platelet glycoprotein gpiib iiia complex

Summary

Summary: Platelet membrane glycoprotein complex important for platelet adhesion and aggregation. It is an integrin complex containing INTEGRIN ALPHAIIB and INTEGRIN BETA3 which recognizes the arginine-glycine-aspartic acid (RGD) sequence present on several adhesive proteins. As such, it is a receptor for FIBRINOGEN; VON WILLEBRAND FACTOR; FIBRONECTIN; VITRONECTIN; and THROMBOSPONDINS. A deficiency of GPIIb-IIIa results in GLANZMANN THROMBASTHENIA.

Top Publications

  1. ncbi Reconstructing and deconstructing agonist-induced activation of integrin alphaIIbbeta3
    Jaewon Han
    Department of Medicine, University of California, San Diego, La Jolla, California 92093, USA
    Curr Biol 16:1796-806. 2006
  2. ncbi Structural basis for allostery in integrins and binding to fibrinogen-mimetic therapeutics
    Tsan Xiao
    The CBR Institute for Biomedical Research and Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston, Massachusetts 02115, USA
    Nature 432:59-67. 2004
  3. pmc Kindlin-2 (Mig-2): a co-activator of beta3 integrins
    Yan Qing Ma
    Department of Molecular Cardiology, Cleveland Clinic, Cleveland, OH 44195, USA
    J Cell Biol 181:439-46. 2008
  4. ncbi Talin binding to integrin beta tails: a final common step in integrin activation
    Seiji Tadokoro
    Department of Cell Biology, The Scripps Research Institute, The Burnham Institute, La Jolla, CA 92037, USA
    Science 302:103-6. 2003
  5. ncbi Evidence that the platelet integrin alphaIIb beta3 is regulated by the integrin-linked kinase, ILK, in a PI3-kinase dependent pathway
    Jean Max Pasquet
    UMR 5533 CNRS, Hopital Cardiologique du Haut Leveque, Pessac, France
    Thromb Haemost 88:115-22. 2002
  6. pmc Modulation of cell migration by integrin-mediated cytoskeletal linkages and ligand-binding affinity
    A Huttenlocher
    Department of Cell and Structural Biology, University of Illinois, Urbana 61801, USA
    J Cell Biol 134:1551-62. 1996
  7. ncbi The elegant platelet: signals controlling actin assembly
    J H Hartwig
    Hematology Division, Brigham and Women s Hospital, Boston, MA 02115, USA
    Thromb Haemost 82:392-8. 1999
  8. ncbi Signaling through platelet integrin alpha IIb beta 3: inside-out, outside-in, and sideways
    S J Shattil
    Department of Vascular Biology, Scripps Research Institute, La Jolla, CA 92037, USA
    Thromb Haemost 82:318-25. 1999
  9. ncbi Initiation of platelet adhesion by arrest onto fibrinogen or translocation on von Willebrand factor
    B Savage
    Roon Research Center for Arteriosclerosis and Thrombosis, Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, La Jolla, California 92037, USA
    Cell 84:289-97. 1996
  10. ncbi Coronary stenting plus platelet glycoprotein IIb/IIIa blockade compared with tissue plasminogen activator in acute myocardial infarction. Stent versus Thrombolysis for Occluded Coronary Arteries in Patients with Acute Myocardial Infarction Study Investiga
    A Schomig
    Deutsches Herzzentrum, 1 Medizinische Klinik rechts der Isar, Munich, Germany
    N Engl J Med 343:385-91. 2000

Research Grants

Detail Information

Publications262 found, 100 shown here

  1. ncbi Reconstructing and deconstructing agonist-induced activation of integrin alphaIIbbeta3
    Jaewon Han
    Department of Medicine, University of California, San Diego, La Jolla, California 92093, USA
    Curr Biol 16:1796-806. 2006
    ..Many different signaling molecules that regulate integrin affinity have been described, but a pathway that connects agonist stimulation to talin binding and activation has not been mapped...
  2. ncbi Structural basis for allostery in integrins and binding to fibrinogen-mimetic therapeutics
    Tsan Xiao
    The CBR Institute for Biomedical Research and Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston, Massachusetts 02115, USA
    Nature 432:59-67. 2004
    ..Allostery in the head thus disrupts interaction between the legs in a previously described low-affinity bent integrin conformation, and leg extension positions the high-affinity head far above the cell surface...
  3. pmc Kindlin-2 (Mig-2): a co-activator of beta3 integrins
    Yan Qing Ma
    Department of Molecular Cardiology, Cleveland Clinic, Cleveland, OH 44195, USA
    J Cell Biol 181:439-46. 2008
    ..Our results thus identify kindlin-2 as a novel regulator of integrin activation; it functions as a coactivator...
  4. ncbi Talin binding to integrin beta tails: a final common step in integrin activation
    Seiji Tadokoro
    Department of Cell Biology, The Scripps Research Institute, The Burnham Institute, La Jolla, CA 92037, USA
    Science 302:103-6. 2003
    ..Thus, regulated binding of talin to integrin beta tails is a final common element of cellular signaling cascades that control integrin activation...
  5. ncbi Evidence that the platelet integrin alphaIIb beta3 is regulated by the integrin-linked kinase, ILK, in a PI3-kinase dependent pathway
    Jean Max Pasquet
    UMR 5533 CNRS, Hopital Cardiologique du Haut Leveque, Pessac, France
    Thromb Haemost 88:115-22. 2002
    ..Thus ILK transiently associates with and phosphorylates beta3 in a PI3-kinase dependent manner suggesting that it participates at an intermediate stage in a critical mechanism for assuring large stable aggregates...
  6. pmc Modulation of cell migration by integrin-mediated cytoskeletal linkages and ligand-binding affinity
    A Huttenlocher
    Department of Cell and Structural Biology, University of Illinois, Urbana 61801, USA
    J Cell Biol 134:1551-62. 1996
    ..Further, we demonstrate a dominant effect of high affinity integrin in inhibiting migration regardless of the organization of adhesive complexes. These observations have potential implications for tumor metastasis and its therapy...
  7. ncbi The elegant platelet: signals controlling actin assembly
    J H Hartwig
    Hematology Division, Brigham and Women s Hospital, Boston, MA 02115, USA
    Thromb Haemost 82:392-8. 1999
    ..The temporal nature of this reaction makes the platelet one of the most useful cells in which to understand both the proteins and the signaling pathways that initiate cell shape changes mediated by the actin filament system of cells...
  8. ncbi Signaling through platelet integrin alpha IIb beta 3: inside-out, outside-in, and sideways
    S J Shattil
    Department of Vascular Biology, Scripps Research Institute, La Jolla, CA 92037, USA
    Thromb Haemost 82:318-25. 1999
  9. ncbi Initiation of platelet adhesion by arrest onto fibrinogen or translocation on von Willebrand factor
    B Savage
    Roon Research Center for Arteriosclerosis and Thrombosis, Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, La Jolla, California 92037, USA
    Cell 84:289-97. 1996
    ..This eventually allows activated alpha IIb beta 3 to arrest platelets onto vWF under conditions not permissive of direct binding to fibrinogen. The coupling of these different functions may be crucial for thrombogenesis...
  10. ncbi Coronary stenting plus platelet glycoprotein IIb/IIIa blockade compared with tissue plasminogen activator in acute myocardial infarction. Stent versus Thrombolysis for Occluded Coronary Arteries in Patients with Acute Myocardial Infarction Study Investiga
    A Schomig
    Deutsches Herzzentrum, 1 Medizinische Klinik rechts der Isar, Munich, Germany
    N Engl J Med 343:385-91. 2000
    ....
  11. ncbi Bivalirudin during primary PCI in acute myocardial infarction
    Gregg W Stone
    Columbia University Medical Center and the Cardiovascular Research Foundation, New York, NY 10022, USA
    N Engl J Med 358:2218-30. 2008
    ..The safety and efficacy of bivalirudin in high-risk patients are unknown...
  12. ncbi Calpain cleavage of the cytoplasmic domain of the integrin beta 3 subunit
    X Du
    Department of Vascular Biology, Scripps Research Institute, La Jolla, California 92037, USA
    J Biol Chem 270:26146-51. 1995
    ..Thus, calpain cleavage of the beta 3 cytoplasmic domain may provide a means to regulate integrin signaling functions...
  13. ncbi A structural mechanism of integrin alpha(IIb)beta(3) "inside-out" activation as regulated by its cytoplasmic face
    Olga Vinogradova
    Structural Biology Program, Cleveland, OH 44195, USA
    Cell 110:587-97. 2002
    ....
  14. pmc Integrin alpha IIb beta 3 in a membrane environment remains the same height after Mn2+ activation when observed by cryoelectron tomography
    Feng Ye
    Institute of Molecular Biophysics, Florida State University, Tallahassee, FL 32306 4380, USA
    J Mol Biol 378:976-86. 2008
    ..Thus, the result is inconsistent with the switchblade activation model...
  15. ncbi Global conformational rearrangements in integrin extracellular domains in outside-in and inside-out signaling
    Junichi Takagi
    The Center for Blood Research, Departments of Pathology and Pediatrics, Harvard Medical School, Boston, MA 02115, USA
    Cell 110:599-11. 2002
    ..Breakage of a C-terminal clasp between the alpha and beta subunits enhances Mn(2+)-induced unbending and ligand binding...
  16. ncbi Comparison of primary and facilitated percutaneous coronary interventions for ST-elevation myocardial infarction: quantitative review of randomised trials
    Ellen C Keeley
    Department of Internal Medicine, Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, TX 75390 9047, USA
    Lancet 367:579-88. 2006
    ..We undertook a meta-analysis of randomised controlled trials (published and unpublished) to compare facilitated and primary percutaneous coronary intervention...
  17. ncbi Abciximab suppresses the rise in levels of circulating inflammatory markers after percutaneous coronary revascularization
    A M Lincoff
    Department of Cardiology, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA
    Circulation 104:163-7. 2001
    ..001); and the rise in tumor necrosis factor-alpha levels was 100% less with abciximab therapy (P=0.112). By 4 weeks, most marker levels had returned to baseline, with no significant differences between placebo and abciximab groups...
  18. pmc Critical roles for the COOH-terminal NITY and RGT sequences of the integrin beta3 cytoplasmic domain in inside-out and outside-in signaling
    Xiaodong Xi
    Department of Pharmacology, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA
    J Cell Biol 162:329-39. 2003
    ....
  19. ncbi Effect of tirofiban before primary angioplasty on initial coronary flow and early ST-segment resolution in patients with acute myocardial infarction
    Donald E Cutlip
    Interventional Cardiology Section, Beth Israel Deaconess Medical Center, Boston, Massacusetts 02215, USA
    Am J Cardiol 92:977-80. 2003
    ..20). Patients receiving early tirofiban treatment were more likely to achieve complete (>70%) ST-segment resolution at 90 minutes (69% vs 44%, p = 0.07)...
  20. ncbi The GP IIb/IIIa inhibitor abciximab (c7E3) inhibits the binding of various ligands to the leukocyte integrin Mac-1 (CD11b/CD18, alphaMbeta2)
    Meike Schwarz
    Department of Internal Medicine III, University of Freiburg, Freiburg, Germany
    Thromb Res 107:121-8. 2002
    ..Overall, the inhibition of Mac-1 could provide additional clinical benefits of abciximab beyond the well-described blockade of GP IIb/IIIa...
  21. ncbi Identification of a novel binding site for platelet integrins alpha IIb beta 3 (GPIIbIIIa) and alpha 5 beta 1 in the gamma C-domain of fibrinogen
    Nataly P Podolnikova
    Joseph J Jacobs Center for Thrombosis and Vascular Biology, Department of Molecular Cardiology, Lerner Research Institute, Cleveland, Ohio 44195, USA
    J Biol Chem 278:32251-8. 2003
    ..Thus, these data suggest that the P3 sequence in the gamma C-domain of fibrinogen defines a previously unknown recognition specificity of alpha IIb beta 3 and alpha 5 beta 1 and may function as a binding site for these integrins...
  22. ncbi Identification of a novel calcium-binding protein that interacts with the integrin alphaIIb cytoplasmic domain
    U P Naik
    Department of Pharmacology, Center for Thrombosis and Hemostasis, The University of North Carolina, Chapel Hill, North Carolina 27599, USA
    J Biol Chem 272:4651-4. 1997
    ..These results suggest that CIB is a candidate regulatory molecule for integrin alphaIIbbeta3...
  23. ncbi Amino acid residues in the alpha IIb subunit that are critical for ligand binding to integrin alpha IIbbeta 3 are clustered in the beta-propeller model
    T Kamata
    Department of Cell Biology, The Scripps Research Institute, La Jolla, California 92037, USA
    J Biol Chem 276:44275-83. 2001
    ..The results map an important ligand binding interface at the edge of the top and on the side of the beta-propeller toroid, centering on repeat 3...
  24. ncbi Bivalirudin for patients with acute coronary syndromes
    Gregg W Stone
    Columbia University Medical Center and the Cardiovascular Research Foundation, New York, NY 10022, USA
    N Engl J Med 355:2203-16. 2006
    ..We evaluated the role of thrombin-specific anticoagulation with bivalirudin in such patients...
  25. ncbi Genetic and pharmacological analyses of Syk function in alphaIIbbeta3 signaling in platelets
    D A Law
    COR Therapeutics, Inc, South San Francisco, CA, USA
    Blood 93:2645-52. 1999
    ....
  26. ncbi Fibrinogen binding to the integrin alpha(IIb)beta(3) modulates store-mediated calcium entry in human platelets
    J A Rosado
    Department of Physiology, University of Cambridge, Cambridge, United Kingdom
    Blood 97:2648-56. 2001
    ..This action may be important in intrinsic negative feedback to prevent the further activation of platelets subjected...
  27. ncbi Platelet glycoprotein IIb/IIIa receptor inhibition in non-ST-elevation acute coronary syndromes: early benefit during medical treatment only, with additional protection during percutaneous coronary intervention
    E Boersma
    Thoraxcenter, University Hospital Rotterdam, Netherlands
    Circulation 100:2045-8. 1999
    ..The question arises as to whether these 2 beneficial effects are independent and additive...
  28. ncbi Bruton's tyrosine kinase associates with the actin-based cytoskeleton in activated platelets
    S Mukhopadhyay
    Department of Biochemistry, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, India
    J Cell Biochem 81:659-65. 2001
    ..Taken together, these data suggest that Btk might be a component of a signaling complex containing specific cytoskeletal proteins in the activated platelets...
  29. ncbi Beta3 tyrosine phosphorylation in alphaIIbbeta3 (platelet membrane GP IIb-IIIa) outside-in integrin signaling
    D R Phillips
    COR Therapeutics, Inc, South San Francisco, CA 94080, USA
    Thromb Haemost 86:246-58. 2001
    ..Taken together, the data suggest that the beta3 tyrosine phosphorylation signaling mechanism is important to alphaIIbbeta3 function and might be applicable to a wide variety of integrin-mediated events...
  30. ncbi Integrin alpha IIb beta 3-dependent calcium signals regulate platelet-fibrinogen interactions under flow. Involvement of phospholipase C gamma 2
    Isaac Goncalves
    Australian Centre for Blood Diseases, Department of Medicine, Monash University, Box Hill Hospital, Victoria 3128, Australia
    J Biol Chem 278:34812-22. 2003
    ..Furthermore, they establish an important cooperative signaling role for PLC gamma 2 and ADP in regulating platelet adhesion efficiency on fibrinogen...
  31. pmc Megakaryocytes derived from embryonic stem cells implicate CalDAG-GEFI in integrin signaling
    Koji Eto
    Departments of Cell Biology and Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 99:12819-24. 2002
    ..01). These results establish that ES cells are a ready source of mature megakaryocytes for integrin studies and other biological applications, and they implicate CalDAG-GEFI in inside-out signaling to alphaIIbbeta3...
  32. ncbi Molecular basis of CIB binding to the integrin alpha IIb cytoplasmic domain
    William T Barry
    Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina 27599, USA
    J Biol Chem 277:28877-83. 2002
    ..The identification of essential interacting regions within alpha(IIb) and CIB provides tools for further probing potential interrelated functions of these proteins...
  33. ncbi Functional and structural correlations of individual alphaIIbbeta3 molecules
    Rustem I Litvinov
    Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, 421 Curie Blvd, 1054 BRB II III, Philadelphia, PA 19104 6058, USA
    Blood 104:3979-85. 2004
    ..Further, they are consistent with the presence of a linked equilibrium between single inactive and single active alphaIIbbeta3 molecules and active alphaIIbbeta3 clusters...
  34. ncbi Calcium integrin-binding protein activates platelet integrin alpha IIbbeta 3
    Shigeru Tsuboi
    Glycobiology Program, Cancer Research Center, The Burnham Institute, La Jolla, California 92037, USA
    J Biol Chem 277:1919-23. 2002
    ..This suggests that CIB plays an important role in one of the pathways that modulate the affinity of alpha(IIb)beta(3) for its ligand...
  35. ncbi Guidelines for percutaneous coronary interventions. The Task Force for Percutaneous Coronary Interventions of the European Society of Cardiology
    Sigmund Silber
    Kardiologische Praxis und Praxisklinik, Munchen, Germany
    Eur Heart J 26:804-47. 2005
    ....
  36. ncbi Structural basis of integrin activation by talin
    Kate L Wegener
    Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, England, UK
    Cell 128:171-82. 2007
    ....
  37. pmc Kindlin-1 and -2 directly bind the C-terminal region of beta integrin cytoplasmic tails and exert integrin-specific activation effects
    David S Harburger
    Department of Pharmacology and Interdepartmental Program in Vascular Biology and Transplantation, Yale University School of Medicine, New Haven, Connecticut 06520, USA
    J Biol Chem 284:11485-97. 2009
    ..We suggest that kindlins are adaptor proteins that regulate integrin activation, that kindlin expression levels determine their effects, and that kindlins may exert integrin-specific effects...
  38. pmc Mechanisms and consequences of agonist-induced talin recruitment to platelet integrin alphaIIbbeta3
    Naohide Watanabe
    Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA
    J Cell Biol 181:1211-22. 2008
    ..Thus, talin recruitment to alphaIIbbeta3 by RIAM mediates agonist-induced alphaIIbbeta3 activation, with implications for hemostasis and thrombosis...
  39. ncbi GPVI and integrin alphaIIb beta3 signaling in platelets
    S P Watson
    Division of Medical Sciences, Centre for Cardiovascular Sciences, Institute of Biomedical Research, The Medical School, University of Birmingham, Birmingham, UK
    J Thromb Haemost 3:1752-62. 2005
    ..The significance of these signaling cascades in platelet adhesion and platelet aggregation at arterial rates of shear is discussed...
  40. ncbi ACC/AHA 2002 guideline update for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction--summary article: a report of the American College of Cardiology/American Heart Association task force on practice guideli
    Eugene Braunwald
    J Am Coll Cardiol 40:1366-74. 2002
  41. ncbi Targeting platelets in acute experimental stroke: impact of glycoprotein Ib, VI, and IIb/IIIa blockade on infarct size, functional outcome, and intracranial bleeding
    Christoph Kleinschnitz
    Department of Neurology, University of Wurzburg, Wurzburg, Germany
    Circulation 115:2323-30. 2007
    ..In the present study, we addressed the pathogenic role of GPIb, GPVI, and the aggregation receptor GPIIb/IIIa in experimental stroke in mice...
  42. ncbi Conformation-specific blockade of the integrin GPIIb/IIIa: a novel antiplatelet strategy that selectively targets activated platelets
    Meike Schwarz
    Department of Cardiology, University of Freiburg, Freiburg, Germany
    Circ Res 99:25-33. 2006
    ..In conclusion, activation-specific GPIIb/IIIa blockade via human single-chain antibodies represents a promising novel strategy for antiplatelet therapy...
  43. ncbi Targeting ligand-induced binding sites on GPIIb/IIIa via single-chain antibody allows effective anticoagulation without bleeding time prolongation
    Patrick Stoll
    Centre for Thrombosis and Myocardial Infarction, Baker Heart Research Institute, PO Box 6492 St Kilda Road Central, Melbourne, Victoria 8008, Australia
    Arterioscler Thromb Vasc Biol 27:1206-12. 2007
    ..We investigate whether targeting of anticoagulants to activated platelets provides a means to overcome this association of potency and bleeding...
  44. ncbi Very early cardiac magnetic resonance imaging for quantification of myocardial tissue perfusion in patients receiving tirofiban before percutaneous coronary intervention for ST-elevation myocardial infarction
    Henning Steen
    Department of Medicine, Division of Cardiology, Johns Hopkins Medical Institutions, Baltimore, MD, USA
    Am Heart J 149:564. 2005
    ..Magnetic resonance imaging is a novel noninvasive method providing complementary information on myocardial blood flow and cardiac function...
  45. ncbi Early versus delayed, provisional eptifibatide in acute coronary syndromes
    Robert P Giugliano
    TIMI Thrombolysis in Myocardial Infarction Study Group, Brigham and Women s Hospital, Boston, MA 02115, USA
    N Engl J Med 360:2176-90. 2009
    ..Glycoprotein IIb/IIIa inhibitors are indicated in patients with acute coronary syndromes who are undergoing an invasive procedure. The optimal timing of the initiation of such therapy is unknown...
  46. ncbi Clopidogrel loading with eptifibatide to arrest the reactivity of platelets: results of the Clopidogrel Loading With Eptifibatide to Arrest the Reactivity of Platelets (CLEAR PLATELETS) study
    Paul A Gurbel
    Sinai Center for Thrombosis Research, Hoffberger Bldg, Suite 56, 2401 W Belvedere Ave, Baltimore, MD 21215, USA
    Circulation 111:1153-9. 2005
    ..Moreover, limited information is available on the antiplatelet pharmacodynamics of a 300-mg versus a 600-mg clopidogrel loading dose, and the comparative effect of eptifibatide with these regimens is unknown...
  47. ncbi A critical role for phospholipase Cgamma2 in alphaIIbbeta3-mediated platelet spreading
    Peter Wonerow
    Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, United Kingdom
    J Biol Chem 278:37520-9. 2003
    ..Therefore, PLCgamma2 plays not only a crucial role in activation of alphaIIbbeta3 by collagen receptors but also in alphaIIbbeta3-mediated responses...
  48. ncbi Effect of glycoprotein IIb/IIIa receptor blocker abciximab on outcome in patients with acute coronary syndromes without early coronary revascularisation: the GUSTO IV-ACS randomised trial
    M L Simoons
    Thoraxcenter, Room H 560, University Hospital Rotterdam, 3000 CA, Rotterdam, Netherlands
    Lancet 357:1915-24. 2001
    ..We did a randomised, multicentre trial to study the effect of the glycoprotein IIb/IIIa blocker abciximab on patients with acute coronary syndromes who were not undergoing early revascularisation...
  49. ncbi Effects of abciximab pretreatment in patients with acute myocardial infarction undergoing primary angioplasty
    Simona Zorman
    Center for Intensive Internal Medicine, Ljubljana, Slovenia
    Am J Cardiol 90:533-6. 2002
  50. ncbi Activation of integrin alphaIIbbeta3 by modulation of transmembrane helix associations
    Renhao Li
    Department of Biochemistry and Biophysics, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
    Science 300:795-8. 2003
    ..These results suggest that homomeric associations involving transmembrane domains provide a driving force for integrin activation. They also suggest a structural basis for the coincidence of integrin activation and clustering...
  51. pmc Comparative antiplatelet effects of aspirin, vapiprost and GR144053, a GPIIb/IIIa antagonist, with a special reference to the role of platelet microaggregates
    H Matsuno
    Department of Pharmacology, Gifu University School of Medicine, Japan
    Br J Pharmacol 127:1129-34. 1999
    ..This further indicates the importance of small aggregates as triggers of thrombosis and shows that prevention of their formation may result in improved vascular patency after thrombotic insult...
  52. pmc The structure of the integrin alphaIIbbeta3 transmembrane complex explains integrin transmembrane signalling
    Tong Lay Lau
    Department of Biochemistry and Molecular Biology, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
    EMBO J 28:1351-61. 2009
    ..The structurally unique, highly conserved integrin alphaIIbbeta3 TM complex rationalizes bi-directional signalling and represents the first structure of a heterodimeric TM receptor complex...
  53. ncbi Contribution of distinct adhesive interactions to platelet aggregation in flowing blood
    Z M Ruggeri
    Roon Research Center for Arteriosclerosis and Thrombosis, The Division of Experimental Hemostasis and Thrombosis, The Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, CA 92037, USA
    Blood 94:172-8. 1999
    ..The specific function of distinct adhesion pathways in response to changing hemodynamic conditions helps to explain hemostatic and thrombotic processes...
  54. ncbi Abciximab as adjunctive therapy to reperfusion in acute ST-segment elevation myocardial infarction: a meta-analysis of randomized trials
    Giuseppe De Luca
    Isala Klinieken, Hospital De Weezenlanden, Zwolle, The Netherlands
    JAMA 293:1759-65. 2005
    ..The benefits of abciximab in patients with ST-segment elevation myocardial infarction (STEMI) are still a matter of debate...
  55. ncbi Influence of concurrent renal dysfunction on outcomes of patients with acute coronary syndromes and implications of the use of glycoprotein IIb/IIIa inhibitors
    Rosario V Freeman
    Division of Cardiology, University of Washington, Seattle, Washington 98195, USA
    J Am Coll Cardiol 41:718-24. 2003
    ..The purpose of this study was to examine the in-hospital outcome and influence of glycoprotein (GP) IIb/IIIa antagonists on patients with acute coronary syndromes (ACS) across a range of renal function...
  56. ncbi Increased mortality with oral platelet glycoprotein IIb/IIIa antagonists: a meta-analysis of phase III multicenter randomized trials
    D P Chew
    Department of Cardiology, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    Circulation 103:201-6. 2001
    ..These findings suggest the potential for a direct toxic effect with these agents and argue against a prothrombotic mechanism. Further investigation to elucidate the cause of this increased fatality risk is warranted...
  57. pmc Talin is required for integrin-mediated platelet function in hemostasis and thrombosis
    Brian G Petrich
    Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA
    J Exp Med 204:3103-11. 2007
    ..These data establish that platelet talin plays a crucial role in hemostasis and provide the first proof that talin is required for the activation and function of mammalian alpha2beta1 and alphaIIbbeta3 integrins in vivo...
  58. ncbi Detection of integrin alpha IIbbeta 3 clustering in living cells
    Charito Buensuceso
    Departments of Cell Biology and Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, USA
    J Biol Chem 278:15217-24. 2003
    ..These studies in living cells establish that alpha(IIb)beta(3) clustering is modulated by fibrinogen and actin dynamics. More broadly, they should facilitate investigations of the mechanisms and consequences of integrin clustering...
  59. ncbi Achieved platelet aggregation inhibition after different antiplatelet regimens during percutaneous coronary intervention for ST-segment elevation myocardial infarction
    Nicolette M S K J Ernst
    Isala Klinieken, Location Weezenlanden, Department of Cardiology, Zwolle, The Netherlands
    J Am Coll Cardiol 44:1187-93. 2004
    ..To evaluate the extent of platelet aggregation inhibition in patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI), treated with different antiplatelet agents and dosages...
  60. ncbi Effect of glycoprotein IIb/IIIa receptor blockade with abciximab on clinical and angiographic restenosis rate after the placement of coronary stents following acute myocardial infarction
    F J Neumann
    Deutsches Herzzentrum und 1 Medizinische Klinik der Technischen Universität München, Munich, Germany
    J Am Coll Cardiol 35:915-21. 2000
    ..We also intended to assess the impact of abciximab on clinical outcome in this setting...
  61. ncbi 7E3 monoclonal antibody directed against the platelet glycoprotein IIb/IIIa cross-reacts with the leukocyte integrin Mac-1 and blocks adhesion to fibrinogen and ICAM-1
    D I Simon
    Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA, USA
    Arterioscler Thromb Vasc Biol 17:528-35. 1997
    ....
  62. ncbi Benefit of abciximab in patients with refractory unstable angina in relation to serum troponin T levels. c7E3 Fab Antiplatelet Therapy in Unstable Refractory Angina (CAPTURE) Study Investigators
    C W Hamm
    Department of Cardiology, University Hospital Eppendorf, Hamburg, Germany
    N Engl J Med 340:1623-9. 1999
    ..We investigated whether serum troponin T levels identify patients most likely to benefit from therapy with this drug...
  63. ncbi Platelet glycoprotein IIb/IIIa inhibition in acute coronary syndromes. Gradient of benefit related to the revascularization strategy
    M Roffi
    Department of Cardiovascular Medicine, The Cleveland Clinic Foundation, Cleveland, OH 441995, USA
    Eur Heart J 23:1441-8. 2002
    ..To assess the efficacy of platelet glycoprotein IIb/IIIa inhibitors in patients with acute coronary syndromes primarily medically managed...
  64. pmc Vav family proteins are required for optimal regulation of PLCgamma2 by integrin alphaIIbbeta3
    Andrew C Pearce
    Centre for Cardiovascular Sciences, Institute of Biomedical Research, Division of Medical Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK
    Biochem J 401:753-61. 2007
    ..These results demonstrate that Vav1 and Vav3 are required for optimal spreading and regulation of PLCgamma2 by integrin alphaIIbbeta3, but that their requirement is by-passed upon G-protein receptor activation...
  65. ncbi Early glycoprotein IIb/IIIa inhibitor use for non-ST-segment elevation acute coronary syndrome: patient selection and associated treatment patterns
    James W Hoekstra
    Department of Emergency Medicine, Wake Forest University Health Sciences, Medical Center Boulevard, Winston Salem, NC 27157, USA
    Acad Emerg Med 12:431-8. 2005
    ....
  66. pmc Proximal, selective, and dynamic interactions between integrin alphaIIbbeta3 and protein tyrosine kinases in living cells
    Maddalena de Virgilio
    Department of Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Rd, VB 5, La Jolla, CA 92037, USA
    J Cell Biol 165:305-11. 2004
    ..Thus, alphaIIbbeta3 interacts proximally, if not directly, with tyrosine kinases in a coordinated, selective, and dynamic manner during sequential phases of alphaIIbbeta3 signaling to the actin cytoskeleton...
  67. ncbi Disabled-2 is a novel alphaIIb-integrin-binding protein that negatively regulates platelet-fibrinogen interactions and platelet aggregation
    Chien Ling Huang
    Graduate Institute of Basic Medical Sciences, Chang Gung University, Taoyuan 333, Taiwan, Republic of China
    J Cell Sci 119:4420-30. 2006
    ..These findings demonstrate for the first time that DAB2 is an alphaIIb-integrin-binding protein that plays a novel role in the control of platelet-fibrinogen interactions and platelet aggregation...
  68. pmc Intercellular calcium communication regulates platelet aggregation and thrombus growth
    Warwick S Nesbitt
    Australian Centre for Blood Diseases, Department of Medicine, Monash University, Box Hill Hospital, Victoria 3128, Australia
    J Cell Biol 160:1151-61. 2003
    ..Furthermore, we demonstrate that the efficiency by which calcium signals are propagated within platelet aggregates plays an important role in dictating the rate and extent of thrombus growth...
  69. ncbi Eptifibatide provides additional platelet inhibition in non-ST-elevation myocardial infarction patients already treated with aspirin and clopidogrel. Results of the platelet activity extinction in non-Q-wave myocardial infarction with aspirin, clopidogrel
    Miles Dalby
    Institut de Cardiologie, Pitie Salpetriere University Hospital, Paris, France
    J Am Coll Cardiol 43:162-8. 2004
    ..The present study hypothesis was that eptifibatide offered further antiplatelet efficacy above clopidogrel in non-ST-elevation myocardial infarction (NSTEMI) patients before an expeditive coronary intervention...
  70. ncbi Platelet-collagen interaction: is GPVI the central receptor?
    Bernhard Nieswandt
    Department of Vascular Biology, Rudolf Virchow Center for Experimental Biomedicine Versbacher, Wurzburg, Germany
    Blood 102:449-61. 2003
    ..This review discusses these recent developments and proposes possible mechanisms for how GPVI acts in concert with other receptors and signaling pathways to initiate hemostasis and arterial thrombosis...
  71. ncbi Protein phosphatase 1 associates with the integrin alphaIIb subunit and regulates signaling
    K Vinod Vijayan
    Department of Medicine, Baylor College of Medicine, Houston, Texas 77030, USA
    J Biol Chem 279:33039-42. 2004
    ..These studies reveal a previously unrecognized role for integrins whereby the alpha subunit cytoplasmic tail localizes the machinery for initiating and temporally maintaining the regulatory signaling activity of a phosphatase...
  72. ncbi Abciximab in patients with acute coronary syndromes undergoing percutaneous coronary intervention after clopidogrel pretreatment: the ISAR-REACT 2 randomized trial
    Adnan Kastrati
    Deutsches Herzzentrum, Technische Universitat, Munich, Germany
    JAMA 295:1531-8. 2006
    ....
  73. ncbi Scientific and therapeutic advances in antiplatelet therapy
    Deepak L Bhatt
    Cleveland Clinic Foundation, Department of Cardiovascular Medicine Desk F25, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA
    Nat Rev Drug Discov 2:15-28. 2003
    ..New insights at the cellular and genomic levels will probably generate novel drugs to inhibit platelet function more effectively and safely than previously possible...
  74. ncbi A stimulatory role for cGMP-dependent protein kinase in platelet activation
    Zhenyu Li
    Department of Pharmacology, College of Medicine, University of Illinois, 835 South Wolcott Avenue, Chicago, IL 60612, USA
    Cell 112:77-86. 2003
    ..The cGMP-stimulated platelet responses are biphasic, consisting of an initial transient stimulatory response that promotes platelet aggregation and a subsequent inhibitory response that limits the size of thrombi...
  75. ncbi Tec regulates platelet activation by GPVI in the absence of Btk
    Ben T Atkinson
    Department of Pharmacology, University of Oxford, Mansfield Rd, Oxford, OX1 3QT, United Kingdom
    Blood 102:3592-9. 2003
    ..These results demonstrate an essential requirement for Tec and Btk in platelet activation by GPVI and reveal a functional role for Tec in the regulation of PLC gamma 2 in the absence of Btk...
  76. ncbi Randomized clinical trial of abciximab in diabetic patients undergoing elective percutaneous coronary interventions after treatment with a high loading dose of clopidogrel
    Julinda Mehilli
    Deutsches Herzzentrum, Lazarettstrasse 36, 80636 Munich, Germany
    Circulation 110:3627-35. 2004
    ....
  77. ncbi Integrin-dependent interaction of lipid rafts with the actin cytoskeleton in activated human platelets
    Stéphane Bodin
    INSERM U 563, Centre de Physiopathologie de Toulouse Purpan, Department of Oncogenesis and Signaling in Haematopoietic Cells, IFR30, Hopital Purpan, 31059 Toulouse, France
    J Cell Sci 118:759-69. 2005
    ..We propose that rafts participate in the organization of membrane-cytoskeleton interactions where alphaIIbbeta3-mediated tension forces apply during the late phase of platelet activation...
  78. ncbi Randomized COMparison of platelet inhibition with abciximab, tiRofiban and eptifibatide during percutaneous coronary intervention in acute coronary syndromes: the COMPARE trial. Comparison Of Measurements of Platelet aggregation with Aggrastat, Reopro, an
    Wayne B Batchelor
    Tallahassee Heart and Vascular Institute, Tallahassee Memorial Healthcare, Tallahassee, Fla 32308, USA
    Circulation 106:1470-6. 2002
    ..The relative anti-aggregatory effects of currently prescribed platelet glycoprotein IIb/IIIa receptor antagonists during and after percutaneous coronary intervention for acute coronary syndromes have not been established...
  79. ncbi Calcium-and integrin-binding protein regulates focal adhesion kinase activity during platelet spreading on immobilized fibrinogen
    Meghna U Naik
    Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA
    Blood 102:3629-36. 2003
    ..Taken together, our results suggest that CIB regulates platelet spreading through the regulation of FAK activation...
  80. ncbi Electron tomography reveals diverse conformations of integrin alphaIIbbeta3 in the active state
    Kenji Iwasaki
    International Institute for Advanced Research, Matsushita Electric Industrial Co, Ltd, 3 4 Hikaridai, Seika, Soraku, Kyoto 619 02
    J Struct Biol 150:259-67. 2005
    ..Our results demonstrate that electron tomography can be used to classify complexes with a flexible structure such as integrins...
  81. ncbi Eptifibatide and 7E3, but not tirofiban, inhibit alpha(v)beta(3) integrin-mediated binding of smooth muscle cells to thrombospondin and prothrombin
    M Lele
    Program in Molecular Cardiology, University of North Carolina, Chapel Hill, NC 27599-7075, USA
    Circulation 104:582-7. 2001
    ..CONCLUSIONS: Eptifibatide and 7E3, but not tirofiban, specifically inhibit alpha(v)beta(3)-mediated binding of human smooth muscle and endothelial cells...
  82. ncbi Variable protection of beta 3-integrin--deficient mice from thrombosis initiated by different mechanisms
    S S Smyth
    Department of Medicine, Mount Sinai School of Medicine, New York, NY, USA
    Blood 98:1055-62. 2001
    ..These results suggest that though alpha IIb beta 3 plays a dominant role in large-vessel thrombosis, it plays a variable role in systemic intravascular thrombosis. (Blood. 2001;98:1055-1062)..
  83. pmc Binding of a fibrinogen mimetic stabilizes integrin alphaIIbbeta3's open conformation
    R R Hantgan
    Department of Biochemistry, Wake Forest University School of Medicine, Winston Salem, North Carolina 27157, USA
    Protein Sci 10:1614-26. 2001
    ..By showing how eptifibatide and RGD peptides, ligands with distinct binding sites, each affects alphaIIbbeta3's conformation, our findings provide new mechanistic insights into ligand-linked integrin activation, clustering and signaling...
  84. ncbi Platelet glycoprotein IIb/IIIa inhibition with coronary stenting for acute myocardial infarction
    G Montalescot
    Division of Cardiology, Pitie Salpetriere Hospital, Paris, France
    N Engl J Med 344:1895-903. 2001
    ....
  85. ncbi Comparison of two platelet glycoprotein IIb/IIIa inhibitors, tirofiban and abciximab, for the prevention of ischemic events with percutaneous coronary revascularization
    E J Topol
    Department of Cardiology, Cleveland Clinic Foundation, OH 44195, USA
    N Engl J Med 344:1888-94. 2001
    ..We assessed whether there are differences in safety or efficacy between two such inhibitors, tirofiban and abciximab...
  86. ncbi Outcomes with the use of glycoprotein IIb/IIIa inhibitors in non-ST-segment elevation acute coronary syndromes
    O H Dabbous
    Center for Outcomes Research, University of Massachusetts Medical School, 365 Plantation Street, Suite 185, Worcester, MA 01605, USA
    Heart 94:159-65. 2008
    ....
  87. ncbi Multiple ways to switch platelet integrins on and off
    J M E M Cosemans
    Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands
    J Thromb Haemost 6:1253-61. 2008
    ..Back-shifting of activated integrins towards their resting state may be a novel goal of antithrombotic medication...
  88. pmc Sequential activation of p38 and ERK pathways by cGMP-dependent protein kinase leading to activation of the platelet integrin alphaIIb beta3
    Zhenyu Li
    Department of Pharmacology, University of Illinois College of Medicine, Chicago, IL 60612, USA
    Blood 107:965-72. 2006
    ..Thus, p38 plays an important role in mediating PKG-dependent activation of ERK. These data delineate a novel signaling pathway in which platelet agonists sequentially activate PKG, p38, and ERK pathways leading to integrin activation...
  89. pmc Protein phosphatase 2A negatively regulates integrin alpha(IIb)beta(3) signaling
    Francisca C Gushiken
    Department of Medicine, Baylor College of Medicine, Houston, Texas 77030, USA
    J Biol Chem 283:12862-9. 2008
    ..These studies demonstrate that PP2Ac (alpha) can negatively regulate integrin alpha(IIb)beta(3) signaling by suppressing the ERK1/2 signaling pathway...
  90. ncbi Identification of shc as the primary protein binding to the tyrosine-phosphorylated beta 3 subunit of alpha IIbbeta 3 during outside-in integrin platelet signaling
    K J Cowan
    COR Therapeutics, Inc, South San Francisco, California 94080, USA
    J Biol Chem 275:36423-9. 2000
    ..Thus, Shc is the primary downstream signaling partner of beta(3) in its tyrosine phosphorylation outside-in signaling pathway...
  91. ncbi Randomized early versus late abciximab in acute myocardial infarction treated with primary coronary intervention (RELAx-AMI Trial)
    Mauro Maioli
    Division of Cardiology, Misericordia e Dolce Hospital, Prato, Italy
    J Am Coll Cardiol 49:1517-24. 2007
    ..This prospective randomized trial evaluates the impact of early abciximab administration on angiographic and left ventricular function parameters...
  92. pmc The antithrombotic potential of selective blockade of talin-dependent integrin alpha IIb beta 3 (platelet GPIIb-IIIa) activation
    Brian G Petrich
    Department of Medicine, UCSD School of Medicine, La Jolla, California 92093 0726, USA
    J Clin Invest 117:2250-9. 2007
    ..Furthermore, they suggest that modulation of beta(3) integrin-talin interactions may provide an attractive target for antithrombotics and result in a reduced risk of pathological bleeding...
  93. ncbi Inhibition of platelet aggregation with eptifibatide, bivalirudin, and heparin in patients undergoing percutaneous coronary intervention receiving clopidogrel pretreatment (The PharmacoDynamic Evaluation of Angiomax, Clopidogrel with or without INtegrilin
    Jorge F Saucedo
    University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, USA
    Am J Cardiol 95:1453-6. 2005
    ....
  94. ncbi Management and outcome of patients with established coronary artery disease: the Euro Heart Survey on coronary revascularization
    M J Lenzen
    Department of Cardiology, Erasmus MC, Thoraxcenter, Rotterdam, The Netherlands
    Eur Heart J 26:1169-79. 2005
    ..The current survey focuses on the invasive diagnosis and treatment of patients with established coronary artery disease (CAD)...
  95. ncbi Relationships between Rap1b, affinity modulation of integrin alpha IIbbeta 3, and the actin cytoskeleton
    Alessandra Bertoni
    Department of Cell Biology, The Scripps Research Institute, La Jolla, California 92037, USA
    J Biol Chem 277:25715-21. 2002
    ..These studies establish that Rap1b can augment agonist-induced ligand binding to alpha(IIb)beta(3) through effects on integrin affinity, possibly by modulating alpha(IIb)beta(3) interactions with the actin cytoskeleton...
  96. ncbi Correlates of bleeding events among moderate- to high-risk patients undergoing percutaneous coronary intervention and treated with eptifibatide: observations from the PROTECT-TIMI-30 trial
    Ajay J Kirtane
    Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, USA
    J Am Coll Cardiol 47:2374-9. 2006
    ..We aimed to identify correlates of Thrombolysis In Mycocardial Infarction (TIMI) major/minor bleeding among eptifibatide-treated patients undergoing percutaneous coronary intervention (PCI)...
  97. pmc Coordinate interactions of Csk, Src, and Syk kinases with [alpha]IIb[beta]3 initiate integrin signaling to the cytoskeleton
    Achim Obergfell
    Division of Vascular Biology, Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
    J Cell Biol 157:265-75. 2002
    ..These studies establish that platelet spreading on fibrinogen requires sequential activation of Src and Syk in proximity to alphaIIbbeta3, thus providing a paradigm for initiation of integrin signaling to the actin cytoskeleton...
  98. ncbi Comparison of angioplasty with stenting, with or without abciximab, in acute myocardial infarction
    Gregg W Stone
    Cardiovascular Research Foundation and Lenox Hill Heart and Vascular Institute, New York, NY 10022, USA
    N Engl J Med 346:957-66. 2002
    ..When used in combination with PTCA, coronary stenting and platelet glycoprotein IIb/IIIa inhibitors may further improve outcomes...
  99. ncbi Platelet glycoprotein IIb/IIIa inhibitors in acute coronary syndromes: a meta-analysis of all major randomised clinical trials
    Eric Boersma
    University Hospital Rotterdam, Rotterdam, The Netherlands
    Lancet 359:189-98. 2002
    ....
  100. ncbi Platelet integrin alpha(IIb)beta(3): activation mechanisms
    Y Q Ma
    Department of Molecular Cardiology, Joseph J Jacobs Center for Thrombosis and Vascular Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA
    J Thromb Haemost 5:1345-52. 2007
    ..Among them, talin appears to be a critical trigger of alpha(IIb)beta(3) activation, but other binding partners, which function as activators or suppressors, are likely to act as co-regulators of integrin activation...

Research Grants67

  1. ROLE OF FACTOR XIII BINDING TO THE HEMOSTATIC PLUG
    Charles Greenberg; Fiscal Year: 1993
    ..Results from these studies may have direct application to the development of diagnostic and therapeutic agents which could benefit several thrombotic disorders including myocardial infraction, stroke and pulmonary embolization...
  2. THE ROLE OF CONTRACTILE PROTEINS IN PLATELETS
    ELENA PUSZKIN; Fiscal Year: 1990
    ..These studies may clarify the complex interactions that occur between the membrane of platelets with the internal cytoskeleton that are active in supporting platelet function during aggregation and/or thrombus formation...
  3. INTEGRIN-CYTOSKELETAL INTERACTIONS IN PLATELETS
    Keith Burridge; Fiscal Year: 1992
    ..If kinases are discovered, we will examine their substrates to determine whether phosphorylation modifies their interaction with integrins or cytoskeletal proteins...
  4. MEGAKARYOCYTIC REGULATION OF THE ALPHA-2 INTEGRIN GENE
    MARY ZUTTER; Fiscal Year: 2000
    ....
  5. INTERACTION OF OSTEOPONTIN WITH ADHESION RECEPTORS
    JOEL BENNETT; Fiscal Year: 2002
    ..Our results suggest that it may be possible to inhibit the formation of platelet thrombi in arteries involved by atherosclerosis by preventing the interaction of platelet alphavbeta3 with osteopontin. ..
  6. Nanoparticle targeting of cathepsin-L inhibitor and doxorubicin in breast cancer
    Shaker Mousa; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  7. POSTDOCTORAL HEMATOLOGY RESEARCH TRAINING
    George Dale; Fiscal Year: 2003
    ..Francis Fdt. (OUHSC). All members of the faculty work closely together under Specialized Center of Research (SCOR) and Program Project (PP)...
  8. Genetic Predictors of Outcome in Acute MI
    Marc Sabatine; Fiscal Year: 2005
    ..Genomic control will be employed to detect and control for population stratification. Interaction terms will be incorporated into regression models to explore gene-environment and pharmacogenomic interactions. ..
  9. COAT-Platelets
    George Dale; Fiscal Year: 2005
    ..abstract_text> ..
  10. Modulation of integrin function by cytoplasmic signals
    Ulhas Naik; Fiscal Year: 2007
    ..Further, characterization of CIB and its interactions with integrin alphaIIb-beta3 and Plk3 may help in delineating the mechanisms by which cytoplasmic signals modulate integrin function. ..
  11. ESCAPE Mechanistic Substudies
    Robert Califf; Fiscal Year: 2003
    ..Catecholamines are also being collected at baseline and 3 months. In addition, the ESCAPE investigators are all ready capturing detailed demographic, clinical, and physiological information as part of the protocol for the primary study. ..
  12. Role of JAM Family in Angiogenesis
    Ulhas P Naik; Fiscal Year: 2010
    ..Further, elucidation of the role of JAM-A in endothelial cell proliferation and migration leading to angiogenesis will open up a mew line of investigation that is important in tumerigenesis and vascular biology. ..
  13. Mechanisms of Pro-Thrombosis in Diabetes Mellitus
    David Schneider; Fiscal Year: 2003
    ..Further, these results will define the importance of prothrombotic potential in diabetic subjects while potentially identifying new therapeutic targets in patients with diabetes and other insulin resistant states. ..
  14. Radiolabeled Peptides for Imaging Tumor Angiogenesis
    LINDA KNIGHT; Fiscal Year: 2004
    ..A future benefit of this approach is the potential for targeted radiotherapy of tumors by labeling the same disintegrin with a therapeutic radionuclide. ..
  15. LEUKOCYTE INTEGRIN ALPHA M BETA 2
    Edward Plow; Fiscal Year: 2004
    ....
  16. Initiation and Regulation of Platelet Thrombus Formation
    ZAVERIO RUGGERI; Fiscal Year: 2004
    ..The results of the proposed studies will have an impact on public health by providing novel mechanistic information on processes that are central to normal hemostasis and pathological arterial thrombosis. ..
  17. Thrombospondins and Atherothrombosis
    Edward Plow; Fiscal Year: 2004
    ..Together, these studies should provide a rigorous test of the hypothesis and extend our knowledge of the roles of the TSPs in cardiovascular biology. ..
  18. Platelet interactions with vessel wall components
    ZAVERIO RUGGERI; Fiscal Year: 2005
    ..These findings will provide a better definition and characterization of several potential targets for antithrombotic intervention that may yield new treatments for patients at risk of cardiovascular and cerebrovascular events. ..
  19. Mechanisms of Thrombus Instability
    ZAVERIO RUGGERI; Fiscal Year: 2007
    ..These studies will provide novel insights into the unexpected role of leptin in platelet function, and in the formation and stability of thrombi. ..
  20. 2004 Hemostasis Gordon Research Conference
    Edward Plow; Fiscal Year: 2004
    ..The Hemostasis Gordon Conference has been a highly successful and enjoyable meeting, frequently identified as the best meeting attended by participants; and we believe that the current program has the potential to extend this tradition. ..
  21. Re-Engineering the Clinical Research Enterprise
    Robert Harrington; Fiscal Year: 2004
    ....
  22. Actin assembly in platelets & megakaryoctyes
    Charles Abrams; Fiscal Year: 2008
    ..In the second Aim, we will formally address how PIP2 drives reorganization of platelet actin using a combination of biochemistry, murine genetics, and ex vivo platelet adhesion models. ..
  23. THE STRUCTURE AND FUNCTION OF PLATELET GPIIB-IIIA
    Edward Plow; Fiscal Year: 2003
    ..At the same time, these studies may have direct bearing on the use and future development of the GPIIb-IIIa blockers as antithrombotic agents. ..
  24. Role of von Willebrand Factor in Platelet Thrombus Formation
    Zaverio M Ruggeri; Fiscal Year: 2010
    ..Understanding these different functions requires addressing structural details as well as verification of concepts in intravidal models. This will lead to a better diagnosis and treatment for cardio- and cerebro-vascular diseases. ..
  25. BIACORE 3000
    Lisa Jennings; Fiscal Year: 2001
    ..We are requesting a BIACORE 3000 to enhance our research activity and productivity and to assist us in accomplishing the goals of our funded NIH grants...
  26. AUTOIMMUNE THROMBOCYTOPENIA
    Robert McMillan; Fiscal Year: 2002
    ..Results of these studies will be correlated with the patients' clinical course and thrombopoietin levels. In addition, the effect of immune thrombocytopenia on the patients' quality of life will be studied. ..
  27. MECHANISMS OF HORMONE THERAPY IN POSTMENOPAUSAL WOMEN
    L Newby; Fiscal Year: 2003
    ....
  28. Structure and function of platelet membrane glycoproteins
    ZAVERIO RUGGERI; Fiscal Year: 2008
    ..abstract_text> ..
  29. RADIOLABLED PEPTIDES FOR IMAGING THROMBI AND EMBOLI
    LINDA KNIGHT; Fiscal Year: 2003
    ..abstract_text> ..
  30. Roles of the WASP N-terminus in hematopoietic cells
    Shigeru Tsuboi; Fiscal Year: 2006
    ..in hematopoietic cells will provide important information about critical biological processes such as cell migration, and it should facilitate the development of potential therapeutic agent to treat XLT and WAS ..
  31. Mesenchymal Stem Cells for Myocardial Infarction
    Robert Kloner; Fiscal Year: 2006
    ..abstract_text> ..
  32. Safer Antithrombotic Therapy for Elderly ACS Patients
    Eric Peterson; Fiscal Year: 2006
    ..Finally, we will use established relations with professional societies and the VHA to widely disseminate our study's major findings. ..
  33. A Variant of Ileal Bile Acid Binding Protein in Colon Cancer
    Jeffrey Smith; Fiscal Year: 2006
    ..unreadable] [unreadable]..
  34. Therapeutic-Expression of a Platelet-Specific Integrin
    DAVID ALLEN WILCOX; Fiscal Year: 2010
    ..This study should lead to the development of safe and effective methods for human gene therapy for inherited platelet bleeding disorders and other diseases of hemostasis. ..
  35. Microvascular injury after Subarachnoid Hemorrhage
    Fatima A Sehba; Fiscal Year: 2010
    ....
  36. Ischemic Stroke Treatment with Microbubbles, a Novel Clot Lysis Therapeutic
    William C Culp; Fiscal Year: 2010
    ..Our proposed pilot study will determine which of these treatments is most successful, and future studies will further explore that treatment. (End of Abstract) ..
  37. Characterizing the Phenotype of Staphylococcal Biofilms
    Julia Ross; Fiscal Year: 2008
    ..Completion of these specific aims will provide a rational basis for the design of new therapeutic molecules. ..
  38. Pharmacogenetic Antiplatelet Strategies in CHD Patients
    Glen Cooke; Fiscal Year: 2007
    ..Such information will be paramount in the targeting of antiplatelet therapies and will be based on genomlc information (pharmacogenetics)...
  39. HEMORRHAGIC DISEASES
    RICHARD ASTER; Fiscal Year: 2008
    ..Relevance. Immune-mediated blood disorders are a major cause of morbidity and mortality. The proposed studies will lead to a better understanding of causation and improved diagnosed and treatment. ..
  40. Membrane Binding and Imaging Applications of Annexins
    Jonathan Tait; Fiscal Year: 2007
    ..Determine which mutant proteins have faster removal from the target site, thus allowing for repeated measurement of PS expression over short periods of time (up to one day). ..
  41. Targeting Metastatic Breast Cancer with Human Antibodies
    Brunhilde Felding Habermann; Fiscal Year: 2009
    ..Novel immunoconjugates containing small, highly toxic compounds will be tested for their effects on metastatic breast cancer. If successful, this work will contribute to an improvement of current anti-cancer treatment. ..
  42. Ischemia Reperfusion Injury in the Diabetic Heart
    Paul McDonagh; Fiscal Year: 2007
    ..The results will improve our understanding of the role of chronic and acute inflammation in I/R injury in the diabetic heart and suggest new, thoughtful approaches to treat this growing problem. [unreadable] [unreadable]..
  43. Defects in Mitochondria Impacting Primate Oocyte Quality
    DAVID RANDALL ARMANT; Fiscal Year: 2010
    ..Information gained in this study will also improve our understanding of the role of mitochondria in primate oocyte and embryo biology, and in the progressive loss of female reproductive capacity with age. ..
  44. Integrin Activation in Breast Cancer Metastasis
    Brunhilde Felding Habermann; Fiscal Year: 2006
    ....
  45. Apoptotic and non-apoptotic death responses to Shigella
    Beatrice Haimovich; Fiscal Year: 2003
    ..triggered by virulent Shigella linked to, and dependent on, the production of reactive oxygen intermediates by the infected cells? Aim 2: Is the response of human macrophages to Shigella dependent on the Shigella protein IpgBl? ..
  46. MECHANISM OF ACTIVATION OF PLATELET GPIIB AND GPIIIA
    Jeffrey Smith; Fiscal Year: 2001
    ..Binding studies will be performed between Ca2+ and purified conformers of dormant and active IIb-IIIa. Results from this analysis should determine which class of ion binding sites regulate activation of the integrin. ..
  47. COLLABORATIVE R01-CARDIAC GRAFTS-FUNCTIONAL ANALYSES
    Robert Kloner; Fiscal Year: 2003
    ....
  48. INTEGRIN CYTODOMAIN ANTI-THROMBOTICS
    David Phillips; Fiscal Year: 2002
    ..In the long term we will develop these novel inhibitors of alphaIIbbeta3 to offer improved therapy for the large population afflicted with ischemic cardiovascular diseases. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE ..
  49. ANGIOSTATIN--MOLECULAR MECHANISMS AND INTERACTIONS
    DAVID SANE; Fiscal Year: 2002
    ..These studies will lead to a better understanding of the mechanisms of angiogenesis inhibition by angiostatin. ..
  50. ALPHA V INTEGRINS IN BREAST CANCER
    Jeffrey Smith; Fiscal Year: 2002
    ..Results from these analyses will greatly augment the interpretation of results obtained from the experiments on tumor metastasis. ..
  51. DISINTEGRINS & METALLOPROTEINASES IN ORTHOPEDIC DISEASE
    Jeffrey Smith; Fiscal Year: 2002
    ..Homology-based PCR will be used to clone osteoclast ADAMs. Antibodies against these ADAMs will be used in attempts to block osteoclast differentiation. ..
  52. ETHANOL, SIGNAL TRANSDUCTION AND EMBRYONIC CELL SURVIVAL
    DAVID ARMANT; Fiscal Year: 2002
    ..The proposed experiments may identify signal transduction inhibitors or growth factors to ameliorate the downstream effects of ethanol in vitro, and suggest strategies for therapeutic intervention during pregnancy. ..
  53. ETIOLOGY OF STROKE IN CHILDREN WITH SICKLE CELL DISEASE
    Sherri Zimmerman; Fiscal Year: 2004
    ..Based on this fact-finding study, I will design a hypothesis-driven therapeutic clinical trial for children at highest risk of developing stroke. ..
  54. Lipid Testing /Treatment in Older MI Patients
    JoAnne Foody; Fiscal Year: 2005
    ..This work will ultimately improve care for the elderly patient with cardiovascular disease. ..
  55. CYCLOOXYGENASE-2 AND XENOBIOTICS IN VASCULAR INJURY
    Babette Weksler; Fiscal Year: 2005
    ..abstract_text> ..
  56. AMYLOD BETA-PEPTIDE SPECIFIC scFv ANTIBODIES
    Goar Gevorkian; Fiscal Year: 2005
    ..If successful, these molecules could be of interest for passive immunization in humans, may be after modification with substances that would increase their blood-brain barrier permeability. ..
  57. Molecular Characterization of a Human Dysfibrinogen
    VERONICA FLOOD; Fiscal Year: 2005
    ..This study will provide valuable information about the structural and functional behavior of this dysfibrinogen and will ultimately improve understanding of clot formation and the process of hemostasis. ..
  58. CELL SURFACE STRUCTURE AND TRANSFORMATIONS
    Richard Hynes; Fiscal Year: 2005
    ..Evaluation of the functions of cell adhesion proteins and the consequences of their misexpression in metastatic cells will lead to new leads for therapeutic interventions against metastasis. ..
  59. DYNAMIC PLATELET - STAPHYLOCOCCAL INTERACTIONS
    Julia Ross; Fiscal Year: 2004
    ..Completion of these specific aims will provide a rational basis for the design of new therapeutic molecules to block specific adhesion events, as well as identify the most important bacterial receptors to target in vaccine development. ..
  60. VASCULAR INTERACTION WITH AGE IN MYOCARDIAL INFARCTION
    Steven Schulman; Fiscal Year: 2004
    ..We anticipate that the study findings will suggest the use of new evaluation and therapeutic strategies, which will significantly decrease the age associated mortality and morbidity in post-infarction patients. ..
  61. Biologic Ventricular Assist Device
    Robert Kloner; Fiscal Year: 2004
    ..Identification and characterization of transplants will be carried out with PCR analysis of the Y chromosome (male cells into female host), detailed histologic analysis and immunostaining for muscle cell markers. ..
  62. Structure/Function Studies of the Integrin
    Thomas A Bunch; Fiscal Year: 2010
    ..We will pursue experiments that will address this hypothesis, potentially redefining the role of talin in integrin regulation. ..
  63. Novel On-line Education in Protection of Human Subjects
    Barry Coller; Fiscal Year: 2003
    ..Questionnaires for researchers and data queries of the educational system will be designed to conduct research describing the impact of the training program on trainees and investigators. ..
  64. STRUCTURE/FUNCTION ANALYSIS OF THE UROKINASE RECEPTOR
    Douglas Cines; Fiscal Year: 2002
    ..abstract_text> ..
  65. High Throughput Screen for Novel Inhibitors of Platelet Integrin alphaIIb-beta3
    Barry Coller; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  66. DEFENSIN AND THE PATHOGENESIS OF ATHEROSCLEROSIS
    Douglas Cines; Fiscal Year: 2002
    ..Finally, the interaction between endogenous defensin and endogenous Lp(a) will be examined in a novel transgenic mouse than overexpresses both human defensin and human Lp(a). ..
  67. Nuclear translocation of urokinase/nucleolin complexes
    Douglas Cines; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..