EDWARD FRANKLIN PLOW

Summary

Affiliation: Cleveland Clinic Foundation
Country: USA

Publications

  1. pmc Kindlin-3 enhances breast cancer progression and metastasis by activating Twist-mediated angiogenesis
    Khalid Sossey-Alaoui
    2Department of Molecular Cardiology, Cleveland Clinic Lerner Research Institute, 9500 Euclid Ave NB50, Cleveland, OH 44195, USA E F P
    FASEB J 28:2260-71. 2014
  2. 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
  3. pmc Migfilin and filamin as regulators of integrin activation in endothelial cells and neutrophils
    Mitali Das
    Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, United States of America
    PLoS ONE 6:e26355. 2011
  4. pmc The integrin co-activator Kindlin-3 is expressed and functional in a non-hematopoietic cell, the endothelial cell
    Katarzyna Bialkowska
    Department of Molecular Cardiology, Joseph J Jacobs Center for Thrombosis and Vascular Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA
    J Biol Chem 285:18640-9. 2010
  5. pmc Macrophage gene expression and foam cell formation are regulated by plasminogen
    Riku Das
    Department of Molecular Cardiology, Cleveland Clinic, Cleveland, OH 44195, USA
    Circulation 127:1209-18, e1-16. 2013
  6. pmc So many plasminogen receptors: why?
    Edward F Plow
    Department of Molecular Cardiology, Joseph J Jacobs Center for Thrombosis and Vascular Biology, Cleveland Clinic, Cleveland, OH 44195, USA
    J Biomed Biotechnol 2012:141806. 2012
  7. pmc miR-31 and its host gene lncRNA LOC554202 are regulated by promoter hypermethylation in triple-negative breast cancer
    Katarzyna Augoff
    Department of Molecular Cardiology, Cleveland Clinic, Cleveland, OH, USA
    Mol Cancer 11:5. 2012
  8. pmc Integrin alpha(M)beta(2)-mediated cell migration to fibrinogen and its recognition peptides
    C B Forsyth
    Joseph J. Jacobs Center for Thrombosis and Vascular Biology, and the Department of Molecular Cardiology, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    J Exp Med 193:1123-33. 2001
  9. ncbi request reprint AlphaIIbbeta3 and its antagonism at the new millennium
    E F Plow
    Department of Molecular Cardiology, Cleveland Clinic Foundation, OH 44195, USA
    Thromb Haemost 86:34-40. 2001
  10. ncbi request reprint The functions of plasminogen in cardiovascular disease
    Edward F Plow
    Department of Molecular Cardiology, Joseph J Jacobs Center for Thrombosis and Vascular Biology, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    Trends Cardiovasc Med 14:180-6. 2004

Research Grants

  1. LEUKOCYTE INTEGRIN ALPHA M BETA 2
    Edward Plow; Fiscal Year: 2003
  2. LEUKOCYTE INTEGRIN ALPHA M BETA 2
    Edward Plow; Fiscal Year: 2004
  3. CLASSICAL AND ALTERNATIVE PATHWAYS OF FIBRINOLYSIS
    Edward Plow; Fiscal Year: 2004
  4. Thrombospondins and Atherothrombosis
    Edward Plow; Fiscal Year: 2004
  5. 2004 Hemostasis Gordon Research Conference
    Edward Plow; Fiscal Year: 2004
  6. CLASSICAL AND ALTERNATIVE PATHWAYS OF FIBRINOLYSIS
    Edward Plow; Fiscal Year: 2005
  7. CLASSICAL AND ALTERNATIVE PATHWAYS OF FIBRINOLYSIS
    Edward Plow; Fiscal Year: 2006
  8. Training Program in Vascular Biology and Pathology
    Edward Plow; Fiscal Year: 2007
  9. CLASSICAL AND ALTERNATIVE PATHWAYS OF FIBRINOLYSIS
    Edward Plow; Fiscal Year: 2007
  10. Activation of the beta-3 integrins: Role of the kindlins
    Edward Plow; Fiscal Year: 2009

Collaborators

Detail Information

Publications75

  1. pmc Kindlin-3 enhances breast cancer progression and metastasis by activating Twist-mediated angiogenesis
    Khalid Sossey-Alaoui
    2Department of Molecular Cardiology, Cleveland Clinic Lerner Research Institute, 9500 Euclid Ave NB50, Cleveland, OH 44195, USA E F P
    FASEB J 28:2260-71. 2014
    ..Pluskota, E., Davuluri, G., Bialkowska, K., Das, M., Szpak, D., Lindner, D. J., Downs-Kelly, E., Thompson, C. L., Plow, E. F. Kindlin-3 enhances breast cancer progression and metastasis by activating Twist-mediated angiogenesis. ..
  2. 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...
  3. pmc Migfilin and filamin as regulators of integrin activation in endothelial cells and neutrophils
    Mitali Das
    Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, United States of America
    PLoS ONE 6:e26355. 2011
    ..Thus, filamin can act broadly as an inhibitor and migfilin is a promoter of integrin activation...
  4. pmc The integrin co-activator Kindlin-3 is expressed and functional in a non-hematopoietic cell, the endothelial cell
    Katarzyna Bialkowska
    Department of Molecular Cardiology, Joseph J Jacobs Center for Thrombosis and Vascular Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA
    J Biol Chem 285:18640-9. 2010
    ..Thus, the prevailing view that individual kindlins exert their functions in a cell type-specific manner must now be modified to consider distinct functions of the different family members within the same cell type...
  5. pmc Macrophage gene expression and foam cell formation are regulated by plasminogen
    Riku Das
    Department of Molecular Cardiology, Cleveland Clinic, Cleveland, OH 44195, USA
    Circulation 127:1209-18, e1-16. 2013
    ..Deciphering the molecular and cellular processes that govern macrophage foam cell formation is critical to understanding the basic mechanisms underlying atherosclerosis and other vascular pathologies...
  6. pmc So many plasminogen receptors: why?
    Edward F Plow
    Department of Molecular Cardiology, Joseph J Jacobs Center for Thrombosis and Vascular Biology, Cleveland Clinic, Cleveland, OH 44195, USA
    J Biomed Biotechnol 2012:141806. 2012
    ..Furthermore, several different plasminogen receptors can be used to support the same cellular response, such as inflammatory cell migration. Here, we discuss the perplexing issue: why are there so many different Plg-Rs?..
  7. pmc miR-31 and its host gene lncRNA LOC554202 are regulated by promoter hypermethylation in triple-negative breast cancer
    Katarzyna Augoff
    Department of Molecular Cardiology, Cleveland Clinic, Cleveland, OH, USA
    Mol Cancer 11:5. 2012
    ..The molecular mechanisms that lead to the loss of miR-31 and the activation of its pro-metastatic target genes during these specific steps of the invasion-metastasis cascade are however unknown...
  8. pmc Integrin alpha(M)beta(2)-mediated cell migration to fibrinogen and its recognition peptides
    C B Forsyth
    Joseph J. Jacobs Center for Thrombosis and Vascular Biology, and the Department of Molecular Cardiology, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    J Exp Med 193:1123-33. 2001
    ..Taken together, these data define specific molecular requirements for alpha(M)beta(2) to mediate cell migration to Fg derivatives and assign a novel proinflammatory activity to the P2 peptide...
  9. ncbi request reprint AlphaIIbbeta3 and its antagonism at the new millennium
    E F Plow
    Department of Molecular Cardiology, Cleveland Clinic Foundation, OH 44195, USA
    Thromb Haemost 86:34-40. 2001
    ..As illustrated by these two examples, there is still much to be learned about alphaIIbbeta3 if we are to fully appreciate its functions and its potential as a therapeutic target...
  10. ncbi request reprint The functions of plasminogen in cardiovascular disease
    Edward F Plow
    Department of Molecular Cardiology, Joseph J Jacobs Center for Thrombosis and Vascular Biology, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    Trends Cardiovasc Med 14:180-6. 2004
    ..Dissection of these mechanisms represents a future challenge toward understanding the roles of Plg in vivo...
  11. ncbi request reprint Vitronectin: back into the spotlight
    E F Plow
    Cleveland Clinic Foundation, Cleveland, OH 44195, USA
    J Thromb Haemost 3:873-4. 2005
  12. pmc Kindling the flame of integrin activation and function with kindlins
    Edward F Plow
    Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic, OH 44195, USA
    Curr Opin Hematol 16:323-8. 2009
    ..However, in-vivo data on the functions of the kindlins and their mechanisms of action have been lacking...
  13. ncbi request reprint Identification of the binding site for fibrinogen recognition peptide gamma 383-395 within the alpha(M)I-domain of integrin alpha(M)beta2
    V P Yakubenko
    Joseph J. Jacobs Center for Thrombosis and Vascular Biology and the Department of Molecular Cardiology, Lerner Research Institute, Cleveland, Ohio 44195, USA
    J Biol Chem 276:13995-4003. 2001
    ....
  14. ncbi request reprint Differential induction of gelatinase B (MMP-9) and gelatinase A (MMP-2) in T lymphocytes upon alpha(4)beta(1)-mediated adhesion to VCAM-1 and the CS-1 peptide of fibronectin
    V P Yakubenko
    Joseph J Jacobs Center for Thrombosis and Vascular Biology, Lerner Research Institute of The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    Exp Cell Res 260:73-84. 2000
    ....
  15. pmc Activation of alphaVbeta3 on vascular cells controls recognition of prothrombin
    T V Byzova
    Joseph J Jacobs Center for Thrombosis and Vascular Biology, Department of Molecular Cardiology, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    J Cell Biol 143:2081-92. 1998
    ..The capacity of alphaVbeta3 to interact with prothrombin may play a significant role in the maintenance of hemostasis; and, at a general level, ligand selection by alphaVbeta3 may be controlled by the activation state of this integrin...
  16. ncbi request reprint Activation of integrin alpha(V)beta(3) regulates cell adhesion and migration to bone sialoprotein
    T V Byzova
    Joseph J Jacobs Center for Thrombosis and Vascular Biology, Department of Molecular Cardiology, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA
    Exp Cell Res 254:299-308. 2000
    ..The constitutive activation of alpha(V)beta(3) on neoplastic cells may contribute to tumor growth and metastatic potential...
  17. ncbi request reprint The ligand recognition specificity of beta3 integrins
    K Suehiro
    Department of Molecular Cardiology, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    J Biol Chem 271:10365-71. 1996
    ....
  18. ncbi request reprint Selective inhibition of factor Xa during thrombolytic therapy markedly improves coronary artery patency in a canine model of coronary thrombosis
    F A Nicolini
    Department of Cardiology, Joseph J Jacobs Center for Thrombosis and Vascular Biology, Cleveland, Ohio, USA
    Blood Coagul Fibrinolysis 7:39-48. 1996
    ..These findings highlight the potential adverse effects of unchecked thrombin generation in the setting of thrombolytic therapy...
  19. ncbi request reprint Role of platelets in restenosis after percutaneous coronary revascularization
    H Le Breton
    Department of Cardiology, Cleveland Clinic Foundation, Ohio 44195 5066, USA
    J Am Coll Cardiol 28:1643-51. 1996
    ..Considerable further study is necessary to unravel the effects of platelets on the restenosis process...
  20. ncbi request reprint 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...
  21. ncbi request reprint Platelet GPIIb-IIIa blockers
    E J Topol
    Joseph J Jacobs Center for Thrombosis and Vascular Biology, Department of Cardiology, Cleveland Clinic Foundation, Ohio 44195, USA
    Lancet 353:227-31. 1999
    ..With attention to heparin dose the risk of bleeding is not a major concern with these agents. The GPIIb-IIIa blockers are taking the clinician and patient out of the era of aspirin monotherapy when platelet inhibition is required...
  22. ncbi request reprint A mechanism for modulation of cellular responses to VEGF: activation of the integrins
    T V Byzova
    Joseph J Jacobs Center for Thrombosis and Vascular Biology, Department of Molecular Cardiology, Cleveland Clinic Foundation, Ohio 44195, USA
    Mol Cell 6:851-60. 2000
    ..Thus, integrin activation provides a mechanism for VEGF to induce a broad spectrum of cellular responses...
  23. ncbi request reprint A discrete site modulates activation of I domains. Application to integrin alphaMbeta2
    L Zhang
    Joseph J Jacobs Center for Thrombosis and Vascular Biology, Department of Molecular Cardiology, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    J Biol Chem 271:29953-7. 1996
    ..In support of this hypothesis, several naturally occurring mutations that activate von Willebrand factor map to the same loops of its I(A) domain...
  24. ncbi request reprint Single nucleotide polymorphisms in multiple novel thrombospondin genes may be associated with familial premature myocardial infarction
    E J Topol
    Cleveland Clinic Foundation, Cleveland, Ohio, USA
    Circulation 104:2641-4. 2001
    ..Recent advances in high-throughput genomics technology have expanded our ability to catalogue allelic variants in large sets of candidate genes related to premature coronary artery disease...
  25. ncbi request reprint Proteolysis regulates exposure of the IIICS-1 adhesive sequence in plasma fibronectin
    T P Ugarova
    Joseph J Jacobs Center for Thrombosis and Vascular Biology, Department of Molecular Cardiology, Cleveland Clinic Foundation, Ohio 44195, USA
    Biochemistry 35:10913-21. 1996
    ..The adhesive function of the CS-1 region in intact Fn appears to be suppressed by the native conformation of the molecule...
  26. ncbi request reprint Identification and reconstruction of the binding site within alphaMbeta2 for a specific and high affinity ligand, NIF
    L Zhang
    Joseph J Jacobs Center for Thrombosis and Vascular Biology, Department of Molecular Cardiology, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    J Biol Chem 272:17558-64. 1997
    ..Verifying this localization, when these segments were introduced into the alphaXI-domain, the resulting chimeric receptor was converted into a high affinity NIF-binding protein...
  27. ncbi request reprint The role of plasminogen in angiogenesis in vivo
    C W Oh
    Joseph J Jacobs Center for Thrombosis and Vascular Biology, Department of Molecular Cardiology, Cleveland Clinic Foundation, OH 44195, USA
    J Thromb Haemost 1:1683-7. 2003
    ..Plasminogen, by virtue of its role in the degradation of extracellular matrix proteins and by facilitation of cell migration, may contribute to angiogenesis...
  28. ncbi request reprint Identification of a novel recognition sequence for integrin alphaM beta2 within the gamma-chain of fibrinogen
    T P Ugarova
    Joseph J Jacobs Center for Thrombosis and Vascular Biology, Department of Molecular Cardiology, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    J Biol Chem 273:22519-27. 1998
    ..The juxtapositioning of these two sequences may form an unique and complex binding site for alphaM beta2...
  29. ncbi request reprint A central role for plasminogen in the inflammatory response to biomaterials
    S J Busuttil
    Case Western Reserve University and Cleveland VAMC, Cleveland, Ohio, USA
    J Thromb Haemost 2:1798-805. 2004
    ..This role is distinct from that of fibrinogen, and the two inflammatory cell types use plasminogen in different ways. Plasminogen represents a therapeutic target for controlling the inflammatory response to implanted materials...
  30. ncbi request reprint Ligand recognition by beta 3 integrins
    K Suehiro
    Department of Molecular Cardiology, Joseph J Jacobs Center for Thrombosis and Vascular Biology, Cleveland Clinic Foundation, OH 44195, USA
    Keio J Med 46:111-4. 1997
    ..Since the beta 3 integrins have multiple functions in vivo and are targets for therapy, this classification system may be useful in the design and characterization of therapeutic agents...
  31. ncbi request reprint Hypotension, autonomic failure, and cardiac hypertrophy in transgenic mice overexpressing the alpha 1B-adrenergic receptor
    M J Zuscik
    Department of Molecular Cardiology, The Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    J Biol Chem 276:13738-43. 2001
    ..These results also suggest that this receptor subtype is not involved in the classic vasoconstrictory action of alpha(1)ARs that is important in systemic regulation of blood pressure...
  32. ncbi request reprint Regulation of plasminogen binding to neutrophils
    T Herren
    Joseph J. Jacobs Center for Thrombosis and Vascular Biology, Department of Molecular Cardiology, The Cleveland Clinic Foundation, Cleveland, OH, USA
    Blood 97:1070-8. 2001
    ....
  33. ncbi request reprint The MIG-2/integrin interaction strengthens cell-matrix adhesion and modulates cell motility
    Xiaohua Shi
    Department of Pathology, University of Pittsburgh School of Medicine, 3550 Terrace Street, Pittsburgh, PA 15261, USA
    J Biol Chem 282:20455-66. 2007
    ....
  34. ncbi request reprint The specificity and function of the metal-binding sites in the integrin beta3 A-domain
    Michelle M Pesho
    Joseph J Jacobs Center for Thrombosis and Vascular Biology and Department of Molecular Cardiology, Cleveland Clinic, Cleveland, Ohio 44195, USA
    J Biol Chem 281:23034-41. 2006
    ..These results indicate that the specificities of the three metal-binding sites for divalent cations are distinct and that each site can regulate the ligand binding potential of the beta3 A-domain...
  35. ncbi request reprint Novel alpha1-adrenergic receptor signaling pathways: secreted factors and interactions with the extracellular matrix
    Ting Shi
    Department of Molecular Cardiology NB50, The Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA
    Mol Pharmacol 70:129-42. 2006
    ..Our results indicate alpha1-ARs induce the secretion of factors that interact with the extracellular matrix to regulate cell adhesion, motility and proinflammatory responses through novel signaling pathways...
  36. ncbi request reprint In vivo comparison of the inflammatory response induced by different vascular biomaterials
    Steven J Busuttil
    Department of Surgery, Case Western Reserve University and Cleveland Veterans Affairs Medical Center, Cleveland, OH, USA
    Vascular 13:230-5. 2005
    ..Stainless steel disks recruited both fewer neutrophils and fewer macrophages and support lower adherence of these cells than the other biomaterials. Copper incited an overwhelming and fatal response...
  37. ncbi request reprint Polymorphisms A387P in thrombospondin-4 and N700S in thrombospondin-1 perturb calcium binding sites
    Olga I Stenina
    Department of Molecular Cardiology, Joseph J Jacobs Center for Thrombosis, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    FASEB J 19:1893-5. 2005
    ..Since these substitutions exert the opposite effects on Ca2+ binding, a decrease in TSP-1 and an increase in TSP-4, the two TSP variants are likely to influence cardiovascular functions in distinct but yet pathogenic ways...
  38. pmc Plasminogen is an important regulator in the pathogenesis of a murine model of asthma
    Carmen M Swaisgood
    Cleveland Clinic, Department of Molecular Cardiology, NB50, 9500 Euclid Avenue, Cleveland, OH 44195, USA
    Am J Respir Crit Care Med 176:333-42. 2007
    ..Asthma is a syndrome whose common pathogenic expression is inflammation of the airways. Plasminogen plays an important role in cell migration and is also implicated in tissue remodeling, but its role in asthma has not been defined...
  39. ncbi request reprint P-selectin primes leukocyte integrin activation during inflammation
    Hai bo Wang
    Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, The Graduate School of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China
    Nat Immunol 8:882-92. 2007
    ..Our data demonstrate the functional importance of this newly identified signaling pathway mediated by P-selectin glycoprotein ligand 1...
  40. pmc Histone H2B as a functionally important plasminogen receptor on macrophages
    Riku Das
    Joseph J Jacobs Center for Thrombosis and Vascular Biology, Department of Molecular Cardiology, Cleveland Clinic, OH, USA
    Blood 110:3763-72. 2007
    ..Taken together, these data suggest that multiple Plg-Rs do contribute to Plg binding to macrophages, and among these, H2B plays a very prominent and functionally important role...
  41. pmc Analysis of Fyn function in hemostasis and alphaIIbbeta3-integrin signaling
    Kumar B Reddy
    Department of Molecular Cardiology and Joseph J Jacobs Center for Thrombosis and Vascular Biology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA
    J Cell Sci 121:1641-8. 2008
    ..Our results suggest that Fyn and Src have distinct requirements for interaction with alphaIIbbeta3; and, consequently, the two SFK can mediate different functional responses...
  42. pmc Expression, activation, and function of integrin alphaMbeta2 (Mac-1) on neutrophil-derived microparticles
    Elzbieta Pluskota
    Joseph J Jacobs Center for Thrombosis and Vascular Biology, Department of Molecular Cardiology, Cleveland Clinic, OH 44195, USA
    Blood 112:2327-35. 2008
    ..Thus, cooperation of these 2 receptor/counterreceptor systems regulates the prothrombotic properties of PMN-derived MPs...
  43. pmc Structural basis for the autoinhibition of talin in regulating integrin activation
    Esen Goksoy
    Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA
    Mol Cell 31:124-33. 2008
    ..These data define a distinct autoinhibition mechanism for talin and suggest how it controls integrin activation and cell adhesion...
  44. pmc Neutrophil apoptosis: selective regulation by different ligands of integrin alphaMbeta2
    Elzbieta Pluskota
    Joseph J Jacobs Center for Thrombosis and Vascular Biology, Department of Molecular Cardiology, Cleveland Clinic Foundation, Cleveland, OH 44195, USA
    J Immunol 181:3609-19. 2008
    ..Hence, engagement of a single integrin by closely related ligands can induce distinct signaling pathways, which can elicit distinct cellular responses...
  45. pmc Mechanism and effect of thrombospondin-4 polymorphisms on neutrophil function
    Elzbieta Pluskota
    Joseph J Jacobs Center for Thrombosis and Vascular Biology, Cleveland Clinic Foundation, Cleveland, OH 44195, USA
    Blood 106:3970-8. 2005
    ..Thus, alpha(M)beta2 plays a central role in proinflammatory activities of TSP-4 (P387) and may contribute to the prothrombotic phenotype associated with this variant...
  46. ncbi request reprint Platelet, not endothelial, P-selectin is required for neointimal formation after vascular injury
    Kai Wang
    Department of Cardiovascular Medicine, Cleveland Clinic Foundation, 9500 Euclid Ave, Cleveland, OH 44195, USA
    Arterioscler Thromb Vasc Biol 25:1584-9. 2005
    ..This study was designed to determine whether P-selectin expression on platelet, endothelial, or both surfaces is critical to the inflammatory response and neointimal formation after arterial injury...
  47. ncbi request reprint Coronary artery disease and the thrombospondin single nucleotide polymorphisms
    Olga I Stenina
    Joseph J Jacobs Center for Thrombosis and Vascular Biology and Department of Molecular Cardiology NB50, Cleveland Clinic Foundation Lerner Research Institute, 9500 Euclid Avenue, Cleveland, OH 44195, USA
    Int J Biochem Cell Biol 36:1013-30. 2004
    ....
  48. pmc Molecular and functional differences induced in thrombospondin-1 by the single nucleotide polymorphism associated with the risk of premature, familial myocardial infarction
    Natalya V Narizhneva
    Department of Molecular Cardiology, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA
    J Biol Chem 279:21651-7. 2004
    ..These data suggest a potential molecular and cellular basis for a genetic risk factor associated with early onset myocardial infarction...
  49. ncbi request reprint Integrin alphaMbeta2 orchestrates and accelerates plasminogen activation and fibrinolysis by neutrophils
    Elzbieta Pluskota
    Joseph J Jacobs Center for Thrombosis and Vascular Biology, Department of Molecular Cardiology, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    J Biol Chem 279:18063-72. 2004
    ..Thus, assembly of Plg and uPA on integrin alpha(M)beta(2) regulates Plm activity and, thereby, plays a crucial role in neutrophil-mediated thrombolysis...
  50. ncbi request reprint Increased expression of thrombospondin-1 in vessel wall of diabetic Zucker rat
    Olga I Stenina
    Joseph J Jacobs Center for Thrombosis and Vascular Biology, Department of Molecular Cardiology, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    Circulation 107:3209-15. 2003
    ..Thus, TSP-1 expression in the blood vessel wall may increase, providing a molecular link between diabetes and accelerated vascular lesion development...
  51. ncbi request reprint 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...
  52. ncbi request reprint Integrin alphaIIbbeta3 and its antagonism
    Martin J Quinn
    Joseph J Jacobs Center for Thrombosis and Vascular Biology, Department of Molecular Cardiology NB50, Cleveland Clinic Foundation, 9500 Euclid Ave, Cleveland, Ohio 44195, USA
    Arterioscler Thromb Vasc Biol 23:945-52. 2003
    ..An in-depth understanding of how antagonists engage and influence the function of alphaIIbbeta3 and platelets in the context of the new structural insights may explain its salutary and potential deleterious effects...
  53. ncbi request reprint Platelet glycoprotein IIb/IIIa inhibitors: recognition of a two-edged sword?
    Martin J Quinn
    Department of Cardiovascular Medicine, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    Circulation 106:379-85. 2002
  54. ncbi request reprint Delineation of the key amino acids involved in neutrophil inhibitory factor binding to the I-domain supports a mosaic model for the capacity of integrin alphaMbeta 2 to recognize multiple ligands
    Valentin A Ustinov
    Joseph J Jacobs Center for Thrombosis and Vascular Biology, and Department of Molecular Cardiology NB50, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    J Biol Chem 277:18769-76. 2002
    ..Thus, the alpha(M)I-domain appears to present a mosaic of exposed amino acids within surface loops on its MIDAS face, and different ligands interact with different residues to attain high affinity binding...
  55. ncbi request reprint Identification and characterization of two cation binding sites in the integrin beta 3 subunit
    Aleksandra Cierniewska-Cieslak
    Center for Microbiology and Virology, Polish Academy of Sciences, Lodz, Poland
    J Biol Chem 277:11126-34. 2002
    ..These results indicate that the ligand competent and Ca(2+)-specific inhibitory cation binding sites are distinct and reside in beta(3)-(95-373)...
  56. pmc Integrin bidirectional signaling: a molecular view
    Jun Qin
    Lerner Research Institute, Cleveland Clinic Foundation, Ohio, USA
    PLoS Biol 2:e169. 2004
  57. ncbi request reprint Thrombospondin-4 and its variants: expression and differential effects on endothelial cells
    Olga I Stenina
    Department of Molecular Cardiology, Cleveland Clinic Foundation, Cleveland, Ohio, USA
    Circulation 108:1514-9. 2003
    ..TSP-4 had not previously been implicated in vascular pathology, and very little information is available on its expression and functions...
  58. ncbi request reprint Phase II trial of GM-CSF + thalidomide in patients with androgen-independent metastatic prostate cancer
    Robert Dreicer
    Department of Hematology Oncology, Cleveland Clinic Foundation, Cleveland, OH, USA
    Urol Oncol 23:82-6. 2005
    ..We performed a Phase II trial of this combination to assess its toxicity and potential utility as an immunomodulatory approach to management of advanced prostate cancer...
  59. pmc Thrombospondin-1 up-regulates expression of cell adhesion molecules and promotes monocyte binding to endothelium
    Natalya V Narizhneva
    Department of Molecular Cardiology, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    FASEB J 19:1158-60. 2005
    ..Taken together, this study identifies a novel mechanism regulating CAM expression and subsequent monocyte binding to endothelium, which might influence the development of anti-atherosclerosis therapeutic strategies...
  60. ncbi request reprint Identity of the amino acid residues involved in C3bi binding to the I-domain supports a mosaic model to explain the broad ligand repertoire of integrin alpha M beta 2
    Valentin A Ustinov
    Joseph J Jacobs Center for Thrombosis and Vascular Biology and Department of Molecular Cardiology, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA
    Biochemistry 44:4357-64. 2005
    ..This divergence supports a mosaic model, in which different ligands engage different amino acids to bind to alpha(M)I-domain, accounting for the broad recognition capacity of integrin alpha(M)beta(2)...
  61. ncbi request reprint P-selectin binding to P-selectin glycoprotein ligand-1 induces an intermediate state of alphaMbeta2 activation and acts cooperatively with extracellular stimuli to support maximal adhesion of human neutrophils
    Yan Qing Ma
    University of Minnesota Medical School, MMC 480, 420 Delaware St SE, Minneapolis, MN 55455, USA
    Blood 104:2549-56. 2004
    ..We thus propose a model in which P-selectin induces an intermediate state of integrin activation and then cooperates with other extracellular stimuli to support maximal adhesion of human neutrophils...
  62. ncbi request reprint Regulation of integrin alphaIIbbeta3 activation by distinct regions of its cytoplasmic tails
    Yan Qing Ma
    Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA
    Biochemistry 45:6656-62. 2006
    ..Together, these data provide molecular insights into how distinct regions of the cytoplasmic tails differentially and cooperatively regulate integrin activation...
  63. pmc In vivo regulation of plasminogen function by plasma carboxypeptidase B
    Carmen M Swaisgood
    Department of Molecular Cardiology, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    J Clin Invest 110:1275-82. 2002
    ..These studies demonstrate a definitive role of pCPB as a modulator of the pivotal functions of Plg in fibrinolysis and cell migration in vivo...
  64. ncbi request reprint Convergence of the adhesive and fibrinolytic systems: recognition of urokinase by integrin alpha Mbeta 2 as well as by the urokinase receptor regulates cell adhesion and migration
    Elzbieta Pluskota
    Joseph J Jacobs Center for Thrombosis and Vascular Biology, Department of Molecular Cardiology, Cleveland Clinic Foundation, OH 44195, USA
    Blood 101:1582-90. 2003
    ..This complex may play an important role in the control of inflammatory cell migration and vascular homeostasis...
  65. ncbi request reprint MET orchestrates cancer and blood coagulation
    Olga I Stenina
    Nat Med 11:376-7. 2005
  66. ncbi request reprint Identification of histone H2B as a regulated plasminogen receptor
    Thomas Herren
    Joseph J Jacobs Center for Thrombosis and Vascular Biology, Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue NB50, Cleveland, Ohio 44195, USA
    Biochemistry 45:9463-74. 2006
    ..Thus, histone H2B represents a regulated plasminogen receptor, which contributes significantly to the plasminogen binding capacity of cells...
  67. ncbi request reprint Cell adhesion and migration assays
    Dmitry A Soloviev
    Joseph J Jacobs Center for Thrombosis and Vascular Biology, Department of Molecular Cardiology, The Cleveland Clinic Foundation, OH, USA
    Methods Mol Med 129:267-78. 2006
    ..In this chapter, several detailed protocols describing cell adhesion and migration assays are presented, and advantages and disadvantages of each method are discussed...
  68. ncbi request reprint Identification of pH-regulated antigen 1 released from Candida albicans as the major ligand for leukocyte integrin alphaMbeta2
    Dmitry A Soloviev
    Joseph J Jacobs Center for Thrombosis and Vascular Biology and Department of Molecular Cardiology, Cleveland Clinic, Cleveland, OH 44195, USA
    J Immunol 178:2038-46. 2007
    ..albicans. Together, these data indicate that Pra1p is a ligand of alpha(M)beta(2) on C. albicans and that the soluble form of Pra1p may assist the fungus in escaping host surveillance...
  69. pmc Membrane-mediated structural transitions at the cytoplasmic face during integrin activation
    Olga Vinogradova
    Structural Biology Program, Department of Molecular Cardiology, Joseph J Jacobs Center for Thrombosis and Vascular Biology, Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA
    Proc Natl Acad Sci U S A 101:4094-9. 2004
    ..These data provide a structural basis of membrane-mediated changes at the cytoplasmic face in regulating integrin activation and signaling...
  70. ncbi request reprint Association between four SNPs on chromosome 9p21 and myocardial infarction is replicated in an Italian population
    Gong Qing Shen
    Department of Molecular Cardiology, Center for Cardiovascular Genetics, Department of Cardiovascular Medicine, Cleveland Clinic, 9500 Euclid Ave, Cleveland, OH 44195, USA
    J Hum Genet 53:144-50. 2008
    ..These results indicate that chromosome 9p21 confers risk for development of MI in an Italian population...
  71. pmc An LRP8 variant is associated with familial and premature coronary artery disease and myocardial infarction
    Gong Qing Shen
    Department of Molecular Cardiology, Lerner Research Institute, Center for Cardiovascular Genetics, Cleveland, OH 44195, USA
    Am J Hum Genet 81:780-91. 2007
    ..This extensive study, involving multiple independent populations, provides the first evidence that genetic variants in LRP8 may contribute to the development of premature and familial CAD and MI...
  72. ncbi request reprint Distinct roles for the alpha and beta subunits in the functions of integrin alphaMbeta2
    Dmitry A Solovjov
    Joseph J Jacobs Center for Thrombosis and Vascular Biology, Department of Molecular Cardiology, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    J Biol Chem 280:1336-45. 2005
    ..These data indicate that each subunit of alphaMbeta2 contributes distinct properties to alphaMbeta2 and that, in most but not all cases, the response of the integrin is a composite of the functions of its individual subunits...
  73. pmc Mechanisms of integrin-vascular endothelial growth factor receptor cross-activation in angiogenesis
    Ganapati H Mahabeleshwar
    Department of Molecular Cardiology, The Cleveland Clinic, 9500 Euclid Ave, Cleveland, OH 44195, USA
    Circ Res 101:570-80. 2007
    ....
  74. pmc Leukocyte engagement of fibrin(ogen) via the integrin receptor alphaMbeta2/Mac-1 is critical for host inflammatory response in vivo
    Matthew J Flick
    Children s Hospital Research Foundation and the University of Cincinnati College of Medicine, Cincinnati, Ohio 45229 3039, USA
    J Clin Invest 113:1596-606. 2004
    ....
  75. ncbi request reprint Thrombospondins, their polymorphisms, and cardiovascular disease
    Olga I Stenina
    Joseph J Jacobs Center for Thrombosis and Vascular Biology and Department of Molecular Cardiology, Cleveland Clinic, Cleveland, OH 44195, USA
    Arterioscler Thromb Vasc Biol 27:1886-94. 2007
    ..This review seeks to summarize current information that has emerged on each of these fronts...

Research Grants38

  1. LEUKOCYTE INTEGRIN ALPHA M BETA 2
    Edward Plow; Fiscal Year: 2003
    ....
  2. LEUKOCYTE INTEGRIN ALPHA M BETA 2
    Edward Plow; Fiscal Year: 2004
    ....
  3. CLASSICAL AND ALTERNATIVE PATHWAYS OF FIBRINOLYSIS
    Edward Plow; Fiscal Year: 2004
    ..Taken together, these studies seek to bring insights into the physiological and pathophysiological roles of the plasminogen system and its regulation. ..
  4. 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. ..
  5. 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. ..
  6. CLASSICAL AND ALTERNATIVE PATHWAYS OF FIBRINOLYSIS
    Edward Plow; Fiscal Year: 2005
    ..Taken together, these studies seek to bring insights into the physiological and pathophysiological roles of the plasminogen system and its regulation. ..
  7. CLASSICAL AND ALTERNATIVE PATHWAYS OF FIBRINOLYSIS
    Edward Plow; Fiscal Year: 2006
    ..Overall, these studies will provide new insights into the functions of plasminogen and will lead to a greater understanding of the molecular and cellular events that regulate its contribution to inflammatory responses. ..
  8. Training Program in Vascular Biology and Pathology
    Edward Plow; Fiscal Year: 2007
    ....
  9. CLASSICAL AND ALTERNATIVE PATHWAYS OF FIBRINOLYSIS
    Edward Plow; Fiscal Year: 2007
    ..Overall, these studies will provide new insights into the functions of plasminogen and will lead to a greater understanding of the molecular and cellular events that regulate its contribution to inflammatory responses. ..
  10. Activation of the beta-3 integrins: Role of the kindlins
    Edward Plow; Fiscal Year: 2009
    ..We seek to define how a new set of molecules influence platelets and endothelial cells to control aggregation and angiogenesis, thereby identifying new targets for treatment and prevention of cardiovascular disease. ..
  11. CLASSICAL AND ALTERNATIVE PATHWAYS OF FIBRINOLYSIS
    Edward Plow; Fiscal Year: 2009
    ..Overall, these studies will provide new insights into the functions of plasminogen and will lead to a greater understanding of the molecular and cellular events that regulate its contribution to inflammatory responses. ..
  12. Activation of the beta-3 integrins: Role of the kindlins
    EDWARD FRANKLIN PLOW; Fiscal Year: 2010
    ..We seek to define how a new set of molecules influence platelets and endothelial cells to control aggregation and angiogenesis, thereby identifying new targets for treatment and prevention of cardiovascular disease. ..
  13. THE STRUCTURE AND FUNCTION OF PLATELET GPIIB-IIIA
    Edward Plow; Fiscal Year: 2002
    ..At the same time, these studies may have direct bearing on the use and future development of the GPIIb-IIIa blockers as antithrombotic agents. ..
  14. CLASSICAL AND ALTERNATIVE PATHWAYS OF FIBRINOLYSIS
    Edward Plow; Fiscal Year: 1999
    ..These studies also should serve as models to define the mechanisms which control proteinases and their activities at cell surfaces. ..
  15. STRUCTURE AND FUNCTION OF PLATELET GPIIB IIIIA
    Edward Plow; Fiscal Year: 1999
    ....
  16. CLASSICAL AND ALTERNATIVE PATHWAYS OF FIBRINOLYSIS
    Edward Plow; Fiscal Year: 2000
    ..These studies also should serve as models to define the mechanisms which control proteinases and their activities at cell surfaces. ..
  17. THE STRUCTURE AND FUNCTION OF PLATELET GPIIB-IIIA
    Edward Plow; Fiscal Year: 2000
    ..At the same time, these studies may have direct bearing on the use and future development of the GPIIb-IIIa blockers as antithrombotic agents. ..
  18. THE STRUCTURE AND FUNCTION OF PLATELET GPIIB-IIIA
    Edward Plow; Fiscal Year: 2001
    ..At the same time, these studies may have direct bearing on the use and future development of the GPIIb-IIIa blockers as antithrombotic agents. ..
  19. CLASSICAL AND ALTERNATIVE PATHWAYS OF FIBRINOLYSIS
    Edward Plow; Fiscal Year: 2001
    ..Taken together, these studies seek to bring insights into the physiological and pathophysiological roles of the plasminogen system and its regulation. ..
  20. LEUKOCYTE INTEGRIN ALPHA M BETA 2
    Edward Plow; Fiscal Year: 2002
    ....
  21. THE CLASSICAL AND ALTERNATIVE PATHWAYS OF FIBRINOLYSIS
    Edward Plow; Fiscal Year: 1993
    ..On an overall basis, the proposed studies will continue to provide basic insights into the complex interface between cells and fibrinolysis, an interplay that is central to hemostasis, thrombosis and bleeding disorders...
  22. LEUKOCYTE INTEGRIN ALPHA M BETA 2
    Edward Plow; Fiscal Year: 2001
    ....
  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. CLASSICAL AND ALTERNATIVE PATHWAYS OF FIBRINOLYSIS
    Edward Plow; Fiscal Year: 2003
    ..Taken together, these studies seek to bring insights into the physiological and pathophysiological roles of the plasminogen system and its regulation. ..
  25. CLASSICAL AND ALTERNATIVE PATHWAYS OF FIBRINOLYSIS
    Edward Plow; Fiscal Year: 2002
    ..Taken together, these studies seek to bring insights into the physiological and pathophysiological roles of the plasminogen system and its regulation. ..
  26. CLASSICAL AND ALTERNATIVE PATHWAYS OF FIBRINOLYSIS
    EDWARD FRANKLIN PLOW; Fiscal Year: 2010
    ..Overall, these studies will provide new insights into the functions of plasminogen and will lead to a greater understanding of the molecular and cellular events that regulate its contribution to inflammatory responses. ..