plasminogen activators

Summary

Summary: A heterogeneous group of proteolytic enzymes that convert PLASMINOGEN to PLASMIN. They are concentrated in the lysosomes of most cells and in the vascular endothelium, particularly in the vessels of the microcirculation.

Top Publications

  1. ncbi Detection of plasminogen activators in oral cancer by laser capture microdissection combined with zymography
    Alejandro Curino
    Proteases and Tissue Remodeling Unit, Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, 30 Convent Drive, Bethesda, MD 20892, USA
    Oral Oncol 40:1026-32. 2004
  2. ncbi Plasminogen activators in multiple sclerosis lesions: implications for the inflammatory response and axonal damage
    D Gveric
    Department of Neurochemistry, Institute of Neurology, University College London, UK
    Brain 124:1978-88. 2001
  3. 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
  4. ncbi A proposed reference method for plasminogen activators that enables calculation of enzyme activities in SI units
    C Longstaff
    Division of Haematology, National Institute for Biological Standards and Control, Potters Bar, Hertfordshire, UK
    J Thromb Haemost 2:1416-21. 2004
  5. pmc Myosin light chain kinase functions downstream of Ras/ERK to promote migration of urokinase-type plasminogen activator-stimulated cells in an integrin-selective manner
    D H Nguyen
    Department of Biochemistry and Molecular Genetics, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908, USA
    J Cell Biol 146:149-64. 1999
  6. ncbi Extracellular proteolysis in brain injury and inflammation: role for plasminogen activators and matrix metalloproteinases
    Eng H Lo
    Neuroprotection Research Laboratory, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
    J Neurosci Res 69:1-9. 2002
  7. ncbi Accelerating thrombolysis with chitosan-coated plasminogen activators encapsulated in poly-(lactide-co-glycolide) (PLGA) nanoparticles
    Tze Wen Chung
    Department of Chemical Engineering, National Yunlin University of Science and Technology, Tou Liu, Yunlin, Taiwan, ROC
    Biomaterials 29:228-37. 2008
  8. ncbi A urokinase receptor-associated protein with specific collagen binding properties
    N Behrendt
    Finsen Laboratory, Rigshospitalet, DK 2100 Copenhagen O, Denmark
    J Biol Chem 275:1993-2002. 2000
  9. pmc Structural basis for activation of an integral membrane protease by lipopolysaccharide
    Elif Eren
    Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
    J Biol Chem 287:23971-6. 2012
  10. ncbi Purification, cloning, and characterization of a profibrinolytic plasminogen-binding protein, TIP49a
    S B Hawley
    Department of Vascular Biology CVN 26, Scripps Research Institute, La Jolla, California 92037, USA
    J Biol Chem 276:179-86. 2001

Detail Information

Publications281 found, 100 shown here

  1. ncbi Detection of plasminogen activators in oral cancer by laser capture microdissection combined with zymography
    Alejandro Curino
    Proteases and Tissue Remodeling Unit, Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, 30 Convent Drive, Bethesda, MD 20892, USA
    Oral Oncol 40:1026-32. 2004
    ..In conclusion, LCM combined with zymography may be excellently suited for analyzing the prognostic significance and causal involvement of the plasminogen activation system in oral cancer...
  2. ncbi Plasminogen activators in multiple sclerosis lesions: implications for the inflammatory response and axonal damage
    D Gveric
    Department of Neurochemistry, Institute of Neurology, University College London, UK
    Brain 124:1978-88. 2001
    ..tPA localization on injured axons may be a marker of axonal damage or represent a protective mechanism aimed at removal of fibrin deposits and restoration of axonal function...
  3. 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...
  4. ncbi A proposed reference method for plasminogen activators that enables calculation of enzyme activities in SI units
    C Longstaff
    Division of Haematology, National Institute for Biological Standards and Control, Potters Bar, Hertfordshire, UK
    J Thromb Haemost 2:1416-21. 2004
    A method has been developed for accurately and precisely measuring the activity of a range of plasminogen activators (PAs) used as thrombolytic agents, including streptokinase, tissue plasminogen activator (tPA) and variants, and ..
  5. pmc Myosin light chain kinase functions downstream of Ras/ERK to promote migration of urokinase-type plasminogen activator-stimulated cells in an integrin-selective manner
    D H Nguyen
    Department of Biochemistry and Molecular Genetics, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908, USA
    J Cell Biol 146:149-64. 1999
    ..Thus, we have demonstrated that uPA promotes cellular migration, in an integrin-selective manner, by initiating a uPAR-dependent signaling cascade in which Ras, MEK, ERK, and MLCK serve as essential downstream effectors...
  6. ncbi Extracellular proteolysis in brain injury and inflammation: role for plasminogen activators and matrix metalloproteinases
    Eng H Lo
    Neuroprotection Research Laboratory, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
    J Neurosci Res 69:1-9. 2002
    ..As the mechanisms of deleterious vs. potentially beneficial PA and MMP actions become better defined, it is hoped that new therapeutic targets will emerge for ameliorating the sequelae of brain injury and inflammation...
  7. ncbi Accelerating thrombolysis with chitosan-coated plasminogen activators encapsulated in poly-(lactide-co-glycolide) (PLGA) nanoparticles
    Tze Wen Chung
    Department of Chemical Engineering, National Yunlin University of Science and Technology, Tou Liu, Yunlin, Taiwan, ROC
    Biomaterials 29:228-37. 2008
    Accelerating thrombolysis using plasminogen activators (PAs) encapsulated liposomes or PEG microparticles by pressure-driven permeation have been demonstrated in vitro and in vivo in animal models...
  8. ncbi A urokinase receptor-associated protein with specific collagen binding properties
    N Behrendt
    Finsen Laboratory, Rigshospitalet, DK 2100 Copenhagen O, Denmark
    J Biol Chem 275:1993-2002. 2000
    ..This collagen binding reaction at the exact site of plasminogen activation on the cell may lead to adhesive functions as well as a contribution to cellular degradation of collagen matrices...
  9. pmc Structural basis for activation of an integral membrane protease by lipopolysaccharide
    Elif Eren
    Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
    J Biol Chem 287:23971-6. 2012
    ....
  10. ncbi Purification, cloning, and characterization of a profibrinolytic plasminogen-binding protein, TIP49a
    S B Hawley
    Department of Vascular Biology CVN 26, Scripps Research Institute, La Jolla, California 92037, USA
    J Biol Chem 276:179-86. 2001
    ..These results suggest that TIP49a is a previously unrecognized plasminogen-binding protein on the U937 cell surface...
  11. ncbi Plasminogen activation and cancer
    Keld Danø
    Finsen Laboratory, Rigshospitalet, Strandboulevarden 49, DK 2100 Copenhagen, Denmark
    Thromb Haemost 93:676-81. 2005
    ..Therefore for each type of cancer, a combination of protease inhibitors that is optimised with respect to both maximal therapeutic effect and minimal toxic side effects need to be identified...
  12. ncbi The plasminogen activation system in tumor growth, invasion, and metastasis
    P A Andreasen
    Department of Molecular and Structural Biology, Aarhus University, Denmark
    Cell Mol Life Sci 57:25-40. 2000
    ..plasminogen can be catalyzed by either of two other serine proteinases, the urokinase- and tissue-type plasminogen activators (uPA and tPA)...
  13. ncbi The plasminogen activator system: biology and regulation
    J P Irigoyen
    Friedrich Miescher Institute, Basel, Switzerland
    Cell Mol Life Sci 56:104-32. 1999
    The regulation of plasminogen activation involves genes for two plasminogen activators (tissue type and urokinase type), two specific inhibitors (type 1 and type 2), and a membrane-anchored urokinase-type plasminogen-activator-specific ..
  14. ncbi An active site water network in the plasminogen activator pla from Yersinia pestis
    Elif Eren
    Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA
    Structure 18:809-18. 2010
    ..The Pla structure suggests a model for the interaction with plasminogen substrate and provides a more detailed understanding of the catalytic mechanism of omptin proteases...
  15. ncbi Identification of a urokinase receptor-integrin interaction site. Promiscuous regulator of integrin function
    D I Simon
    Cardiovascular, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 275:10228-34. 2000
    ....
  16. pmc Plasminogen enhances neuritogenesis on laminin-1
    Ana Gutierrez-Fernandez
    Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
    J Neurosci 29:12393-400. 2009
    ..This study provides the first direct evidence that plasminogen participates in neurite outgrowth and also suggests that laminin-1 degradation by plasmin contributes to the process of neuritogenesis...
  17. ncbi Cell-surface actin binds plasminogen and modulates neurotransmitter release from catecholaminergic cells
    Lindsey A Miles
    Department of Cell Biology, Division of Vascular Biology, The Scripps Research Institute, La Jolla, California, 92037, USA
    J Neurosci 26:13017-24. 2006
    ..Our results suggest that cell-surface-expressed forms of actin bind plasminogen, thereby promoting plasminogen activation and increased prohormone processing leading to inhibition of neurotransmitter release...
  18. pmc Plasminogen activator Pla of Yersinia pestis utilizes murine DEC-205 (CD205) as a receptor to promote dissemination
    Shu sheng Zhang
    Department of Biomedical Sciences, College of Medicine Rockford, University of Illinois at Chicago, Rockford, Illinois 61107, USA
    J Biol Chem 283:31511-21. 2008
    ..pestis in mice. In conclusion, murine DEC-205 is a receptor for PLA of Y. pestis, and this host-pathogen interaction appears to play a key role in promoting bacterial dissemination...
  19. pmc The single substitution I259T, conserved in the plasminogen activator Pla of pandemic Yersinia pestis branches, enhances fibrinolytic activity
    Johanna Haiko
    General Microbiology, Faculty of Biosciences, FI 00014 University of Helsinki, Finland
    J Bacteriol 191:4758-66. 2009
    ..The results suggest that Microtus Pla represents an ancestral form of Pla that has evolved into a more efficient plasminogen activator in the pandemic Y. pestis lineages...
  20. ncbi Physiological consequences of loss of plasminogen activator gene function in mice
    P Carmeliet
    Whitehead Institute of Biomedical Research, Cambridge, Massachusetts 02142
    Nature 368:419-24. 1994
    ..Mice with combined t-PA and u-PA deficiency suffer extensive spontaneous fibrin deposition, with its associated effects on growth, fertility and survival...
  21. pmc Rac mediates cytoskeletal rearrangements and increased cell motility induced by urokinase-type plasminogen activator receptor binding to vitronectin
    L Kjøller
    Medical Research Council Laboratory for Molecular Cell Biology, Cancer Research Campaign Oncogene and Signal Transduction Group, University College London, United Kingdom
    J Cell Biol 152:1145-57. 2001
    ..This mechanism may play a role in uPAR-mediated regulation of cell motility at sites where VN and uPAR are co-expressed, such as malignant tumors...
  22. ncbi Reduced metastasis of transgenic mammary cancer in urokinase-deficient mice
    Kasper Almholt
    Finsen Laboratory, Rigshospitalet 8621, Strand boulevarden 49, DK 2100 Copenhagen, Denmark
    Int J Cancer 113:525-32. 2005
    ..We show that metastasis is strongly and selectively decreased in uPA-deficient mice, suggesting that uPA-directed antimetastatic therapy would be efficacious and have limited side effects...
  23. ncbi Activation of pro-matrix metalloproteinase-9 and degradation of gelatin by the surface protease PgtE of Salmonella enterica serovar Typhimurium
    Päivi Ramu
    General Microbiology, Department of Biological and Environmental Sciences, Faculty of Biosciences, University of Helsinki, PO Box 56, FIN 00014 Helsinki, Finland
    Int J Med Microbiol 298:263-78. 2008
    ..Our results indicate that PgtE and Pla have diverged in substrate specificity, and suggest that Salmonella PgtE has evolved to functionally mimic mammalian MMPs...
  24. ncbi Collagen dissolution by keratinocytes requires cell surface plasminogen activation and matrix metalloproteinase activity
    Sarah Netzel-Arnett
    Matrix Metalloproteinase Unit, NIDCR, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 277:45154-61. 2002
    ..We propose that plasminogen activation facilitates keratinocyte-mediated collagen breakdown via the direct activation of matrix metalloproteinase-13 and possibly other fibrillar collagenases...
  25. ncbi Invited review: Breaking barriers--attack on innate immune defences by omptin surface proteases of enterobacterial pathogens
    Johanna Haiko
    General Microbiology, Faculty of Biosciences, University of Helsinki, Helsinki, Finland
    Innate Immun 15:67-80. 2009
    ..Modification of lipopolysaccharide by in vivo conditions or by bacterial gene loss has an impact on omptin function. Creation of bacterial surface proteolysis is thus a coordinated function involving several surface structures...
  26. pmc Temperature-induced changes in the lipopolysaccharide of Yersinia pestis affect plasminogen activation by the pla surface protease
    Marjo Suomalainen
    Department of Biosciences, FIN 00014 University of Helsinki, Helsinki, Finland
    Infect Immun 78:2644-52. 2010
    ..The temperature-induced changes in LPS are known to help Y. pestis to avoid innate immune responses, and our results strongly suggest that they also potentiate Pla-mediated proteolysis...
  27. ncbi Osteopontin modulates prostate carcinoma invasive capacity through RGD-dependent upregulation of plasminogen activators
    Adriano Angelucci
    Department of Experimental Medicine, University of L Aquila, Italy
    Biol Chem 383:229-34. 2002
    ..The pattern of protease expression was modified by osteopontin and was characterized by an upregulation of plasminogen activators. Our findings suggest that osteopontin may confer selective malignant potential to prostate cancer cells ..
  28. ncbi Human single-chain urokinase is activated by the omptins PgtE of Salmonella enterica and Pla of Yersinia pestis despite mutations of active site residues
    Hanna M Järvinen
    Division of General Microbiology, Department of Biosciences, University of Helsinki, P O Box 56, FI, 00014, Finland
    Mol Microbiol 89:507-17. 2013
    ..Point mutations of active site residues in Pla and PgtE had different effects on the proteolysis of plasminogen and of scuPA, indicating versatility in omptin proteolysis. ..
  29. ncbi Protein regions important for plasminogen activation and inactivation of alpha2-antiplasmin in the surface protease Pla of Yersinia pestis
    M Kukkonen
    Division of General Microbiology, Department of Biosciences, University of Helsinki, Finland
    Mol Microbiol 40:1097-111. 2001
    ..We propose that inactivation of alpha2-antiplasmin by Pla of Y. pestis promotes uncontrolled proteolysis and contributes to the invasive character of plague...
  30. ncbi Bacterial plasminogen activators and receptors
    K Lähteenmäki
    Division of General Microbiology, Department of Biosciences, University of Helsinki, P O Box 56, FIN 00014 Helsinki, Finland
    FEMS Microbiol Rev 25:531-52. 2001
    ..plasmin(ogen) on the bacterial surface, an event that enhances activation of plasminogen by mammalian plasminogen activators. Bacteria also influence secretion of plasminogen activators and their inhibitors from mammalian cells...
  31. pmc Plasminogen binding and activation at the surface of Helicobacter pylori CCUG 17874
    M Pantzar
    Department of Medical Microbiology, University of Lund, Lund, Sweden
    Infect Immun 66:4976-80. 1998
    ....
  32. ncbi Induction of matrix metalloproteinase, cytokines and chemokines in rat cortical astrocytes exposed to plasminogen activators
    Sun Ryung Lee
    Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
    Neurosci Lett 417:1-5. 2007
    b>Plasminogen activators are used in thrombolytic stroke therapy. However, it is increasingly recognized that they have other actions besides fibrinolysis...
  33. ncbi Interaction between group A streptococci and the plasmin(ogen) system promotes virulence in a mouse skin infection model
    Z Li
    Laboratory of Pathology, Division of Clincal Science, NCI NIH, Bethesda, MD 20895 1500
    J Infect Dis 179:907-14. 1999
    ..These results support the hypothesis that acquisition of a surface-associated plasmin(ogen)-dependent enzymatic activity can contribute to the virulence of group A streptococcal invasive infections...
  34. ncbi Differential effects of nonsteroidal antiinflammatory drugs on the IL-1 altered expression of plasminogen activators and plasminogen activator inhibitor-1 by articular chondrocytes
    T Sadowski
    Institute of Pharmacology and Toxicology, University of Bonn, Germany
    Inflamm Res 51:427-33. 2002
    ..To determine the in vitro effects of several nonsteroidal antiinflammatory drugs on the IL-1 altered expression and activity of tPA, uPA and PAI-1 by articular chondrocytes...
  35. pmc Accessibility of receptor-bound urokinase to type-1 plasminogen activator inhibitor
    M V Cubellis
    Institute of Microbiology, University of Copenhagen, Denmark
    Proc Natl Acad Sci U S A 86:4828-32. 1989
    ..The possibility that in adherent cells a different localization of PAI-1 and uPA leads to protection of uPA from PAI-1 is to be considered...
  36. ncbi Fibrin binding and the regulation of plasminogen activators during thrombolytic therapy
    C Longstaff
    Biotherapeutics Division, NIBSC, S Mimms, Herts, EN6 3QG, UK
    Cardiovasc Hematol Agents Med Chem 6:212-23. 2008
    ....
  37. pmc The fibrinolytic system in dissemination and matrix protein deposition during a mycobacterium infection
    Jun Sato
    W M Keck Center for Transgene Research and the Department of Chemistry, University of Notre Dame, Notre Dame, Indiana, IN 46556, USA
    Am J Pathol 163:517-31. 2003
    ..avium from lungs. Thus, plasmin(ogen) functions in limiting progressive fibrosis in the granuloma during a chronic mycobacterial infection...
  38. ncbi Roles of the plasminogen activator streptokinase and the plasminogen-associated M protein in an experimental model for streptococcal impetigo
    Mikael D Svensson
    Department of Laboratory Medicine, Lund University, Lund, Sweden
    Microbiology 148:3933-45. 2002
    ..An integrated model for superficial infection at the skin is presented...
  39. ncbi Lack of O-antigen is essential for plasminogen activation by Yersinia pestis and Salmonella enterica
    Maini Kukkonen
    Division of General Microbiology, Department of Biosciences, FIN 00014 University of Helsinki, Helsinki, Finland
    Mol Microbiol 51:215-25. 2004
    ..Loss of O-antigen facilitates Pla functions and invasiveness of Y. pestis; on the other hand, smooth LPS renders plasminogen activator cryptic in S. enterica...
  40. ncbi Role of MMPs and plasminogen activators in angiogenesis after transmyocardial laser revascularization in dogs
    Wei Li
    Second Department of Surgery, Fukui Medical University, Japan
    Am J Physiol Heart Circ Physiol 284:H23-30. 2003
    ..We conclude that TMLR induces the expression of MMPs, TIMPs, and urokinase-type PA and that these proteinases play an important role in angiogenesis after TMLR...
  41. ncbi Serine-proteases as plasminogen activators in terms of fibrinolysis
    Martin Flemmig
    Institute of Pharmacy, Freie Universitat Berlin, Berlin, Germany
    J Pharm Pharmacol 64:1025-39. 2012
    This review should give an overview about the natural human plasminogen activators and their various modified variants as well as similar substances isolated from animals, microorganisms and plants...
  42. ncbi The omptin family of enterobacterial surface proteases/adhesins: from housekeeping in Escherichia coli to systemic spread of Yersinia pestis
    Maini Kukkonen
    General Microbiology, Faculty of Biosciences, University of Helsinki, P O Box 56 Viikinkaari 9, FIN 00014 Helsinki, Finland
    Int J Med Microbiol 294:7-14. 2004
    ....
  43. pmc Molecular adaptation of a plant-bacterium outer membrane protease towards plague virulence factor Pla
    Johanna Haiko
    Division of General Microbiology, Department of Biosciences, P, O, Box 56, FI 00014 University of Helsinki, Finland
    BMC Evol Biol 11:43. 2011
    ..We addressed three virulence-associated functions exhibited by Pla, i.e., proteolytic activation of plasminogen, proteolytic degradation of serine protease inhibitors, and invasion into human cells...
  44. ncbi Genetic analysis of Streptococcus uberis plasminogen activators
    Philip N Ward
    Institute for Animal Health, Compton Laboratory, Compton, Berkshire, RG20 7NN, UK
    Indian J Med Res 119:136-40. 2004
    Streptococci produce a diverse range of secreted plasminogen activators capable of converting mammalian plasminogen to plasmin in a species-specific manner...
  45. ncbi Elevation of plasminogen activators in cerebrospinal fluid of mice with eosinophilic meningitis caused by Angiostrongylus cantonensis
    Roger F Hou
    Department of Entomology, National Chung Hsing University, Taichung 402, Taiwan, ROC
    Int J Parasitol 34:1355-64. 2004
    ..These results suggest that tissue-type plasminogen activator and urokinase-type plasminogen activator may be play a role in the pathogenesis of eosinophilic meningitis of angiostrongyliasis...
  46. ncbi Binding of human single chain urokinase to Chinese Hamster Ovary cells and cloning of hamster u-PAR
    B Fowler
    Department of Vascular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
    Thromb Haemost 80:148-54. 1998
    ..In addition, the results of our studies suggest that the hamster may be a useful small animal model for studies of human urokinase function...
  47. ncbi Plasminogen activators and their inhibitor gene expression in cutaneous NF1-related neurofibromas
    Vappu Sirén
    Haartman Institute, University of Helsinki, P O Box 21, 00014, Helsinki, Finland
    Arch Dermatol Res 297:421-4. 2006
    ..We wanted to study plasminogen activators, urokinase (uPA) and tissue type (tPA) and their inhibitor PAI-1, which have not earlier been studied ..
  48. ncbi Effects of nicotine and lipopolysaccharide on the expression of matrix metalloproteinases, plasminogen activators, and their inhibitors in human osteoblasts
    Tomoko Katono
    Nihon University Graduate School of Dentistry, 1 8 13, Kanda Surugadai, Chiyoda ku, Tokyo 101 8310, Japan
    Arch Oral Biol 54:146-55. 2009
    ..We examined the effects of nicotine and LPS on the expression of matrix metalloproteinases (MMPs), plasminogen activators (PAs), and their inhibitors, including tissue inhibitors of metalloproteinases (TIMPs) and PA inhibitor-1 (..
  49. ncbi CSF levels of growth factors and plasminogen activators in leptomeningeal metastases
    B van de Langerijt
    Department of Neurology, Laboratory of Pediatrics and Neurology, Radboud University Nijmegen Medical Centre, 830 LKN, P O Box 9101, 6500 HB Nijmegen, The Netherlands
    Neurology 67:114-9. 2006
    ....
  50. pmc Fibrin facilitates both innate and T cell-mediated defense against Yersinia pestis
    Deyan Luo
    Trudeau Institute, Saranac Lake, NY 12983, USA
    J Immunol 190:4149-61. 2013
    ..The data suggest that T cells combat plague in conjunction with neutrophils, which require help from fibrin to withstand Y. pestis encounters and effectively clear bacteria...
  51. ncbi Plasminogen activators and plasminogen activator inhibitors in endometriosis
    Juan Gilabert-Estelles
    Department of Gynecology Human Reproduction, Hospital Universitario La Fe, Valencia, Spain
    Front Biosci 10:1162-76. 2005
    ..Proteolytic status is determined by the imbalance between plasminogen activators and plasminogen activator inhibitors, which are expressed differently depending on the type of lesion ..
  52. ncbi Levels of plasminogen activators and their inhibitors in maternal and umbilical cord plasma in severe preeclampsia
    Eva Maria Roes
    Departments of Obstetrics and Gynecology, University Medical Center Nijmegen, Geert Grooteplein 8, 6525 GA Nijmegen, The Netherlands
    Am J Obstet Gynecol 187:1019-25. 2002
    ..The purpose of this study was to evaluate the plasminogen activator system in maternal and umbilical cord plasma in patients with severe preeclampsia compared with control subjects with normotensive pregnancies...
  53. ncbi Functional roles of streptokinase C-terminal flexible peptide in active site formation and substrate recognition in plasminogen activation
    Peng Zhai
    Crystallography Research Program, Oklahoma Medical Research Foundation, 825 Northeast 13th Street, Oklahoma City, Oklahoma 73104, USA
    Biochemistry 42:114-20. 2003
    ..Attempts at using a purified C-tail peptide to rescue the activity loss of the truncation mutants failed, suggesting that the integrity of the SK C-terminal peptide is important for the full function of SK...
  54. ncbi Thrombin-activatable fibrinolysis inhibitor is degraded by Salmonella enterica and Yersinia pestis
    M Valls Seron
    Experimental Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
    J Thromb Haemost 8:2232-40. 2010
    ..Thrombin-activatable fibrinolysis inhibitor (TAFI) has anti-fibrinolytic properties as the active enzyme (TAFIa) removes C-terminal lysine residues from fibrin, thereby attenuating accelerated plasmin formation...
  55. ncbi Effects of tetracyclines on the production of matrix metalloproteinases and plasminogen activators as well as of their natural inhibitors, tissue inhibitor of metalloproteinases-1 and plasminogen activator inhibitor-1
    T Sadowski
    Institute of Pharmacology and Toxicology, University of Bonn, Germany
    Inflamm Res 50:175-82. 2001
    ..effects on the expression of MMP-1, MMP-3, tissue inhibitor(s) of metalloproteinase-1 (TIMP-1), plasminogen activators (PA), and PA inhibitor-1, which are all involved in the ultimate regulation of MMP activity could provide ..
  56. ncbi Role of plasminogen activators during healing after uterine serosal lesioning in the rat
    Ujjwal Kumar Rout
    C S Mott Center for Human Growth and Development, Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, Michigan 48201, USA
    Fertil Steril 79:138-45. 2003
    Study the expression pattern of tissue-type (t-PA) and urokinase-type (u-PA) plasminogen activators during uterine serosal healing after lesioning in a rat model.
  57. ncbi The plasmin-antiplasmin system: structural and functional aspects
    Johann Schaller
    Department of Chemistry and Biochemistry, University of Bern, Freiestrasse 3, Bern, Switzerland
    Cell Mol Life Sci 68:785-801. 2011
    ..The activity of the plasminogen activators is primarily regulated by the plasminogen activator inhibitors 1 and 2, members of the serine protease ..
  58. pmc Proteolytic inactivation of tissue factor pathway inhibitor by bacterial omptins
    Thomas H Yun
    Department of Biochemistry, College of Medicine, University of Illinois at Urbana Champaign, IL 61801, USA
    Blood 113:1139-48. 2009
    ..This may contribute to the hemostatic imbalance in disseminated intravascular coagulation and other coagulopathies accompanying severe sepsis...
  59. ncbi Plasmin-dependent and -independent effects of plasminogen activators and inhibitor-1 on ex vivo angiogenesis
    S Brodsky
    Department of Medicine, State University of New York, Stony Brook, New York 11794 8152, USA
    Am J Physiol Heart Circ Physiol 281:H1784-92. 2001
    ....
  60. ncbi Vampire bat salivary plasminogen activator (desmoteplase): a unique fibrinolytic enzyme that does not promote neurodegeneration
    Gabriel T Liberatore
    Department of Medicine, Monash University, Box Hill Hospital, Victoria, Australia
    Stroke 34:537-43. 2003
    ..The purpose of this study was to compare the ability of DSPA and tPA to promote kainate- and N-methyl-D-aspartate (NMDA)-induced neurodegeneration in tPA-/- mice and wild-type mice, respectively...
  61. ncbi Plasminogen activators and their inhibitors in human saliva and salivary gland tissue
    Oskari J Virtanen
    Department of Virology, Haartman Institute, University of Helsinki, Finland
    Eur J Oral Sci 114:22-6. 2006
    The purpose of this study was to identify plasminogen activators (PA) and their specific inhibitors in human cell-free saliva and to investigate their expression in salivary gland tissue...
  62. pmc Role of the Yersinia pestis plasminogen activator in the incidence of distinct septicemic and bubonic forms of flea-borne plague
    Florent Sebbane
    Laboratory of Zoonotic Pathogens and Veterinary Branch, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA
    Proc Natl Acad Sci U S A 103:5526-30. 2006
    ..Subsequent acquisition of the plasminogen activator gene by horizontal transfer enabled the bubonic form of disease and increased the potential for epidemic spread...
  63. pmc Mannose 6-phosphate/insulin-like growth factor-II receptor targets the urokinase receptor to lysosomes via a novel binding interaction
    A Nykjaer
    Department of Medical Biochemistry, University of Aarhus, DK 8000 Aarhus, Denmark
    J Cell Biol 141:815-28. 1998
    ..We conclude that a site within CIMPR, distinct from its previously known ligand binding sites, binds uPAR and modulates its subcellular distribution...
  64. ncbi Plasminogen activation by invasive human pathogens
    M D Boyle
    Department of Microbiology, Medical College of Ohio, Toledo 43699 0008, USA
    Thromb Haemost 77:1-10. 1997
    ..the interaction between invasive human pathogens expressing plasmin(ogen) receptors and/or producing plasminogen activators with the human plasmin(ogen) system is described...
  65. ncbi The receptor-binding sequence of urokinase. A biological function for the growth-factor module of proteases
    E Appella
    J Biol Chem 262:4437-40. 1987
    ..Thus, residues 20-30 of uPA apparently confer receptor binding specificity, and residues 13-19 provide the proper conformation to the adjacent binding region...
  66. pmc The receptor for urokinase type plasminogen activator polarizes expression of the protease to the leading edge of migrating monocytes and promotes degradation of enzyme inhibitor complexes
    A Estreicher
    Institute of Histology and Embryology, University of Geneva Medical School, Switzerland
    J Cell Biol 111:783-92. 1990
    ....
  67. ncbi Transforming growth factor beta1 in the human endometrium. Cyclic variation, increased expression by estradiol and progesterone, and regulation of plasminogen activators and plasminogen activator inhibitor-1
    B Casslen
    Department of Obstetrics and Gynecology, University Hospital, Lund, Sweden
    Biol Reprod 58:1343-50. 1998
    ..TGFbeta may promote capillary growth during endometrial regeneration...
  68. ncbi Neuronal extracellular proteases facilitate cell migration, axonal growth, and pathfinding
    N W Seeds
    Department of Biochemistry and Molecular Genetics, and Neuroscience Center, University of Colorado Health Sciences Center, Denver, CO 80262, USA
    Cell Tissue Res 290:367-70. 1997
    ..We discuss recent findings that suggest that the biological action of these proteases is more complex than originally thought...
  69. ncbi Enolases from Gram-positive bacterial pathogens and commensal lactobacilli share functional similarity in virulence-associated traits
    Jenni Antikainen
    General Microbiology, Faculty of Biosciences, University of Helsinki, Helsinki, Finland
    FEMS Immunol Med Microbiol 51:526-34. 2007
    ..e., binding of human plasminogen, enhancement of plasminogen activation by human plasminogen activators, as well as binding to immobilized laminin, fibronectin and collagens...
  70. ncbi Bacterial metastasis: the host plasminogen system in bacterial invasion
    Kaarina Lähteenmäki
    General Microbiology, Faculty of Biosciences, University of Helsinki, FIN 00014 Helsinki, Finland
    Trends Microbiol 13:79-85. 2005
    ..system by degrading circulating plasmin inhibitors and by influencing the expression levels of mammalian plasminogen activators and activation inhibitors...
  71. ncbi Plasminogen receptors: the sine qua non of cell surface plasminogen activation
    Lindsey A Miles
    Department of Cell Biology, Division of Vascular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
    Front Biosci 10:1754-62. 2005
    Localization of plasminogen and plasminogen activators on cell surfaces promotes plasminogen activation and serves to arm cells with the broad spectrum proteolytic activity of plasmin...
  72. ncbi The serpin PAI-1 inhibits cell migration by blocking integrin alpha V beta 3 binding to vitronectin
    S Stefansson
    Biochemistry Department, J H Holland Laboratory, American Red Cross, Rockville, Maryland 20855, USA
    Nature 383:441-3. 1996
    ..wound healing, migrating cells increase expression of both the vitronectin receptor (VNR) integrins and plasminogen activators. Here we report that vitronectin significantly enhances the migration of smooth muscle cells (SMCs), and ..
  73. ncbi The safety, efficacy, and pharmacoeconomics of low-dose alteplase compared with urokinase for catheter-directed thrombolysis of arterial and venous occlusions
    Koji Sugimoto
    Division of Cardiovascular Interventional Radiology, Stanford University Medical Center, Stanford, California, USA
    J Vasc Surg 37:512-7. 2003
    ....
  74. ncbi Inhibition of plasminogen activators or matrix metalloproteinases prevents cardiac rupture but impairs therapeutic angiogenesis and causes cardiac failure
    S Heymans
    Center for Transgene Technology, Flanders Interuniversity, Leuven, Belgium
    Nat Med 5:1135-42. 1999
    ....
  75. pmc Plasminogen activators and inhibitor type 1 in neoplastic colonic tissue from patients with familial adenomatous polyposis
    C F Sier
    Department of Gastroenterology and Hepatology, University Hospital, Leiden, The Netherlands
    Br J Cancer 71:393-6. 1995
    The plasminogen activation cascade is involved in carcinogenesis, invasion and metastasis. In this study plasminogen activators and their type 1 inhibitor were evaluated in colonic tissue from 19 patients with familial adenomatous ..
  76. pmc Substrate specificity and screening of the integral membrane protease Pla
    Anton Agarkov
    Chemical Biology Program, Department of Pharmacology and Toxicology, The University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555 0650, USA
    Bioorg Med Chem Lett 18:427-31. 2008
    ..Through the use of parallel synthesis and positional scanning, small tripeptides were identified that are viable substrates for the protease...
  77. ncbi Concentration of plasminogen activators and inhibitor in the human endometrium at different phases of the menstrual cycle
    S C Koh
    Department of Obstetrics and Gynaecology, National University of Singapore, National University Hospital
    J Reprod Fertil 96:407-13. 1992
    ..Ovarian hormonal patterns may therefore influence the activity of plasminogen activators especially of t-PA in the endometrium during various phases of the menstrual cycle.
  78. pmc Urokinase receptor (CD87) regulates leukocyte recruitment via beta 2 integrins in vivo
    A E May
    Haemostasis Research Unit, Max Planck Institute, Kerckhoff Klinik, D 61231 Bad Nauheim, Germany
    J Exp Med 188:1029-37. 1998
    ..Moreover, uPAR ligation differentially modulates leukocyte adhesion to endothelium and provides novel targets for therapeutic strategies in inflammation-related vascular pathologies...
  79. ncbi Expression of protease nexin-1 and plasminogen activators during follicular growth and the periovulatory period in cattle
    Mingju Cao
    Centre de Recherche en Reproduction Animale, CRRA, Faculte de Medecine Veterinaire, Universite de Montreal, C P 5000 St Hyacinthe, Quebec, Canada
    Reproduction 131:125-37. 2006
    Extracellular matrix remodeling occurs during ovarian follicular development, mediated by plasminogen activators (PAs) and PA inhibitors including protease nexin-1 (PN-1)...
  80. ncbi Differences in the implantation rates of rat embryos developed in vivo and in vitro: possible role for plasminogen activators
    Eliahu D Aflalo
    Department of Life Sciences, Ben Gurion University of the Negev, PO Box 653, Beer Sheva 84105, Israel
    Fertil Steril 81:780-5. 2004
    To assess the participation of urokinase-type (uPA) and tissue-type (tPA) plasminogen activators in embryo development and implantation.
  81. ncbi Clinical impact of the plasminogen activation system in tumor invasion and metastasis: prognostic relevance and target for therapy
    M Schmitt
    Frauenklinik und Poliklinik, Technischen Universitat Munchen, Germany
    Thromb Haemost 78:285-96. 1997
    ....
  82. ncbi Keeping the blood flowing-plasminogen activator genes and feeding behavior in vampire bats
    Asa Tellgren-Roth
    Department of Molecular Biology, University of Wyoming, Laramie, WY, 82071, USA
    Naturwissenschaften 96:39-47. 2009
    ..The evolution of vampire bat plasminogen activators can now be linked phylogenetically to the transition in feeding behavior among vampire bat species from ..
  83. ncbi Effect of ultrasound on enzymatic activity of selected plasminogen activators
    Azita Soltani
    Pre Clinical Research Department, EKOS Corporation, 22030 20th Avenue SE, Suite 101, Bothell, WA 98021, USA
    Thromb Res 119:223-8. 2007
    Ultrasound has been shown to accelerate enzymatic fibrinolysis with adjunctive plasminogen activators. Additionally, ultrasound is known for interaction with biological substances on molecular level in sonodynamic therapy and ..
  84. ncbi uPAR: a versatile signalling orchestrator
    Francesco Blasi
    Department of Molecular Biology and Functional Genomics, DIBIT, Universita Vita Salute San Raffaele, Via Olgettina 58, 20132 Milano, Italy
    Nat Rev Mol Cell Biol 3:932-43. 2002
    ....
  85. ncbi Metalloproteinases and plasminogen activators in vessel remodeling
    Alex Bobik
    Cell Biology Laboratory, Baker Heart Research Institute, PO Box 6492, St Kilda Road Central, Melbourne Victoria 8008, Australia
    Curr Hypertens Rep 5:466-72. 2003
    ....
  86. pmc Is plasminogen activator inhibitor-1 the molecular switch that governs urokinase receptor-mediated cell adhesion and release?
    G Deng
    Department of Vascular Biology, Scripps Research Institute, La Jolla, California 92037, USA
    J Cell Biol 134:1563-71. 1996
    ..Finally, we show that uPA can rapidly reverse this effect of PAI-1. Taken together, these results suggest a dynamic regulatory role for PAI-1 and uPA in uPAR-mediated cell adhesion and release...
  87. pmc Capsular antigen fraction 1 and Pla modulate the susceptibility of Yersinia pestis to pulmonary antimicrobial peptides such as cathelicidin
    Estela M Galván
    Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, 3800 Spruce Street, Philadelphia, PA 19104, USA
    Infect Immun 76:1456-64. 2008
    ..Taken together, our data indicated that Pla might act as a virulence factor not only by processing plasminogen but also by inactivating CAMPs, particularly when F1 is not expressed...
  88. ncbi Staphylokinase reduces plasmin formation by endogenous plasminogen activators
    Tao Jin
    Department of Rheumatology and Inflammation Research, Sahlgrenska University Hospital, Goteborg, Sweden
    Eur J Haematol 81:8-17. 2008
    ..Increased levels of circulating plasminogen (Plg) activators such as tissue- or urokinase-type plasminogen activators (tPA or uPA respectively) are the most common causes of hyperfibrinolysis, occasionally causing major ..
  89. ncbi A plasminogen-activating protease specifically controls the development of primary pneumonic plague
    Wyndham W Lathem
    Department of Molecular Microbiology, Washington University School of Medicine, St Louis, MO 63110, USA
    Science 315:509-13. 2007
    ..Inhibition of Pla expression prolonged the survival of animals with the disease, offering a therapeutic option to extend the period during which antibiotics are effective...
  90. ncbi In vitro and in vivo induction of antiangiogenic activity by plasminogen activators and captopril
    Jaime R Merchan
    Division of Hematology Oncology, Department of Medicine and the Center for Study of the Tumor Microenvironment, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA
    J Natl Cancer Inst 95:388-99. 2003
    Many antiangiogenic molecules are proteolytically cleaved from larger plasma proteins. For example, plasminogen activators cleave plasminogen into plasmin, and plasmin is converted into angiostatin in the presence of sulfhydryl donors...
  91. pmc Contribution of plasminogen activators and their inhibitors to the survival prognosis of patients with Dukes' stage B and C colorectal cancer
    S Ganesh
    Department of Gastroenterology and Hepatology, University Hospital Leiden, The Netherlands
    Br J Cancer 75:1793-801. 1997
    ....
  92. ncbi Role of plasminogen activator-plasmin system in tumor angiogenesis
    J M Rakic
    Department of Ophthalmology, CHU, Sart Tilman, 4000 Liege, Belgium
    Cell Mol Life Sci 60:463-73. 2003
    ..In this review, the complex mechanisms of action of the serine proteases in pathological angiogenesis are summarized alongside possible therapeutic applications...
  93. pmc Cloning and expression of the receptor for human urokinase plasminogen activator, a central molecule in cell surface, plasmin dependent proteolysis
    A L Roldan
    University Institute of Microbiology, Copenhagen, Denmark
    EMBO J 9:467-74. 1990
    ..The Mr calculated on the basis of the cDNA sequence, approximately 35,000, agrees well with that of the deglycosylated receptor...
  94. ncbi Urokinase and tissue plasminogen activators and their inhibitor PAI-1 in human tumors
    E S Gershtein
    N N Blokhin Cancer Research Center, Russian Academy of Medical Sciences
    Bull Exp Biol Med 131:67-72. 2001
    The content of urokinase and tissue plasminogen activators and their inhibitor PAI-1 in tumors and histologically intact tissues from patients with breast, ovarian, and non-small-cell lung cancer was measured by enzyme immunoassay...
  95. ncbi The Pla surface protease/adhesin of Yersinia pestis mediates bacterial invasion into human endothelial cells
    K Lähteenmäki
    Division of General Microbiology, Department of Biosciences, University of Helsinki, P O Box 56, FIN 00014 Helsinki, Finland
    FEBS Lett 504:69-72. 2001
    ..coli XL1(pMRK2), which expresses the omptin homolog from E. coli. The results identify Pla as an invasion protein of Y. pestis and show that the invasive function does not involve the proteolytic activity of Pla...
  96. ncbi Plasminogen activators: a comparison
    Dev B Baruah
    Department of Quality Assurance Techniques, Poona College of Pharmacy, Bharati Vidyapeeth Deemed University, Erandwane, Pune 411038, India
    Vascul Pharmacol 44:1-9. 2006
    ..Now a days several newer plasminogen activators with different pharmacokinetic and pharmacodynamic properties have been developed to treat thrombotic ..
  97. ncbi Overexpression of plasminogen activators in the nucleus accumbens enhances cocaine-, amphetamine- and morphine-induced reward and behavioral sensitization
    A Bahi
    Institute of Biochemistry, University of Fribourg, Fribourg, Switzerland
    Genes Brain Behav 7:244-56. 2008
    ..Taken together, these data add further evidence for a significant function of extracellular proteases tPA and uPA in addiction and suggest a differential role of plasminogen activators in this context.
  98. pmc Direct binding of occupied urokinase receptor (uPAR) to LDL receptor-related protein is required for endocytosis of uPAR and regulation of cell surface urokinase activity
    R P Czekay
    Department of Cellular and Molecular Medicine, San Diego, La Jolla, California 92093 0651, USA
    Mol Biol Cell 12:1467-79. 2001
    ....
  99. ncbi Doxycycline inhibits MMPs via modulation of plasminogen activators in focal cerebral ischemia
    Dorothe Burggraf
    Department of Neurology, Ludwig Maximilians University, Klinikum Grosshadern, Marchioninistr 15, 81377 Munich, Germany
    Neurobiol Dis 25:506-13. 2007
    ..Hemoglobin extravasation was also significantly reduced. Our results suggest that doxycycline may have a potential use as an anti-ischemic compound since it provides microvascular protection by inhibiting the plasminogen system...
  100. ncbi Endovascular management of acute extensive iliofemoral deep venous thrombosis caused by May-Thurner syndrome
    N H Patel
    Department of Radiology, Indiana University Medical Center, Indianapolis, USA
    J Vasc Interv Radiol 11:1297-302. 2000
    ..The authors report their experience on the treatment of acute extensive iliofemoral deep venous thrombosis (DVT) due to May-Thurner syndrome using endovascular techniques...
  101. ncbi Anti-tumor activity of a combination of plasminogen activator and captopril in a human melanoma xenograft model
    Renate R J de Groot-Besseling
    Department of Pathology, University Medical Center Nijmegen, Nijmegen, The Netherlands
    Int J Cancer 112:329-34. 2004
    ..Angiostatin is generated in vitro in a 2-step process. First, plasminogen is converted to plasmin by plasminogen activators. Next, plasmin excises the angiostatin fragment from plasminogen, a process requiring molecules that are ..

Research Grants71

  1. Autonomic, Endothelial, and Inflammatory Correlates of Sleep Duration
    MERCEDES RENEE CARNETHON; Fiscal Year: 2012
    ..Findings from this study will suggest mechanisms to explain the prior observed associations between sleep duration and CVD risk factors. ..
  2. Antiphospholipid antibodies and lupus: new molecular targets for treatment
    Emilio B Gonzalez; Fiscal Year: 2013
    ..These studies may help to devise new more specific and less harmful modalities than the anticoagulation or general immunosuppression currently used to treat and prevent thrombosis in patients with aPL Abs. ..
  3. Metabolic regulation of diabetic nephropathy
    Karen Block; Fiscal Year: 2013
    ..This work may have major therapeutic implications. ..
  4. Role of Matrix Metalloproteinase-1 in Endothelial Cell Senescence
    Catherine D Mao; Fiscal Year: 2010
    ....
  5. Regulation of factor VIII Levels and Activity by Members of LDL Receptor Family
    Dudley K Strickland; Fiscal Year: 2013
    ..that plays an important role in the catabolism of several ligands including apoE-enriched lipoproteins, plasminogen activators, and serpin-enzyme complexes...
  6. Inhibition of matrix proteases to sensitize medulloblastoma cells to radiation
    Andrei L Gartel; Fiscal Year: 2013
    ..The present study explores the usefulness of gene therapy to inhibit protease expression in conjunction with radiation for killing of medulloblastoma cells with lower toxicity. ..
  7. Inhibitors of the Y. pestis cell surface plasminogen activator for biodefense
    Marjorie H Barnes; Fiscal Year: 2010
    ..These new drugs will not be susceptible to existing resistance mechanisms and will provide a proof of principle for the efficacy of this therapeutic approach. ..
  8. MRI of Acute Vascular Injury and Hemorrhagic Transformation in Ischemic Stroke
    Robert A Knight; Fiscal Year: 2010
    ..e., BBB opening) and both will be functions of the variations in BBB associated proteins and/or brain swelling;and 2) the size of these changes are correlated over time, ROI, and treatment. ..
  9. Regulation of Signaling Receptor Activity by LRP-1
    Steven L Gonias; Fiscal Year: 2013
    ..PUBLIC HEALTH RELEVANCE: Low density lipoprotein receptor-related protein has emerged as an important regulator of inflammation and atherosclerosis. This proposal seeks to elucidate the responsible mechanisms. ..
  10. Caveolins in the Pathogenesis of Idiopathic Pulmonary Fibrosis
    Dan N Predescu; Fiscal Year: 2010
    ..End of Abstract) ..
  11. Regulation of Fibronectin Matrix Assembly by uPAR
    PAULA J MC KEOWN-LONGO; Fiscal Year: 2012
    ....
  12. PlGF-HIF1a-miRNA Axis in Sickle Pulmonary Hypertension
    Punam Malik; Fiscal Year: 2013
    ..These studies will likely provide new diagnostic bio-markers for assessment of PHT, and novel therapeutic targets for a disease that currently has few or no therapeutic options. ..
  13. Treatment of stroke with a clinically approved proteasome inhibitor
    Li Zhang; Fiscal Year: 2012
    ..Therefore, in the current application, we propose to investigate the neuroprotective effects of VELCADE alone and incombination with tPA and the mechanisms underlying the beneficial effects in aged rats after embolic stroke. ..
  14. Novel therapeutics for vesicants and toxic inhaled chemicals (U54)
    Carl W White; Fiscal Year: 2013
    ..Agent(s) found effective for CEES/NM would be evaluated in skin injury by SM. These approaches will identify promising rescue agents for skin and lung injury by toxic gases. ..
  15. Plasminogen activators and NMDA after brain injury
    William M Armstead; Fiscal Year: 2012
    ..We propose that plasminogen activators change the MAPK isoform expression/activation profile in an LRP dependent process to elicit both initial ..
  16. The Role of Vascular Innervation on Tissue-type Plasminogen Activator Release
    JAMES ANTHONY SHEERIN MULDOWNEY; Fiscal Year: 2013
    ..With the overwhelming prevalence of vascular disease nationally, and worldwide, new insights and strategies have the potential translate to a tremendous public health impact...
  17. Adjunctive Use of Apyrase to Fibrinolytic Therapy
    Ridong Chen; Fiscal Year: 2013
    ....
  18. Dichotomous Roles of Thrombin in Acetaminophen Hepatotoxicity
    ROBERT ANDREW ROTH; Fiscal Year: 2013
    ..Elucidating mechanisms by which APAP-induced liver injury progresses is essential for defining novel strategies to prevent liver failure in patients and for the general understanding of the pathogenesis of drug-induced liver injury. ..
  19. S-Nitrosylated Hemoglobin and Ischemic Brain Injury
    David Warner; Fiscal Year: 2010
    ..We will then examine whether this effect is important in reducing the amount of tissue damage and neurologic impairment caused by the stroke. ..
  20. Investigation of underlying mechanisms of sex differences in cerebral ischemia
    Chad S Siegel; Fiscal Year: 2010
    ..The overall goal of this proposal is to investigate mechanisms underlying sex differences in ischemic cell death. ..
  21. Renin-angiotensin and fibrinolysis interaction in humans
    NANCY JOAN BROWN; Fiscal Year: 2013
    ....
  22. Inflammation and Injury in Obesity Hypertension in African American Adolescents
    Bonita Falkner; Fiscal Year: 2010
    ..abstract_text> ..
  23. Cell Surface Plasminogen Activation and Hypertension
    Robert J Parmer; Fiscal Year: 2013
    ....
  24. Vitamin D deficiency and treatment in male veterans at risk for diabetes
    Elena Barengolts; Fiscal Year: 2013
    ....
  25. Plasminogen activator inhibitor-1 in tumor progression and metastasis
    Yves A DeClerck; Fiscal Year: 2013
    ..inhibitors (serpins) that controls the activation of plasminogen into plasmin by tissue and urokinase type plasminogen activators (tPA and uPA, respectively). In the past, PAI-1 was considered to be anti-tumorigenic...
  26. Role for tissue-type plasminogen activator in suppression of hepatic fibrosis
    Liang I Kang; Fiscal Year: 2013
    ..Since t-PA is already FDA-approved for clinical use, the impact of this project is tremendous in terms of potential expedited development of therapies for liver cirrhosis patients who currently have limited treatment options. ..
  27. Targeted Therapy of Triple Negative Breast Cancer Using Theranostic Nanoparticles
    Lily Yang; Fiscal Year: 2013
    ..Clinical impact: The proposed study addresses the urgent need in clinical management of TNBC to improve the survival of patients afflicted with TNBC. ..
  28. PAI-1 and Vitronectin in Failure of Coronary Revascularization
    William P Fay; Fiscal Year: 2013
    ..applicant): Plasminogen activator inhibitor-1 (PAI-1) is the primary inhibitor of tissue- and urinary-type plasminogen activators. Vitronectin (VN) is an adhesive glycoprotein present in extracellular matrix (ECM) and plasma that ..
  29. Interactions between CNS-specific human kallikreins and the PA system in inflamma
    Michael Blaber; Fiscal Year: 2009
    ..The goals of the proposal are to understand how such proteases are controlled and how this control can be manipulated to potentially treat diseases of the central nervous system. ..
  30. MATRIX MEDIATORS OF WOUND HEALING
    Paul J Higgins; Fiscal Year: 2010
    ..Our continued clarification of mechanistic controls on PAI-1 gene expression may lead to new targeted therapies for diseases in which excessive or non-resolving angiogenesis is a major pathogenic feature. ..
  31. Role of Fibrinolytic System in Vein Graft Remodeling
    William P Fay; Fiscal Year: 2013
    ..We anticipate that the information gained from our experiments will lead to new strategies to treat and prevent vein graft disease. ..
  32. Endogenous and exogenous protection of the BBB in stroke
    Richard F Keep; Fiscal Year: 2013
    ..This proposal examines natural defense mechanisms that may protect the blood-brain barrier, how to activate those mechanisms or prevent their inactivation therapeutically. ..
  33. Regulation of Transcriptional Activity of Hypoxia Inducible Factor 2
    Cheng Jun Hu; Fiscal Year: 2012
    ..Thus, HIF is good for tumor growth, but bad for our human being. Thus our research on controlling HIF activity has broad impact for all solid tumors. ..
  34. Technology to improve the assessment of tissue-associated protein biomarkers
    JEFFREY THOMAS MASON; Fiscal Year: 2013
    ..It will also facilitate the detection and prognostic assessment of breast tumors at earlier stages where clinical options are greatest and where treatment outcomes are most likely to be favorable. ..
  35. Mini-plasmin: Pre-Clinical Evaluation of a Novel Thrombolytic Strategy for Stroke
    Irina Y Sazonova; Fiscal Year: 2012
    ..In this project we propose a novel thrombolytic agent and plan to determine its efficacy for the treatment in an experimental model of thromboembolic cerebral ischemia. ..
  36. KLF2 as a regulator of endothelial cell biology
    MUKESH KUMAR JAIN; Fiscal Year: 2012
    ..abstract_text> ..
  37. Countermeasures for chlorine-induced airway fibrosis
    Gary W Hoyle; Fiscal Year: 2013
    ..This type of research is important because of concerns that U.S. civilians could be adversely affected by the accidental or intentional release of highly toxic chemicals such as chlorine. ..
  38. Regulation of Pal-1 in Atherosclerosis and Thrombosis
    Yolanda M Fortenberry; Fiscal Year: 2013
    ..This is particularly important, since to date, there are no PAI-1 inhibitors available for clinical use (End of Abstract) ..
  39. Ah Receptor Anatomy: Implications for Dioxin Toxicity
    CORNELIS JOHAN ELFERINK; Fiscal Year: 2011
    ..Parallels between humans and mice in the re- generative response, instills confidence that findings generated during these studies will be directly applicable to the human condition. ..
  40. Matrix Metalloproteinase Inhibitors in Stroke
    GARY ALLEN ROSENBERG; Fiscal Year: 2010
    ..The overall goal is to identify lead compounds that are patentable and can be used to obtain IND approval. Promising compounds would be useful for U01- funded clinical trials. ..
  41. Ac-SDKP for Treatment of Acute Stroke
    Zheng Gang Zhang; Fiscal Year: 2013
    ..These studies could potentially provide a new therapy to minimize the adverse effect of tPA on ischemic neurovascular damage, leading to improved neurological outcomes after acute stroke. ..
  42. Pathogenesis of Lymphangioleiomyomatosis
    Lucia Schuger; Fiscal Year: 2010
    ..We believe that the new knowledge obtained from these studies will help to better understand the pathogenesis of LAM and to devise novel therapeutic strategies to treat this disease. ..
  43. Interactions of Lipoproteins and Cells in Diabetes Mellitus
    RICHARD LOUIS KLEIN; Fiscal Year: 2013
    ..Collectively, these studies will elucidate for the first time the patterns of S1P metabolism in lipoproteins and in diabetes, and define the cellular and plasma mechanisms which mediate this metabolism. ..
  44. QD-BRET nanosensors for protease detection and imaging
    Jianghong Rao; Fiscal Year: 2012
    ..A sophisticated understanding of the differences of enzyme activity between tumor and normal tissues in living subjects will advance our understanding of cancer metastasis and help develop antimetastasis therapy. ..
  45. Transcranial Sonothrombolysis with Diagnostic Ultrasound
    Thilo Hoelscher; Fiscal Year: 2013
    ..Noninvasive 'Image-Guided Sonothrombolysis'at the bedside or even in the ambulance vehicle would be a major achievement in stroke therapy. ..
  46. Treatment and Risk Factor Determinants of Cardiovascular Outcomes in BARI 2D
    Maria Mori Brooks; Fiscal Year: 2013
    ..Such results would have important clinical implications for the treatment of the large and growing population of patients with type 2 diabetes and stable ischemic heart disease. ..
  47. Corneal Expression and Function of Slurp1
    SHIVALINGAPPA KOTTUR SWAMYNATHAN; Fiscal Year: 2013
    ..The anticipated outcomes will define a novel target for therapeutic intervention in managing inflammatory disorders of the ocular surface. ..
  48. Deleted in liver cancer 1 (DLC1) in liver development and disease
    Yi Ping Shih; Fiscal Year: 2013
    ..An understanding of the functional impact of DLC1 in liver development and disease progression will help find new early diagnosis or therapeutic targets for liver disease. ..
  49. Real-time imaging of tPA fluorescent hybrids in hippocampal neurons
    Janis E Lochner; Fiscal Year: 2011
    ..tPA-mediated extracellular proteolysis is also implicated in excitotoxic cell death and the neuronal degeneration associated with Alzheimer<s disease. ..
  50. Role of Hyperglycemia in Intracerebral Hemorrhage
    Edward P Feener; Fiscal Year: 2013
    ..This grant will examine the hypothesis that the direct effects of plasma kallikrein on hemostasis and peri-hematomal edema contribute to the poor ICH outcomes in diabetes and hyperglycemia. ..
  51. Urokinase plasminogen activator receptor associated protein and acute lung injury
    Michael Bundesmann; Fiscal Year: 2010
    ..It will help us understand how the lung coordinates several components of the repair process. ..
  52. Protease Pathways in the Gastrointestinal Tract
    Toni M Antalis; Fiscal Year: 2010
    ..abstract_text> ..
  53. Weibel-Palade Bodies: roles in thrombosis, inflammation and stroke
    Denisa D Wagner; Fiscal Year: 2013
    ..We will investigate how inhibition of a particular component of these vesicles could improve outcome in these major diseases. ..
  54. Role of the Plasminogen Activator Protease during Pneumonic Plague
    Wyndham W Lathem; Fiscal Year: 2013
    ..This project is designed to elucidate those mechanisms at a genetic and biochemical level, and may have implications for understanding how other bacterial pathogens affect thrombosis and fibrinolysis during infection as well. ..
  55. BMP Regulation of TGF-b2 in the Trabecular Meshwork
    Robert J Wordinger; Fiscal Year: 2012
    ..This study is relevant because it will examine the role of local growth factors in the control of eye pressure and may lead to new treatments for glaucoma. ..
  56. Vascular protection by epoxide hydrolase inhibition in cerebral ischemia
    Alexis N Simpkins; Fiscal Year: 2010
    ..We will also determine if SEH inhibition can decrease fibrosis by using histology and zymography. Elucidating the mechanism of SEH inhibition will aid in determining its potential therapeutic use in high risk patients. ..
  57. Ah receptor transcriptional regulation through a novel DNA binding site
    SHELLY RENEE WILSON; Fiscal Year: 2012
    ..abstract_text> ..
  58. Preclinical Development of a Novel Plaque-Regressing Therapy For Atherosclerosis
    Michael W Fanger; Fiscal Year: 2012
    ..Success would ultimately provide a profound medical advancement in treatment of atherosclerosis, a significant benefit to human health, and a dramatic reduction in the economic impact of the number one killer in America. ..
  59. Novel Methods for Dissolving Blood Clots
    GUY LELAND REED; Fiscal Year: 2013
    ..Upon completion of this Phase II project and transfer of commercialization responsibilities to our strategic partner, TSI will investigate the potential benefits of this platform technology to heart and stroke victims. ..
  60. US-China Collaborative Research on Stroke Imaging
    Jinyuan Zhou; Fiscal Year: 2013
    ..If the hypotheses are proven correct, we expect to have an additional marker that can be used for diagnosis and prognosis of stroke patients in the clinic. ..
  61. CLASSICAL AND ALTERNATIVE PATHWAYS OF FIBRINOLYSIS
    EDWARD FRANKLIN PLOW; Fiscal Year: 2013
    ..Taken together, these studies will define how plasminogen and its receptors function in biologically important responses. ..
  62. NEW FUNCTION SERPIN PAI 2 AS A REGULAR OF RB
    Toni Antalis; Fiscal Year: 2009
    ..At the completion of these aims, we anticipate having established the molecular basis for PAI-2 mediated cytoprotection and its importance to inflammation and innate immunity ..
  63. Suppression of glioma invasion by a bicistronic constuct
    JASTI RAO; Fiscal Year: 2007
    ..RESEARCH GRANT TABLE OF CONTENTS Page Numbers Face Page .................................................................................................................................................. 1 Description, ..
  64. VON WILLEBRAND FACTOR, FIBRINOLYSIS, & THE ENDOTHELIUM
    Karen Hamilton; Fiscal Year: 1991
    ....
  65. HEMOSTATIC EFFECTS OF FIBRINOLYTIC THERAPY
    BARBARA ALEVRIADOU; Fiscal Year: 2000
    ....
  66. PA/PLASMIN/GELATINASE CASCADE IN DIABETIC NEPHROPATHY
    WILLIAM BARICOS; Fiscal Year: 2000
    ....
  67. tPA Neurotoxicity in Hypoxic-Ischemia Encephalopathy
    Chia Yi Kuan; Fiscal Year: 2009
    ..results indicated that ischemia-hypoxia produces a rapid induction of tissue-type and urokinase-type plasminogen activators (tPA and uPA) that coincides with transient thrombosis...
  68. PLATELETS, PLATELET AGGREGATES & PLASMINOGEN ACTIVATION
    Joseph Loscalzo; Fiscal Year: 1991
    ..From these studies, we hope to gain insight into mechanisms by which vessel wall products facilitate dissolution of the platelet thrombi that are implicated in the pathogenesis of many vascular disorders...
  69. ENVIRONMENTAL MODULATION OF FIBRINOLYSIS INHIBITORS
    STEVEN GONIAS; Fiscal Year: 1992
    ..The major goal of this research program is to study the regulation of plasmin and plasminogen activators in experimental systems that model important "non-plasma" sites of fibrinolytic activity...
  70. A THECAL ROLE IN OVULATION
    KATHERINE ROBY; Fiscal Year: 1999
    ..The studies outlined in this proposal begin to assess the mechanism whereby TCDD blocks ovulation. ..
  71. PRESERVATION AND CARDIAC TRANSPLANT VASCULOPATHY
    David Pinsky; Fiscal Year: 2003
    ..These experiments will provide new insights into mechanisms by which early ischemic injury leads to early graft failure and TCAD, and proffer new strategies for prevention. ..