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The Importance of the Urokinase-Type Plasminogen Activator and Its Receptor for the Development and Progression of Atherosclerosis

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Role of Proteases in Cellular Dysfunction

Part of the book series: Advances in Biochemistry in Health and Disease ((ABHD,volume 8))

Abstract

Urokinase-type plasminogen activator (uPA) is a multifunctional multi-domain protein that is not only a regulator of fibrinolysis but it is also associated with several acute and chronic pathologic conditions. uPA mediates extracellular matrix (ECM) degradation and plays a pivotal role in cell adhesion, migration, and proliferation during tissue remodeling. On the cell surface, uPA binds with high affinity to its receptor, the uPAR, providing a strictly localized proteolysis of ECM proteins. The uPA/uPAR complex also activates intracellular signaling, thus regulating cellular function. An imbalance in the uPA/uPAR system leads to disorders in tissue structure and function. This book chapter summarizes recent progress in understanding the role and mechanisms of the uPA/uPAR system in the initiation and progression of atherosclerosis.

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References

  1. Libby P, Ridker PM, Hansson GK. (2011) Progress and challenges in translating the biology of atherosclerosis. Nature. 473(7347):317-325.

    Article  PubMed  CAS  Google Scholar 

  2. Businaro R, Tagliani A, Buttari B et al. (2012) Cellular and molecular players in the atherosclerotic plaque progression. Ann N Y Acad Sci. 1262:134-141.

    Article  PubMed  CAS  Google Scholar 

  3. Libby P (2012) Inflammation in atherosclerosis. Arterioscler Thromb Vasc Biol 32(9):2045-51

    Article  PubMed  CAS  Google Scholar 

  4. Yuan Y, Li P, Ye J (2012) Lipid homeostasis and the formation of macrophage-derived foam cells in atherosclerosis. Protein Cell 3:173-181.

    Article  PubMed  CAS  Google Scholar 

  5. Hoeksema MA, Stöger JL, de Winther MP (2012) Molecular pathways regulating macrophage polarization: implications for atherosclerosis. Curr Atheroscler Rep 14:254-263.

    Article  PubMed  CAS  Google Scholar 

  6. Tabas I (2012) Macrophage death and defective inflammation resolution in atherosclerosis. Nat Rev Immunol 10:36-46.

    Google Scholar 

  7. Allahverdian S, Pannu PS, Francis GA (2012) Contribution of monocyte-derived macrophages and smooth muscle cells to arterial foam cell formation. Cardiovasc Res 95:165-172.

    Article  PubMed  CAS  Google Scholar 

  8. Williams KJ, Tabas I (2005) Lipoprotein retention – and clues for atheroma regression. Arterioscler Thromb Vasc Biol 25:1536-1540.

    Article  PubMed  CAS  Google Scholar 

  9. Libby P, Geng YJ, Aikawa M et al (1996) Macrophages and atherosclerotic plaque stability. Current Opinion in Lipidology 7: 330-335.

    Article  PubMed  CAS  Google Scholar 

  10. Ghosh S, Brown R, Jones JCR et al (2000) Urinary-type Plasminogen Activator (uPA) Expression and uPA Receptor Localization Are Regulated by α3β1Integrin in Oral Keratinocytes. JBC 275: 23869-23876.

    Article  CAS  Google Scholar 

  11. Waltz DA, Fujita RM, Yang X et al. (2000) Nonproteolytic role for the urokinase receptor in cellular migration in vivo. Am J Respir Cell Mol Biol (22): 316-22.

    Article  PubMed  CAS  Google Scholar 

  12. Smith HW, Marshall CJ (2010) Regulation of cell signalling by uPAR. Nat Rev Mol Cell Biol 11:23-36.

    Article  PubMed  CAS  Google Scholar 

  13. Alfano D, Franco P, Vocca I et al (2005) The urokinase plasminogen activator and its receptor: role in cell growth and apoptosis. Thromb Haemost 93: 205-211.

    PubMed  CAS  Google Scholar 

  14. Fuhrman B (2012) The urokinase system in the pathogenesis of atherosclerosis Atherosclerosis 222:8-14.

    Article  PubMed  CAS  Google Scholar 

  15. Farris SD, Hu JH, Krishnan R et al (2011) Mechanisms of urokinase plasminogen activator (uPA)-mediated atherosclerosis: role of the uPA receptor and S100A8/A9 proteins. JBC 286: 22665-22677.

    Article  CAS  Google Scholar 

  16. Edsfeldt A, Nitulescu M, Grufman H (2012) Soluble Urokinase Plasminogen Activator Receptor is Associated With Inflammation in the Vulnerable Human Atherosclerotic Plaque. Stroke. 43: 3305-3312.

    Article  PubMed  CAS  Google Scholar 

  17. Chen W, Jin WQ, Chen LF et al (2012) Urokinase receptor surface expression regulates monocyte migration and is associated with accelerated atherosclerosis. Int J Cardiol 161:103-110

    Article  PubMed  Google Scholar 

  18. Cozen AE, Moriwaki H, Kremen M, et al (2004) Macrophage-Targeted Overexpression of Urokinase Causes Accelerated Atherosclerosis, Coronary Artery Occlusions, and Premature Death. Circulation 109: 2129-2135.

    Article  PubMed  CAS  Google Scholar 

  19. Kremen M, Krishnan R, Emery I et al (2008) Plasminogen mediates the atherogenic effects of macrophage-expressed urokinase and accelerates atherosclerosis in apoE-knockout mice. PNAS 105:17109-17114.

    Article  PubMed  CAS  Google Scholar 

  20. Krishnan R, Kremen M, Hu JH et al (2009) Level of Macrophage uPA Expression Is an Important Determinant of Atherosclerotic Lesion Growth in Apoe−/− Mice. Arterioscler Thromb Vasc Biol 29:1737-1744.

    Article  PubMed  CAS  Google Scholar 

  21. Gyöngyösi M, Glogar D, Weidinger F et al (2004) Association between plasmin activation system and intravascular ultrasound signs of plaque instability in patients with unstable angina and non-st-segment elevation myocardial infarction. Am Heart J 147:158-164.

    Article  PubMed  Google Scholar 

  22. Dellas C, Schremmer C, Hasenfuss G et al (2007) Lack of urokinase plasminogen activator promotes progression and instability of atherosclerotic lesions in apolipoprotein E-knockout mice. Thromb Haemost 98:220-227.

    PubMed  CAS  Google Scholar 

  23. Hu JH, Du L, Chu T et al (2010) Overexpression of urokinase by plaque macrophages causes histological features of plaque rupture and increases vascular matrix metalloproteinase activity in aged apolipoprotein e-null mice. Circulation 121:1637-1644.

    Article  PubMed  CAS  Google Scholar 

  24. Vincenza Carriero M, Franco P, Vocca I et al (2009) Structure, function and antagonists of urokinase-type plasminogen activator. Front Biosci 14:3782-3794.

    Article  Google Scholar 

  25. Andreasen PA, Egelund R, Petersen HH (2000) The plasminogen activation system in tumor growth, invasion, and metastasis. Cell Mol Life Sci 57:25-40.

    Article  PubMed  CAS  Google Scholar 

  26. Sitrin RG, Johnson DR, Pan PM et al (2004) Lipid raft compartmentalization of urokinase receptor signaling in human neutrophils. Am J Respir Cell Mol Biol 30:233-241

    Article  PubMed  CAS  Google Scholar 

  27. Cunningham O, Andolfo A, Santovito ML (2003) Dimerization controls the lipid raft partitioning of uPAR/CD87 and regulates its biological functions. EMBO J 22:5994-6003.

    Article  PubMed  CAS  Google Scholar 

  28. Eden G, Archinti M, Furlan F et al (2011) The urokinase receptor interactome. Curr Pharm Des 17:1874-89.

    Article  PubMed  CAS  Google Scholar 

  29. Blasi F, Carmeliet P (2002) uPAR: a versatile signalling orchestrator. Nat Rev Mol Cell Biol 3:932-943.

    Article  PubMed  CAS  Google Scholar 

  30. Blasi F, Sidenius N (2010) The urokinase receptor: focused cell surface proteolysis, cell adhesion and signaling. FEBS Lett 584:1923-1930.

    Article  PubMed  CAS  Google Scholar 

  31. Liotta LA, Goldfarb RH, Brundage R et al. (1981) Effect of plasminogen activator (urokinase), plasmin, and thrombin on glycoprotein and collagenous components of basement membrane. Cancer Res 41(11 Pt 1):4629-36.

    PubMed  CAS  Google Scholar 

  32. Gold LI, Schwimmer R, Quigley JP (1989) Human plasma fibronectin as a substrate for human urokinase. Biochem J 262:529-534.

    PubMed  CAS  Google Scholar 

  33. Naldini L, Vigna E, Bardelli A et al. (1995) Biological activation of pro-HGF (hepatocyte growth factor) by urokinase is controlled by a stoichiometric reaction. J Biol Chem 270:603-611.

    Article  PubMed  CAS  Google Scholar 

  34. Miyazawa K, Wang Y, Minoshima S et al (1998) Structural organization and chromosomal localization of the human hepatocyte growth factor activator gene – phylogenetic and functional relationship with blood coagulation factor XII, urokinase, and tissue-type plasminogen activator. Eur J Biochem 258:355-361.

    Article  PubMed  CAS  Google Scholar 

  35. Behrendt N (2004) The urokinase receptor (uPAR) and the uPAR-associated protein (uPARAP/Endo180): membrane proteins engaged in matrix turnover during tissue remodeling. Biol Chem 385:103-136.

    Article  PubMed  CAS  Google Scholar 

  36. Sturge J, Wienke D, East L et al. (2003) GPI-anchored uPAR requires Endo180 for rapid directional sensing during chemotaxis. J Cell Biol 162:789-794.

    Article  PubMed  CAS  Google Scholar 

  37. Kiyan J, Kiyan R, Haller H et al (2005) Urokinase-induced signaling in human vascular smooth muscle cells is mediated by PDGFR-beta. EMBO J 24:1787-1797.

    Article  PubMed  CAS  Google Scholar 

  38. Montuori N, Bifulco K, Carriero MV et al (2011) The cross-talk between the urokinase receptor and fMLP receptors regulates the activity of the CXCR4 chemokine receptor. Cell Mol Life Sci 68:2453-2467.

    Article  PubMed  CAS  Google Scholar 

  39. Guerrero J, Santibañez JF, González A et al (2004) EGF receptor transactivation by urokinase receptor stimulus through a mechanism involving Src and matrix metalloproteinases. Exp Cell Res 292:201-208.

    Article  PubMed  CAS  Google Scholar 

  40. Zhu Y, Bujo H, Yamazaki H et al (2004) LR11, an LDL receptor gene family member, is a novel regulator of smooth muscle cell migration. Circ Res 94:752-758

    Article  PubMed  CAS  Google Scholar 

  41. May AE, Kanse SM, Lund LR et al (1998) Urokinase receptor (CD87) regulates leukocyte recruitment via beta 2 integrins in vivo. J Exp Med 188:1029-1037.

    Article  PubMed  CAS  Google Scholar 

  42. Tabas I (2010) Macrophage death and defective inflammation resolution in atherosclerosis. Nat Rev Immunol 10:36-46.

    Article  PubMed  CAS  Google Scholar 

  43. Waltz DA, Chapman HA (1994) Reversible cellular adhesion to vitronectin linked to urokinase receptor occupancy. J Biol Chem 269:14746-14750.

    PubMed  CAS  Google Scholar 

  44. Sitrin RG, Todd RF 3rd, Albrecht E et al (1996) The urokinase receptor (CD87) facilitates CD11b/CD18-mediated adhesion of human monocytes. J Clin Invest 97:19421951.

    Article  Google Scholar 

  45. May AE, Schmidt R, Kanse SM, et al (2002) Urokinase receptor surface expression regulates monocyte adhesion in acute myocardial infarction. Blood 100:3611-3617.

    Article  PubMed  CAS  Google Scholar 

  46. Gu JM, Johns A, Morser J et al (2005) Urokinase plasminogen activator receptor promotes macrophage infiltration into the vascular wall of ApoE deficient mice. J Cell Physiol 204:73-82.

    Article  PubMed  CAS  Google Scholar 

  47. Luikart S, Masri M, Wahl D et al (2002) Urokinase is required for the formation of mactinin, an alpha-actinin fragment that promotes monocyte/macrophage maturation. Biochim Biophys Acta 1591:99-107.

    Article  PubMed  CAS  Google Scholar 

  48. Paland N, Aharoni S, Fuhrman B (2013) Urokinase-type plasminogen activator (uPA) modulates monocyte-to-macrophage differentiation and prevents Ox-LDL-induced macrophage apoptosis. Atherosclerosis 231:29-38.

    Google Scholar 

  49. Yu H, Maurer F, Medcalf RL (2002) Plasminogen activator inhibitor type 2: a regulator of monocyte proliferation and differentiation. Blood 99:2810-2818.

    Article  PubMed  CAS  Google Scholar 

  50. Stocker R, Keaney JF Jr (2005) New insights on oxidative stress in the artery wall. J Thromb Haemost 3:1825-1834.

    Article  PubMed  CAS  Google Scholar 

  51. Aviram M, Fuhrman B. et al (1998) LDL oxidation by arterial wall macrophages depends on the oxidative status in the lipoprotein and in the cells: role of prooxidants vs. antioxidants. Mol Cell Biochem 188:149-159.

    Article  PubMed  CAS  Google Scholar 

  52. Fuhrman B, Judith O, Keidar S et al (1997) Increased uptake of LDL by oxidized macrophages is the result of an initial enhanced LDL receptor activity and of a further progressive oxidation of LDL. Free Radic Biol Med 23:34-46.

    Article  PubMed  CAS  Google Scholar 

  53. Fuhrman B, Volkova N, Aviram M (2002) Oxidative stress increases the expression of the CD36 scavenger receptor and the cellular uptake of oxidized low-density lipoprotein in macrophages from atherosclerotic mice: protective role of antioxidants and of paraoxonase. Atherosclerosis 161:307-316.

    Article  PubMed  CAS  Google Scholar 

  54. Fuhrman B, Shiner M, Volkova N et al (2004) Cell-induced copper ion-mediated low density lipoprotein oxidation increases during in vivo monocyte-to-macrophage differentiation. Free Radic Biol Med 37:259-271.

    Article  PubMed  CAS  Google Scholar 

  55. Fuhrman B, Partoush A, Volkova N et al (2008) Ox-LDL induces monocyte-to-macrophage differentiation in vivo: Possible role for the macrophage colony stimulating factor receptor (M-CSF-R). Atherosclerosis 196:598-607.

    Article  PubMed  CAS  Google Scholar 

  56. Shiner M, Fuhrman B, Aviram M (2004) Paraoxonase 2 (PON2) expression is upregulated via a reduced-nicotinamide-adenine-dinucleotide-phosphate (NADPH)-oxidase-dependent mechanism during monocytes differentiation into macrophages. Free Radic Biol Med 37:2052-2063.

    Article  PubMed  CAS  Google Scholar 

  57. Fuhrman B, Khateeb J, Shiner M et al (2008) Urokinase plasminogen activator upregulates paraoxonase 2 expression in macrophages via an NADPH oxidase-dependent mechanism. Arterioscler Thromb Vasc Biol 28:1361-1367.

    Article  PubMed  CAS  Google Scholar 

  58. Fuhrman B, Gantman A, Khateeb J et al (2009) Urokinase activates macrophage PON2 gene transcription via the PI3K/ROS/MEK/SREBP-2 signalling cascade mediated by the PDGFR-beta. Cardiovasc Res 84(1):145-54.

    Article  PubMed  CAS  Google Scholar 

  59. Khateeb J, Kiyan Y, Aviram M et al. (2012) Urokinase-type plasminogen activator downregulates paraoxonase 1 expression in hepatocytes by stimulating peroxisome proliferator-activated receptor-γ nuclear export. Arterioscler Thromb Vasc Biol 32:449-458.

    Article  PubMed  CAS  Google Scholar 

  60. Fuhrman B, Koren L, Volkova N et al. (2002) Atorvastatin therapy in hypercholesterolemic patients suppresses cellular uptake of oxidized-LDL by differentiating monocytes. Atherosclerosis 164(1):179-85.

    Article  PubMed  CAS  Google Scholar 

  61. Ohwaki K, Bujo H, Jiang M et al (2007) A secreted soluble form of LR11, specifically expressed in intimal smooth muscle cells, accelerates formation of lipid-laden macrophages. Arterioscler Thromb Vasc Biol 27:1050-106.

    Article  PubMed  CAS  Google Scholar 

  62. Fuhrman B, Nitzan O, Karry R et al (2007) Urokinase plasminogen activator (uPA) stimulates cholesterol biosynthesis in macrophages through activation of SREBP-1 in a PI3-kinase and MEK-dependent manner. Atherosclerosis 195:e108-e116.

    Article  PubMed  CAS  Google Scholar 

  63. Angeli V, Llodrá J, Rong JX et al (2004) Dyslipidemia associated with atherosclerotic disease systemically alters dendritic cell mobilization. Immunity 21:561-574.

    Article  PubMed  CAS  Google Scholar 

  64. Kiyan J, Smith G, Haller H et al (2009) Urokinase-receptor-mediated phenotypic changes in vascular smooth muscle cells require the involvement of membrane rafts. Biochem J 423:343-351.

    Article  PubMed  CAS  Google Scholar 

  65. Kiian I, Tkachuk N, Haller H et al (2003) Urokinase-induced migration of human vascular smooth muscle cells requires coupling of the small GTPases RhoA and Rac1 to the Tyk2/PI3-K signalling pathway. Thromb Haemost 89:904-914.

    PubMed  CAS  Google Scholar 

  66. Kusch A, Tkachuk S, Lutter S et al (2002) Monocyte-expressed urokinase regulates human vascular smooth muscle cell migration in a coculture model. Biol Chem 383:217-221.

    Article  PubMed  CAS  Google Scholar 

  67. Goncharova EA, Vorotnikov AV, Gracheva EO et al (2002) Activation of p38 MAP-kinase and caldesmon phosphorylation are essential for urokinase-induced human smooth muscle cell migration. Biol Chem 383:115-126.

    Article  PubMed  CAS  Google Scholar 

  68. Mukhina S, Stepanova V, Traktouev D et al (2000) The chemotactic action of urokinase on smooth muscle cells is dependent on its kringle domain. Characterization of interactions and contribution to chemotaxis. J Biol Chem 275:16450-16458

    Article  PubMed  CAS  Google Scholar 

  69. Plekhanova OS, Parfyonova YV, Bibilashvily RSh et al. (2000) Urokinase plasminogen activator enhances neointima growth and reduces lumen size in injured carotid arteries. J Hypertens 18:1065-1069.

    Google Scholar 

  70. Nicholl SM, Roztocil E, Davies MG (2005) Urokinase-induced smooth muscle cell responses require distinct signaling pathways: a role for the epidermal growth factor receptor. J Vasc Surg 41:672-681.

    Article  PubMed  Google Scholar 

  71. Menshikov M, Plekhanova O, Cai H et al (2006) Urokinase plasminogen activator stimulates vascular smooth muscle cell proliferation via redox-dependent pathways. Arterioscler Thromb Vasc Biol 26(4):801-7.

    Article  PubMed  CAS  Google Scholar 

  72. Plekhanova OS, Men’shikov MY, Bashtrykov PP et al (2006) Urokinase induces ROS production in vascular smooth muscle cells. Bull Exp Biol Med 142:304-307.

    Article  PubMed  CAS  Google Scholar 

  73. Tabas I (2004) Apoptosis and plaque destabilization in atherosclerosis: the role of macrophage apoptosis induced by cholesterol. Cell Death Differ 11 Suppl 1:S12-16.

    Article  PubMed  CAS  Google Scholar 

  74. Scull CM, Tabas I (2011) Mechanisms of ER stress-induced apoptosis in atherosclerosis Arterioscler Thromb Vasc Biol. 31:2792-2797.

    Article  PubMed  CAS  Google Scholar 

  75. Xu F, Sun Y, Chen Y et al (2009) Endothelial cell apoptosis is responsible for the formation of coronary thrombotic atherosclerotic plaques. Tohoku J Exp Med 218:25-33.

    Article  PubMed  Google Scholar 

  76. Clarke M, Bennett M (2006) The emerging role of vascular smooth muscle cell apoptosis in atherosclerosis and plaque stability. Am J Nephrol 26:531-535.

    Article  PubMed  Google Scholar 

  77. Thim T, Hagensen MK, Bentzon JF et al (2008) From vulnerable plaque to atherothrombosis. J Intern Med 263:506-516.

    Article  PubMed  CAS  Google Scholar 

  78. Neri T, Cordazzo C, Carmazzi Y et al (2012) Effects of peroxisome proliferator-activated receptor-γ agonists on the generation of microparticles by monocytes/macrophages. Cardiovasc Res 94:537-544.

    Article  PubMed  CAS  Google Scholar 

  79. Lindstedt KA, Leskinen MJ, Kovanen PT (2004) Proteolysis of the pericellular matrix: a novel element determining cell survival and death in the pathogenesis of plaque erosion and rupture. Arterioscler Thromb Vasc Biol 24:1350-1358.

    Article  PubMed  CAS  Google Scholar 

  80. Siefert SA, Sarkar R (2012) Matrix metalloproteinases in vascular physiology and disease. Vascular. 20:210-216.

    Article  PubMed  Google Scholar 

  81. Gough PJ, Gomez IG, Wille PT et al (2006) Macrophage expression of active MMP-9 induces acute plaque disruption in apoE-deficient mice. J Clin Invest 116:59-69.

    Article  PubMed  CAS  Google Scholar 

  82. Svensson PA, Olson FJ, Hägg DA, et al (2008) Urokinase-type plasminogen activator receptor is associated with macrophages and plaque rupture in symptomatic carotid atherosclerosis. Int J Mol Med 22:459-464.

    PubMed  Google Scholar 

  83. Prager GW, Mihaly J, Brunner PM et al (2009) Urokinase mediates endothelial cell survival via induction of the X-linked inhibitor of apoptosis protein. Blood 113:1383-1390.

    Article  PubMed  CAS  Google Scholar 

  84. Rossignol P, Anglès-Cano E, Lijnen HR (2006) Plasminogen activator inhibitor-1 impairs plasminogen activation-mediated vascular smooth muscle cell apoptosis. Thromb Haemost 96:665-670.

    PubMed  CAS  Google Scholar 

  85. Pillay V, Dass CR, Choong PF (2007) The urokinase plasminogen activator receptor as a gene therapy target for cancer. Trends Biotechnol 25:33-39.

    Article  PubMed  CAS  Google Scholar 

  86. Lamfers ML, Lardenoye JH, de Vries MR et al (2001) In vivo suppression of restenosis in balloon-injured rat carotid artery by adenovirus-mediated gene transfer of the cell surface-directed plasmin inhibitor ATF.BPTI. Gene Ther 8:534-541.

    Article  PubMed  CAS  Google Scholar 

  87. Lamfers ML, Grimbergen JM, Aalders MC et al (2002) Gene transfer of the urokinase-type plasminogen activator receptor-targeted matrix metalloproteinase inhibitor TIMP-1.ATF suppresses neointima formation more efficiently than tissue inhibitor of metalloproteinase-1. Circ Res 91:945-952.

    Article  PubMed  CAS  Google Scholar 

  88. Eefting D, Seghers L, Grimbergen JM et al (2010) A novel urokinase receptor-targeted inhibitor for plasmin and matrix metalloproteinases suppresses vein graft disease. Cardiovasc Res 88:367-375.

    Article  PubMed  CAS  Google Scholar 

  89. Ganné F, Vasse M, Beaudeux JL et al (2000) Cerivastatin, an inhibitor of HMG-CoA reductase, inhibits urokinase/urokinase-receptor expression and MMP-9 secretion by peripheral blood monocytes – a possible protective mechanism against atherothrombosis. Thromb Haemost 84:680-688.

    PubMed  Google Scholar 

  90. Stach K, Nguyen XD, Lang S et al (2012) Simvastatin and atorvastatin attenuate VCAM-1 and uPAR expression on human endothelial cells and platelet surface expression of CD40 ligand. Cardiol J 19:20-28.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. The Lipid Research Laboratory, Technion Faculty of Medicine and Rambam Medical Center, Haifa, 31096, Israel

    Nicole Paland & Bianca Fuhrman

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  1. Nicole Paland
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  2. Bianca Fuhrman
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Correspondence to Bianca Fuhrman .

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Editors and Affiliations

  1. St. Boniface Hosp. Research, Univ. of Ma Institute of Cardiovascular Sciences, Winnipeg, Manitoba, Canada

    Naranjan S. Dhalla

  2. Dept of Biochemistry and Biophysics, University of Kalyani, Kalyani, West Bengal, India

    Sajal Chakraborti

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Paland, N., Fuhrman, B. (2014). The Importance of the Urokinase-Type Plasminogen Activator and Its Receptor for the Development and Progression of Atherosclerosis. In: Dhalla, N., Chakraborti, S. (eds) Role of Proteases in Cellular Dysfunction. Advances in Biochemistry in Health and Disease, vol 8. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-9099-9_14

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