and c-myc expression in human gingival fibroblasts
    Chiu Po Chan
    Department of Dentistry, Chang Gung Memorial Hospital, Taipei, Taiwan
    J Periodontol 79:1248-54. 2008
    Protease-activated receptors (PARs) can be stimulated by thrombin and other proteases generated by periodontal pathogens...
  69. ncbi Neurosurgical complications of direct thrombin inhibitors--catastrophic hemorrhage after mild traumatic brain injury in a patient receiving dabigatran
    Sarah T Garber
    Department of Neurosurgery, University of Utah, Salt Lake City, Utah 84132, USA
    J Neurosurg 116:1093-6. 2012
    Dabigatran etexilate is an oral anticoagulant that acts as a direct, competitive thrombin inhibitor...
  70. ncbi Protease-activated receptor-1 signaling by activated protein C in cytokine-perturbed endothelial cells is distinct from thrombin signaling
    Matthias Riewald
    Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA
    J Biol Chem 280:19808-14. 2005
    ..We previously identified the prototypical thrombin receptor, protease-activated receptor-1 (PAR1), as part of a novel APC-endothelial cell protein C receptor (EPCR) ..
  71. pmc Thrombin promotes release of ATP from lung epithelial cells through coordinated activation of rho- and Ca2+-dependent signaling pathways
    Lucia Seminario-Vidal
    Department of Cell and Molecular Physiology, University of North Carolina, Chapel Hill, North Carolina 27599, USA
    J Biol Chem 284:20638-48. 2009
    ..The protease-activated receptor (PAR) agonist thrombin elicited a rapid Ca(2+)-dependent release of ATP from A549 cells...
  72. ncbi Thrombin and platelet activation
    Lawrence F Brass
    Departments of Medicine and Pharmacology, and the Center for Experimental Therapeutics, University of Pennsylvania, PA 19104, USA
    Chest 124:18S-25S. 2003
    The accumulation of thrombin at sites of vascular injury provides one of the chief means for recruiting platelets into a growing hemostatic plug...
  73. ncbi Evidence for actin cytoskeleton-dependent and -independent pathways for RelA/p65 nuclear translocation in endothelial cells
    Fabeha Fazal
    Department of Pediatrics, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA
    J Biol Chem 282:3940-50. 2007
    ..and -independent mechanisms of RelA/p65 nuclear transport using the proinflammatory mediators, thrombin and tumor necrosis factor alpha, respectively...
  74. pmc Thrombin flux and wall shear rate regulate fibrin fiber deposition state during polymerization under flow
    K B Neeves
    Department of Chemical Engineering, Colorado School of Mines, Golden, Colorado, USA
    Biophys J 98:1344-52. 2010
    b>Thrombin is released as a soluble enzyme from the surface of platelets and tissue-factor-bearing cells to trigger fibrin polymerization during thrombosis under flow conditions...
  75. pmc Substrate stiffening promotes endothelial monolayer disruption through enhanced physical forces
    Ramaswamy Krishnan
    Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, USA
    Am J Physiol Cell Physiol 300:C146-54. 2011
    ..On stiffer substrates, these forces were substantially enhanced by a hyperpermeability stimulus (thrombin, 1 U/ml), and gaps formed between cells...
  76. ncbi Thrombin potently enhances swelling-sensitive glutamate efflux from cultured astrocytes
    Gerardo Ramos-Mandujano
    Departamento de Biofisica, Instituto de Fisiologia Celular, Universidad Nacional Autonoma de Mexico, Mexico DF, Mexico
    Glia 55:917-25. 2007
    High concentrations of thrombin (Thr) have been linked to neuronal damage in cerebral ischemia and traumatic brain injury...
  77. pmc Thrombin generation, fibrin clot formation and hemostasis
    Alisa S Wolberg
    Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, 815 Brinkhous Bullitt Building, CB 7525, Chapel Hill, NC 27599 7525, USA
    Transfus Apher Sci 38:15-23. 2008
    Hemostatic clot formation entails thrombin-mediated cleavage of fibrinogen to fibrin. Previous in vitro studies have shown that the thrombin concentration present during clot formation dictates the ultimate fibrin structure...
  78. pmc The mammalian formin FHOD1 is activated through phosphorylation by ROCK and mediates thrombin-induced stress fibre formation in endothelial cells
    Ryu Takeya
    Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan
    EMBO J 27:618-28. 2008
    ..We also demonstrate that, in vascular endothelial cells, thrombin, a vasoactive substance leading to Rho activation, elicits both FHOD1 phosphorylation and stress fibre formation ..
  79. pmc Differential contributions of monocyte- and platelet-derived microparticles towards thrombin generation and fibrin formation and stability
    M M Aleman
    Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC 27599 7525, USA
    J Thromb Haemost 9:2251-61. 2011
    ..Microparticles (MPs) are sub-micron vesicles shed by activated or apoptotic cells, including platelets and monocytes. Increased circulating MPs are associated with thrombosis; however, their role in thrombogenesis is poorly understood...
  80. pmc New synthetic thrombin inhibitors: molecular design and experimental verification
    Elena I Sinauridze
    Laboratory of Physical Biochemistry, National Research Center for Hematology, Russian Academy of Medical Sciences, Moscow, Russia
    PLoS ONE 6:e19969. 2011
    ..The development of new anticoagulants is an important goal for the improvement of thromboses treatments...
  81. ncbi Reduced thrombin formation and altered fibrin clot properties induced by polyunsaturated omega-3 fatty acids on top of dual antiplatelet therapy in patients undergoing percutaneous coronary intervention (OMEGA-PCI clot)
    Grzegorz Gajos
    Department of Coronary Disease, Institute of Cardiology, Jagiellonian University Medical College, Krakow, Poland
    Arterioscler Thromb Vasc Biol 31:1696-702. 2011
    ..whether omega-3 polyunsaturated fatty acids (n-3 PUFA) are able to alter plasma fibrin clot properties and reduce thrombin formation in stable coronary artery disease patients undergoing percutaneous coronary intervention (PCI).
  82. ncbi Thrombomodulin domains attenuate atherosclerosis by inhibiting thrombin-induced endothelial cell activation
    Hsi Ju Wei
    Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan
    Cardiovasc Res 92:317-27. 2011
    b>Thrombin modulates the formation of atherosclerotic lesions by stimulating a variety of cellular effects through protease-activated receptor-1 (PAR-1) activation...
  83. ncbi Structure-based design of novel potent nonpeptide thrombin inhibitors
    Norbert H Hauel
    Boehringer Ingelheim Pharma KG, Research Division, Birkendorfer Strasse 65, D 88397 Biberach Riss, Germany
    J Med Chem 45:1757-66. 2002
    ..In this context, the serine protease thrombin plays a key role...
  84. ncbi Prediction of venous thromboembolism in patients with cancer by measuring thrombin generation: results from the Vienna Cancer and Thrombosis Study
    Cihan Ay
    Medical University of Vienna, Vienna, Austria
    J Clin Oncol 29:2099-103. 2011
    ..Laboratory tests measuring the overall thrombophilic tendency might be useful to assess VTE risk. The aim of this study was to investigate thrombin generation, a key process in hemostasis, as predictor of cancer-associated VTE.
  85. ncbi Thrombin-cleaved osteopontin levels in synovial fluid correlate with disease severity of knee osteoarthritis
    Masahiro Hasegawa
    Department of Orthopaedic Surgery, Mie University Graduate School of Medicine, 2 174 Edobashi, Tsu City, Mie 514 8507, Japan
    J Rheumatol 38:129-34. 2011
    ..Presence of the thrombin-cleaved form of OPN is well correlated with various inflammatory diseases...
  86. pmc Structure-activity studies and therapeutic potential of host defense peptides of human thrombin
    Gopinath Kasetty
    Division of Dermatology and Venereology, Department of Clinical Sciences, Lund University, Biomedical Center, Tornavagen 10, SE 22184 Lund, Sweden
    Antimicrob Agents Chemother 55:2880-90. 2011
    Peptides of the C-terminal region of human thrombin are released upon proteolysis and identified in human wounds...
  87. ncbi Early atherosclerosis exhibits an enhanced procoagulant state
    Julian Ilcheff Borissoff
    Laboratory for Clinical Thrombosis and Hemostasis, Department of Internal Medicine, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Universiteitsingel 50, PO Box 616, Box 8, 6200 MD Maastricht, The Netherlands
    Circulation 122:821-30. 2010
    b>Thrombin generation in vivo may be important in regulating atherosclerotic progression...
  88. ncbi Graphene fluorescence resonance energy transfer aptasensor for the thrombin detection
    Haixin Chang
    Department of Chemistry, Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology, Tsinghua University, Beijing 100084, People s Republic of China
    Anal Chem 82:2341-6. 2010
    ..In this work, a highly sensitive and specific fluorescence resonance energy transfer (FRET) aptasensor for thrombin detection is developed based on the dye labeled aptamer assembled graphene...
  89. ncbi Thrombin promotes actin stress fiber formation in RPE through Rho/ROCK-mediated MLC phosphorylation
    Ariadna Yolanda Ruiz-Loredo
    Division de Neurociencias, Instituto de Fisiologia Celular, Universidad Nacional Autonoma de Mexico, Mexico, D F, Mexico
    J Cell Physiol 226:414-23. 2011
    ..Most retinal diseases involve BRB breakdown, whereupon thrombin contained in serum directly contacts the RPE...
  90. ncbi Platelets and thrombin generation
    Dougald M Monroe
    Center for Thrombosis and Hemostasis, University of North Carolina, Chapel Hill 27599 7035, USA
    Arterioscler Thromb Vasc Biol 22:1381-9. 2002
    This review examines the evidence that platelets play a major role in localizing and controlling the burst of thrombin generation leading to fibrin clot formation...
  91. ncbi Role of Rho GTPases in thrombin-induced lung vascular endothelial cells barrier dysfunction
    Anna A Birukova
    Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA
    Microvasc Res 67:64-77. 2004
    b>Thrombin-induced barrier dysfunction of pulmonary endothelial monolayer is associated with dramatic cytoskeletal reorganization, activation of actomyosin contraction, and gap formation...
  92. pmc Impaired platelet responses to thrombin and collagen in AKT-1-deficient mice
    Juhua Chen
    Joseph J Jacobs Center for Thrombosis and Vascular Biology, Department of Molecular Cardiology, Joseph J Jacobs Center for Thrombosis and Vascular Biology, Cleveland Clinic Foundation, NB50, 9500 Euclid Ave, Cleveland, OH 44195, USA
    Blood 104:1703-10. 2004
    ..These differences were most apparent in platelets activated with low concentrations of thrombin. Although Akt-1 is not the predominant Akt isoform in mouse platelets, its absence diminished the amount of total ..
  93. ncbi Transient receptor potential canonical 3 (TRPC3) mediates thrombin-induced astrocyte activation and upregulates its own expression in cortical astrocytes
    Hisashi Shirakawa
    Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606 8501, Japan
    J Neurosci 30:13116-29. 2010
    ..b>Thrombin, a major blood-derived serine protease, leaks into the brain parenchyma upon blood-brain barrier disruption and ..
  94. ncbi Combinatorial synthesis of thrombin-binding aptamers containing iso-guanine
    Subba Rao Nallagatla
    Department of Chemistry, University of California, Riverside, California 92521, USA
    J Comb Chem 11:364-9. 2009
    A library of all possible substitutions of guanine by iso-guanine (iG) in the thrombin aptamer was prepared by split and mix synthesis. A colorimetric assay was used to screen for functional oligomers in the library...
  95. pmc Improved thrombin binding aptamer by incorporation of a single unlocked nucleic acid monomer
    Anna Pasternak
    Nucleic Acid Center, Department of Physics and Chemistry, University of Southern Denmark, 5230 Odense M, Denmark
    Nucleic Acids Res 39:1155-64. 2011
    ..aptamer (named TBA) adopts a G-quadruplex structure that strongly inhibits fibrin-clot formation by binding to thrombin. We have performed thermodynamic analysis, binding affinity and biological activity studies of TBA variants ..
  96. ncbi Thrombin up-regulates cathepsin D which enhances angiogenesis, growth, and metastasis
    Liang Hu
    Departments of Medicine and Radiation Oncology and Cell Biology, New York University School of Medicine, New York, New York
    Cancer Res 68:4666-73. 2008
    Cathepsin D (CD) up-regulation has been associated with human malignancy and poor prognosis. Thrombin up-regulated CD mRNA and protein in eight tumor cell lines as well as in human umbilical vascular endothelial cells (HUVEC)...
  97. pmc Heparin cofactor II-thrombin complex and dermatan sulphate:chondroitin sulphate ratio are biomarkers of short- and long-term treatment effects in mucopolysaccharide diseases
    Kia Jane Langford-Smith
    MPS Stem Cell Research Group, Faculty of Medical and Human Sciences, University of Manchester, Manchester, M13 9PT, UK
    J Inherit Metab Dis 34:499-508. 2011
    ..We evaluate heparin cofactor II-thrombin complex (HCII-T) as a biomarker in serum and dried blood spots (DBS) of MPS patients...
  98. pmc Thrombin induces tumor invasion through the induction and association of matrix metalloproteinase-9 and beta1-integrin on the cell surface
    A Reza Radjabi
    Department of Obstetrics and Gynecology Section of Gynecologic Oncology, Center for Integrative Science, University of Chicago, Chicago, IL 60637, USA
    J Biol Chem 283:2822-34. 2008
    The procoagulatory serine protease, thrombin, is known to induce invasion and metastasis in various cancers, but the mechanisms by which it promotes tumorigenesis are poorly understood...
  99. ncbi Thrombin induces nigral dopaminergic neurodegeneration in vivo by altering expression of death-related proteins
    Sang H Choi
    Brain Disease Research Center, Ajou University School of Medicine, Suwon 442 721, Korea
    Neurobiol Dis 14:181-93. 2003
    One week after intranigral injection of thrombin resulted in a dose-dependent loss of dopaminergic neurons (20-78%) in the rat substantia nigra (SN), as evidenced by tyrosine hydroxylase (TH) immunohistochemistry...
  100. ncbi Prothrombin/thrombin and the thrombin receptors PAR-1 and PAR-4 in the brain: localization, expression and participation in neurodegenerative diseases
    Elena Sokolova
    Otto von Guericke Universitaet Magdeburg, Medizinische Fakultat, Institut fur Neurobiochemie, Leipziger Strasse 44, Magdeburg, Germany
    Thromb Haemost 100:576-81. 2008
    Emerging evidence demonstrates that thrombin exerts physiological and pathological functions in the central nervous system. Both prothrombin and its active form thrombin have been detected locally in the brain...
  101. ncbi Identification of patients at low risk for recurrent venous thromboembolism by measuring thrombin generation
    Gregor Hron
    Department of Internal Medicine I, Medical University of Vienna, Austria
    JAMA 296:397-402. 2006
    ..Because of the large number of risk factors, assessing the risk of recurrence in an individual patient is complex. A method covering multicausal thrombophilia is therefore required...

Research Grants73

  1. Cross-talk Between Coagulation, Inflammation, and Immunity
    Lawrence L Leung; Fiscal Year: 2013
    ..Based on studies with the pCPB KO mice, we have obtained compelling data to support our general hypothesis that thrombin-activatable carboxypeptidase B (CPB or TAFIa) plays a broad anti-inflammatory role in vivo;the targets for CPB ..
  2. Clinical Development of Hemostatic Agent ClotFoam for Severe Hemorrhage
    Maja Nowakowski; Fiscal Year: 2013
    ..ClotFoam employs a new technology that bypasses the traditional mixture in situ of thrombin and fibrinogen, which translates in greater clotting efficacy and safety...
  3. Dual Direct Inhibitors of Thrombin and Factor Xa
    UMESH RAMANLAL DESAI; Fiscal Year: 2012
    ..3) Mechanistically, the new molecules inhibit thrombin, factor Xa and factor XIa with IC50 values in the range of 10-240 nM...
  4. MOLECULAR BIOLOGY OF HUMAN COAGULATION FACTOR V
    Thomas Ortel; Fiscal Year: 2010
    b>Thrombin generated by the prothrombinase complex contributes significantly to the pathogenesis of common clinical disorders such as myocardial infarction, deep vein thrombosis, pulmonary embolism, and stroke...
  5. Enhance Production of Functional Recombinant Human Protein C Variant In Mammalian
    Nienwen Chow; Fiscal Year: 2010
    ..3-carboxylation, to form a mature two-chain zymogen which circulates in plasma and can be converted to APC upon thrombin activation...
  6. The Role of Carboxypeptidase B and its Substrates in Rheumatoid Arthritis
    William H Robinson; Fiscal Year: 2013
    ..Recently, C3a, C5a, thrombin-cleaved osteopontin (OPN-R) and bradykinin were identified as additional substrates of CPB...
  7. STRUCTURE AND FUNCTION OF HEPARIN COFACTOR II
    Douglas M Tollefsen; Fiscal Year: 2010
    Heparin cofactor II (HCII) is an inhibitor of thrombin in plasma that can be activated by dermatan sulfate (DS) proteoglycans on vascular smooth muscle cells and fibroblasts...
  8. Thiol Isomerases During Thrombus Formation
    Barbara C Furie; Fiscal Year: 2013
    ..by calcium mobilization, platelet alpha granule release detected by P-selectin expression, fibrin formation, thrombin activity, platelet accumulation, platelet on/off rates, platelet thrombus embolization, microparticle ..
  9. The Role of Vascular Innervation on Tissue-type Plasminogen Activator Release
    JAMES ANTHONY SHEERIN MULDOWNEY; Fiscal Year: 2013
    ..Modification of these risk factors favorably alters vascular t-PA release. Our group has found that thrombin, but not bradykinin stimulates endothelial t-PA release in vitro...
  10. Dichotomous Roles of Thrombin in Acetaminophen Hepatotoxicity
    ROBERT ANDREW ROTH; Fiscal Year: 2013
    ..In human patients, coagulation cascade activation and thrombin generation accompanies the progression of APAP hepatotoxicity...
  11. Harness Germinal Matrix Hemorrhage
    John H Zhang; Fiscal Year: 2013
    ..A major causative factor of hydrocephalus formation is thrombin, a coagulation factor, activated by the intracranial bleed...
  12. GPCR Signaling &Vascular Wall Remodeling
    Gadiparthi N Rao; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Thrombin, a serine/threonine protease, besides its role in blood coagulation, plays a significant role as a mitogen and motogen to many cell types, in particular to vascular smooth muscle cells (VSMCs)..
  13. Tissue Factor &Clot Formation In Abdominal Aortic Aneurysm
    ALBERT PHILLIP OWENS; Fiscal Year: 2013
    ..Specifically, I will investigate te roles of tissue factor (TF), thrombin, platelets, and protease activated receptors (PARs) in the formation and progression of AAAs...
  14. TRANSGENIC ANALYSIS OF PLATELET RECEPTOR EXPRESSION
    Jerry Ware; Fiscal Year: 2012
    ..utility of these models resides in the fact that for several decades an interaction between platelet GP Ib-IX and thrombin has been described with little insight as to the physiologic relevance, if any, of the binding...
  15. Regulation of Endothelial ICAM-1 and PMN-Mediated Lung Injury by Actin Dynamics
    Fabeha Fazal; Fiscal Year: 2013
    ..provided by applicant): The overall objective of the proposed studies is to address the mechanisms by which thrombin, a serine protease released during clotting initiated by sepsis or vascular injury, regulates the expression of ..
  16. Platelet-Derived FVIII Gene Therapy of Hemophilia A
    Qizhen Shi; Fiscal Year: 2013
    ..The treated animals will be analyzed by the assays as described above, plus whole blood clotting time, thrombin generation assay and thromboelastography assay...
  17. P. papatasi midgut molecules: gene function and assessing TBV candidates
    JOSE MARCELO contact RAMALHO ORTIGAO; Fiscal Year: 2010
    ..Additionally, recently identified midgut transcripts such as those coding for peritrophins and thrombin-specific inhibitors will also be evaluated. Once identified, P...
  18. Screening for allosteric modulators of the protease activated receptor 4
    Heidi E Hamm; Fiscal Year: 2013
    ..Platelets play a critical role in thrombosis, the major cause of mortality and morbidity. Thrombin is present during neurotrauma and activates protease activated receptors, which causes oxidative stress and ..
  19. Rho- and GPCR-mediated signaling through novel cellular effectors
    Joan Heller Brown; Fiscal Year: 2012
    ..The extracellular stimuli (thrombin, LPA, S1P) and the intracellular pathway (activation of the small GTPase RhoA) that regulate these processes are ..
  20. Regulation of Rho Signaling by S-Nitrosothiols
    A Richard Whorton; Fiscal Year: 2012
    ..The Rho pathway is activated by vasoactive agonist including angiotensin II, endothelin I, thrombin, thromboxane A2, etc...
  21. Internalization of gap junctions as a regulatory mechanism of direct GJIC
    Matthias M Falk; Fiscal Year: 2013
    ..internalization of GJ plaques occurs naturally, for example in response to inflammatory mediators such as thrombin and endothelin...
  22. Role of Maternal Platelets in the Placenta and Pregnancy Complications
    Rashmi Sood; Fiscal Year: 2013
    ..We find that this model is driven by thrombin-mediated platelet activation and that pregnancy outcome is improved by heparin treatment, but not by treatment ..
  23. Randomized trial of inhaled nitric oxide to treat acute pulmonary embolism
    Jeffrey A Kline; Fiscal Year: 2013
    ..shear injury to the RV muscle, which releases proteins and nuclear material into the RV blood where it generates thrombin. Hemolysis also disrupts lung NO biosynthesis through the release of arginase-1, which depletes the endothelial ..
  24. Protective Role of the S1P-S1P1 Pathway in Pulmonary Fibrosis
    Andrew M Tager; Fiscal Year: 2013
    ..the hypothesis that increased activation of the coagulation cascade, and consequent increased activation of the thrombin receptor PAR-1, represents the mechanistic link between increased vascular leak produced by loss of S1P-S1P1 ..
  25. Coordinate Regulation Of Nuclear DGK-theta and PLD
    DANIEL RABEN; Fiscal Year: 2009
    ..two signaling enzymes, diacylglycerol kinase-theta and phospholipase D, at the nucleus in response to alpha-thrombin stimulation of fibroblasts. We have termed this regulation the "RhoA Switch"...
  26. Smooth Muscle Cell Tissue Factor and Cardiovascular Disease
    Mark B Taubman; Fiscal Year: 2013
    ..cardiovascular pathology, including direct effects on SMC physiology, indirect effects through the generation of thrombin, and as a source of procoagulant activity...
  27. 12-HETrE regulation of platelets
    MICHAEL ALLAN HOLINSTAT; Fiscal Year: 2013
    ..activity will be determined by identifying if it a) functions in a GPCR-dependent manner, b) can directly inhibit thrombin and collagen receptor signaling in the platelet, and c) mediates its actions in the platelet via inhibition of ..
  28. Physiology and Molecular Biology of Factor XI
    David Gailani; Fiscal Year: 2013
    ..provided by applicant): Factor XI (fXI) is the zymogen of a trypsin-like protease (fXIa) that contributes to thrombin generation by catalyzing factor IX (fIX) activation...
  29. Role of Fibrinolytic System in Vein Graft Remodeling
    William P Fay; Fiscal Year: 2013
    ..over-expression of PAI-1 on the activities of matrix metalloproteinase-2 (MMP-2), MMP-9, neutrophil elastase, and thrombin within vein grafts...
  30. Recombinant and Chemo-/Bio-Orthogonal Synthesis of Liposomal Thrombomodulin
    Xue Long Sun; Fiscal Year: 2013
    ..Endothelial thrombomodulin (TM) plays a critical role in local haemostasis by binding thrombin and subsequently converting protein C to its active form (APC), which is an anticoagulant protease that ..
  31. PROTEINS OF COAGULATION PATHWAYS
    John H Griffin; Fiscal Year: 2013
    ..plasma lipids and lipid-binding proteins that are newly discovered modulators of coagulation pathways and thrombin generation...
  32. Novel Molecules in Calcium Signaling in Platelets
    Wolfgang Bergmeier; Fiscal Year: 2013
    ..test our hypothesis that CD-GEFI-independent adhesion is relevant in vivo when thrombus formation is driven by thrombin under low shear conditions, such as in venous thrombosis models...
  33. Membrane Receptors Regulating Megakaryocyte Endocytosis of Factor V from Plasma
    BETH BOUCHARD; Fiscal Year: 2012
    Platelet- and plasma-derived factor Va serve an essential role in thrombin generation catalyzed by the prothrombinase complex, a 1:1, Ca2+-dependent complex of the cofactor factor Va and the serine protease factor Xa bound to activated ..
  34. The role of the terminal complement pathway in experimental cerebral malaria.
    Theresa N Ramos; Fiscal Year: 2012
    ..and progression? What is the relative importance of extrinsic protease activation pathway (via proteases such as thrombin and plasmin) to C5- mediated inflammation in ECM? Based on our preliminary observations, we hypothesize that C5 ..
  35. Microtubule-associated Rac
    Anna Birukova; Fiscal Year: 2013
    ..Our published studies show that edemagenic and pro-inflammatory agonists thrombin, TGF2 and TNF1 increase EC permeability via Rho-dependent alteration of MT dynamics leading to MT- dependent ..
  36. Therapeutic Protein C Activator for Myocardial Ischemia
    NORAH VERBOUT; Fiscal Year: 2013
    ..PCAs are recombinant thrombin analogs...
  37. Novel Anti-infective and Anti-thrombotic Micro-patterned Central Venous Catheter
    SHRAVANTHI REDDY; Fiscal Year: 2012
    ..Sharklet surfaces in a vascular environment, and 2) prove that we can decrease platelet adhesion and subsequent thrombin formation on Sharklet surfaces compared to un-patterned control surfaces...
  38. Thrombomodulin Receptors on Immune Cells
    John Morser; Fiscal Year: 2013
    ..Thrombomodulin (TM) is a cell surface glycoprotein that binds thrombin, the key effector enzyme of the coagulation cascade, converting it from a pro-coagulant and pro-inflammatory ..
  39. MOLECULAR BASIS OF BLOOD COAGULATION REGULATION
    Steven T Olson; Fiscal Year: 2013
    ..Two serpins, anti-thrombin and protein Z-dependent protease inhibitor (ZPI), are known to inhibit procoagulant proteases in a manner that is ..
  40. Mechanism of Staphylocoagulase-activated Blood Clotting
    Paul E Bock; Fiscal Year: 2013
    ..Aim 4 tests the idea that SfbX and ZAAP4 activate ProT by N- terminal insertion and will discover the substrates and adhesion proteins of the SfbX/ZAAP4.(pro)thrombin* complexes, providing insight into their roles in pathogenesis.
  41. Pathogen specific imaging of endocarditis
    PETER ROLF PANIZZI; Fiscal Year: 2013
    ..Staphylocoagulase's NH2-terminal D1 and D2-domains bind to thrombin (or the ProT imaging platform), while the COOH-terminal repeats region binds to fibrinogen at the same time...
  42. PROTEOLYSIS OF HMW FGF-2 BY THROMBIN AND ITS CARDIOVASCULAR IMPLICATIONS
    Giuseppe Pintucci; Fiscal Year: 2010
    ..We found that thrombin, a key protease of the coagulation cascade and inflammatory response, cleaves the high molecular weight (HMW) ..
  43. The role of lectin-complexes in complement-mediated coagulopathy
    Laura R La Bonte; Fiscal Year: 2011
    ..our knowledge, no studies have investigated the specific role and mechanisms of lectin-mediated coagulation and thrombin-like activity...
  44. Protein S: Neurovascular Protection in Stroke
    Berislav V Zlokovic; Fiscal Year: 2010
    ..its C-terminal sex hormone binding globulin-like (rSHBG) module, but not the N-terminal micro-PS [Gla domain, thrombin-sensitive (TSR) region, EGF1 module];(4) PS activates the PISK-Akt cell survival axis and inhibits the intrinsic ..
  45. Impaired integrin-dependent function of WASP-deficient platelets
    EILEEN REMOLD-O'DONNELL; Fiscal Year: 2010
    ..On activating platelets with thrombin plus stirring, these WASP molecules behaved like genuine membrane skeletal proteins, undergoing activation by ..
  46. Novel Therapeutic Approach for Sepsis: Blocking the Vascular Response to Cytokine
    ALAN L MUELLER; Fiscal Year: 2012
    ..with the downstream signaling cascades from multiple permeability factors including TNF-alpha, interleukins, and thrombin. We have cloned an active fragment of Slit2, Slit2N, which appears to have identical efficacy to Slit2, and is ..
  47. Thrombin Mediated Cytotoxicity during Cerebral Ischemia
    Patrick D Lyden; Fiscal Year: 2013
    ..b>Thrombin is a serine protease that plays a critical role in the coagulation cascade...
  48. Hemostatic-antibiotic Combination for Prevention of MRSA Surgical Site Infections
    Timothy C Fisher; Fiscal Year: 2010
    ..g., thrombin, collagen, fibrin)...
  49. Association of TFPI with antemortem dementia and postmortem micro brain infarcts
    SUSAN ANTONE MARONEY; Fiscal Year: 2013
    ..blood vessel has been damaged, and FXa, a major component of the clotting system that produces a large amount of thrombin resulting in clot formation. TFPI is found in endothelial cells, in platelets or in plasma...
  50. Mechanisms linking the hemostatic protease thrombin to arthritic disease
    Matthew J Flick; Fiscal Year: 2013
    ..Activation of the hemostatic system and the subsequent conversion of prothrombin to the active serine protease thrombin is a prominent feature of RA...
  51. Targeting myofibroblast activation in chronic fibrotic disease
    ARTHUR ROGER STRAUCH; Fiscal Year: 2011
    ..type I collagen promoters and clarify how these proteins are affected by pro-fibrotic agents such as TGFbeta1 and thrombin that, if unchecked, may cause myofibroblast progression to hypertrophic scarring...
  52. Glial-Neural Interactions in Autonomic Control
    Richard C Rogers; Fiscal Year: 2012
    ..The discovery of "thrombin receptor" [proteinase activated receptor - PAR] in the brainstem led us to the hypothesis that proteinase action ..
  53. Serpin Regulation of Coagulation Proteases
    Alireza R Rezaie; Fiscal Year: 2013
    ..Anti-thrombin (AT) is a major serpin that regulates the proteolytic activity of coagulation proteases of both intrinsic and ..
  54. Model of Platelet Adhesion and Thrombus Formation
    Michael R King; Fiscal Year: 2013
    ..receptor: ligand interactions required for platelet activation such as GPVI: collagen, P2Y12:ADP, and PAR1:thrombin. This will enable us to apply our model to predicting possible deleterious consequences associated with the ..
  55. Sex Differences in Vascular Markers of Stroke Risk
    Cheryl D Bushnell; Fiscal Year: 2012
    ..The reason may be related to unrecognized subclinical disease, which may be manifested by ongoing thrombin generation, inflammation, endothelial dysfunction, and abnormal responses to vascular stresses...
  56. TRPV4 Initiates Ventilator Induced Lung Injury
    James C Parker; Fiscal Year: 2010
    ..Data) that lung epithelial cell monolayers co-cultured with alveolar macrophages activated with trypsin (PAR2), thrombin (PAR1, 3, 4) or the TRPV4 agonist, 4alpha-phoroot 12,13--didecanoate (4a-PDD) given separately actually decreased ..
  57. The Role of Ets-1 in Vascular Inflammation
    J PETER PETER OETTGEN; Fiscal Year: 2011
    ..Ets-1 is upregulated in response to PDGF-BB, Angiotensin II, and thrombin. Chronic infusion of AngII in mice promotes vascular remodeling that begins with the recruitment of inflammatory ..
  58. Protease Activated Receptor Signaling by Coagulation Proteases
    Alireza R Rezaie; Fiscal Year: 2013
    ..C receptor (EPCR) elicits a barrier protective response via activation of PAR-1 in vascular endothelial cells, thrombin elicits a barrier disruptive response via the activation of the same receptor...
  59. 2012 New Insights into Coagulation
    Eleanor Pollak; Fiscal Year: 2012
    ..well-established coagulation agents: heparin and low-molecular weight heparin, warfarin, and intravenous direct thrombin inhibitors...
  60. Effect of Statins and Modifiable Factors on Stroke Outcome in Atrial Fibrillation
    Elaine Hylek; Fiscal Year: 2012
    ..like hyperglycemia, infection, accelerated hypertension, heart failure, and dyslipidemia are potent triggers for thrombin generation, their effect on AF stroke outcomes has not been studied...
  61. Mechanisms of Venous Thromboembolism in Cancer
    Nigel Mackman; Fiscal Year: 2012
    ..also measure whole blood TF activity, cellular origin of the TF-positive MPs and coagulation activation markers (thrombin anti thrombin complexes and D- dimer)...
  62. Insights on Selected Procoagulation Markers and Outcomes in Stroke Trial (I-SPOT)
    ANGARA KONETI RAO; Fiscal Year: 2013
    ..tissue factor procoagulant activity (TF-PCA) and plasma activated factor VII (FVIIa) and markers of thrombin generation, prothrombin fragment 1.2 (F1...
  63. ANTIBODIES WITH PROTHROMBINASE ACTIVITY IN LUPUS
    Perumal Thiagarajan; Fiscal Year: 2003
    Prothrombin is the precursor of thrombin, the central enzyme in blood coagulation...
  64. Structure/Function Study of the Anticoagulant Protein S
    Alan Rigby; Fiscal Year: 2005
    ..The penultimate step in blood coagulation is the conversion of prothrombin to thrombin, which is then responsible for the conversion of fibrinogen to fibrin...
  65. Structural Mechanisms for the Inhibition of Thrombosis
    JAMES HUNTINGTON; Fiscal Year: 2009
    ..The long-term goal of this research is to understand the three natural mechanisms which control the activity of thrombin, the final protease of the blood coagulation cascade: 1) prevention of thrombin formation through inhibition of ..
  66. Mechanisms of Hemostatic Protease Inhibition by Serpins
    Ingrid M Verhamme; Fiscal Year: 2010
    The long-term goal is to define the molecular mechanisms of thrombin (T) inhibition by the serpins, heparin cofactor II (HCII) and plasminogen activator inhibitor-1 (PAI-1), implicated in arterial thrombosis...
  67. PROTEIN PHOSPHATASES IN ENDOTHELIAL CELL PERMEABILITY
    JOE GARCIA; Fiscal Year: 2001
    ..Contractile proteins, actin and myosin, control permeability and bioactive agonists such as thrombin induce endothelial cell contraction, intercellular gap formation and barrier dysfunction by signaling changes in ..
  68. THROMBIN AND VWF IN SHIGA-TOXIN-ASSOCIATED HUS
    Thomas Raife; Fiscal Year: 2001
    ..Many investigations have implicated either von Willebrand factor (vWF)-platelet interactions, or thrombin-mediated coagulation pathways as primary pathological mechanisms...
  69. Physiological Role of Fibrin Anti-Thrombin I Activities
    MICHAEL MOSESSON; Fiscal Year: 2005
    b>Thrombin binding to fibrinogen at its substrate recognition sites in the central E domain leads to proteolytic conversion of fibrinogen to fibrin...
  70. MOLECULAR MECHANISM OF THROMBIN INHIBITION
    Scott Cooper; Fiscal Year: 2003
    ..the different mechanisms by which the serpins antithrombin (AT) and protein C inhibitor (PCI) inhibit free thrombin and thrombin bound to thrombomodulin (TM)...
  71. Endothelial Dysfunction in Intestinal Radiation Toxicity
    Martin Hauer Jensen; Fiscal Year: 2009
    ..TM is an endothelial cell protein that modulates thrombin's functions, and essentially converts thrombin from a pro-coagulant to an anticoagulant...
  72. Thrombin signaling in Hemostatis and thrombosis
    Shaun R Coughlin; Fiscal Year: 2010
    A central goal of my laboratory has been to determine how thrombin regulates cellular behaviors involved in hemostasis, thrombosis, inflammation and other processes, and to elucidate the roles of thrombin signaling in vivo...
  73. G Proteins and Endothelial Barrier Regulation
    Tatyana Voyno Yasenetskaya; Fiscal Year: 2004
    ..In endothelial cells, thrombin activates G protein-coupled receptors and induces actin stress fibers followed by intercellular gap formation, ..