The endothelial cell protein C receptor: Its role in thrombosis

Thrombosis Research

Volumn 128, Issue 5, 2011, Pages 410-416

  Navarro, Silvia ^a   Bonet, Elena ^a   Estellés, Amparo ^a   Montes, Ramón ^b   Hermida, José ^b   Martos, Laura ^a   España, Francisco ^a   Medina, Pilar ^a  

^a HOSPITAL UNIVERSITARIO LA FE   (Spain)

^b UNIVERSITY OF NAVARRA   (Spain)

Author keywords

activated protein C; endothelial protein C receptor; factor VII; myocardial infarction; venous thrombosis

Indexed keywords

AUTOANTIBODY; BLOOD CLOTTING FACTOR 5A; BLOOD CLOTTING FACTOR 8A; ENDOTHELIAL PROTEIN C RECEPTOR; THROMBIN; THROMBOMODULIN;

ARTERY THROMBOSIS; CELL PROTECTION; CELL SURFACE; DOWN REGULATION; ENDOTHELIUM CELL; HAPLOTYPE; MUTATION; PRIORITY JOURNAL; RECEPTOR BINDING; REVIEW; RISK; SINGLE NUCLEOTIDE POLYMORPHISM; THROMBOSIS; VENOUS THROMBOEMBOLISM;

BLOOD COAGULATION FACTORS; HUMANS; MUTATION; RECEPTORS, CELL SURFACE; THROMBOSIS;

EID: 80055095617     PISSN: 00493848     EISSN: 18792472     Source Type: Journal    
DOI: 10.1016/j.thromres.2011.08.001     Document Type: Review

References (113)

1. F.J. Walker Regulation of activated protein C by a new protein. A possible function for bovine protein S J Biol Chem 255 1980 5521 5524
2. J.H. Griffin, B. Evatt, T.S. Zimmerman, A.J. Kleiss, and C. Wideman Deficiency of protein C in congenital thrombotic disease J Clin Invest 68 1981 1370 1373 (Pubitemid 12235040)
3. C.A. Fulcher, J.E. Gardiner, J.H. Griffin, and T.S. Zimmerman Proteolytic inactivation of human factor VIII procoagulant protein by activated human protein C and its analogy with factor V Blood 63 1984 486 489 (Pubitemid 14188903)
4. J.H. Griffin, J.A. Fernandez, A.J. Gale, and L.O. Mosnier Activated protein C J Thromb Haemost 5 Suppl 1 2007 73 80 (Pubitemid 46958820)
5. D.J. Stearns-Kurosawa, S. Kurosawa, J.S. Mollica, G.L. Ferrell, and C.T. Esmon The endothelial cell protein C receptor augments protein C activation by the thrombin-thrombomodulin complex Proc Natl Acad Sci USA 93 1996 10212 10216 (Pubitemid 26314601)
6. F.B. Taylor Jr., G.T. Peer, M.S. Lockhart, G. Ferrell, and C.T. Esmon Endothelial cell protein C receptor plays an important role in protein C activation in vivo Blood 97 2001 1685 1688 (Pubitemid 32217234)
7. M.N. Centelles, C. Puy, J. López-Sagaseta, K. Fukudome, R. Montes, and J. Hermida Blocking endothelial protein C receptor (EPCR) accelerates thrombus development in vivo Thromb Haemost 103 2010 1239 1244
8. C.T. Esmon The roles of protein C and thrombomodulin in the regulation of blood coagulation J Biol Chem 264 1989 4743 4746 (Pubitemid 19092874)
9. Z. Laszik, A. Mitro, F.B. Taylor, G. Ferrell, and C.T. Esmon Human protein C receptor is present primarily on endothelium of large blood vessels: implications for the control of the protein C pathway Circulation 96 1997 3633 3640 (Pubitemid 27513443)
10. F. España, P. Medina, S. Navarro, E. Zorio, A. Estellés, and J. Aznar The multifunctional protein C system Curr Med Chem Cardiovasc Hematol Agents 3 2005 119 131 (Pubitemid 40514787)
11. M. Riewald, R.J. Petrovan, A. Donner, B.M. Mueller, and W. Ruf Activation of endothelial cell protease activated receptor 1 by the protein C pathway Science 296 2002 1880 1882 (Pubitemid 34596276)
12. S.R. Coughlin Protease-activated receptors in hemostasis, thrombosis and vascular biology J Thromb Haemost 3 2005 1800 1814 (Pubitemid 41716567)
13. J.S. Bae, L. Yang, and A.R. Rezaie Receptors of the protein C activation and activated protein C signaling pathways are colocalized in lipid rafts of endothelial cells Proc Natl Acad Sci USA 104 2007 2867 2872 (Pubitemid 46327971)
14. F. Niessen, C. Furlan-Freguia, J.A. Fernandez, L.O. Mosnier, F.J. Castellino, and H. Weiler Endogenous EPCR/aPC-PAR1 signaling prevents inflammation-induced vascular leakage and lethality Blood 113 2009 2859 2866
15. M. Bezuhly, R. Cullen, C.T. Esmon, S.F. Morris, K.A. West, and B. Johnston Role of activated protein C and its receptor in inhibition of tumor metastasis Blood 113 2009 3371 3374
16. T. Cheng, D. Liu, J.H. Griffin, J.A. Fernández, F. Castellino, and E.D. Rosen Activated protein C blocks p53-mediated apoptosis in ischemic human brain endothelium and is neuroprotective Nat Med 9 2003 338 342 (Pubitemid 36362790)
17. R.M. Bertina, A.W. Broekmans, I.K. van der Linden, and K. Mertens Protein C deficiency in a Dutch family with thrombotic disease Thromb Haemost 48 1982 1 5 (Pubitemid 12059109)
18. A. Estellés, I. García-Plaza, A. Dasí, J. Aznar, M. Duart, and G. Sanz Severe inherited "homozygous" protein C deficiency in a newborn infant Thromb Haemost 52 1984 53 56 (Pubitemid 14003811)
19. H.P. Schwarz, M. Fischer, P. Hopmeier, M.A. Batard, and J.H. Griffin Plasma protein S deficiency in familial thrombotic disease Blood 64 1984 1297 1300 (Pubitemid 15224546)
20. P.C. Comp, R.R. Nixon, M.R. Cooper, and C.T. Esmon Familial protein S deficiency is associated with recurrent thrombosis J Clin Invest 74 1984 2082 2088 (Pubitemid 15197352)
21. L. Engesser, A.W. Broekmans, E. Briët, E.J. Brommer, and R.M. Bertina Hereditary protein S deficiency: clinical manifestations Ann Intern Med 106 1987 677 682 (Pubitemid 17067983)
22. F. España, E. Zorio, P. Medina, A. Osa, A. Estellés, and M. Palencia Low levels of circulating activated protein C are a risk factor for myocardial infarction Pathophysiol Haemost Thromb 32 Suppl 2 2002 61
23. F. España, P. Medina, S. Navarro, A. Estellés, and J. Aznar Inherited abnormalities in the protein C activation pathway Pathophysiol Haemost Thromb 32 2002 241 244 (Pubitemid 37490545)
24. E. Zorio, S. Navarro, P. Medina, A. Estellés, A. Osa, and J. Rueda Circulating activated protein C is reduced in young survivors of myocardial infarction and inversely correlates with the severity of coronary lesions J Thromb Haemost 4 2006 1530 1536
25. R.M. Bertina Molecular risk factors for thrombosis Thromb Haemost 82 1999 601 609
26. K. Fukudome, and C.T. Esmon Identification, cloning, and regulation of a novel endothelial cell protein C/activated protein C receptor J Biol Chem 269 1994 26486 26491 (Pubitemid 24328474)
27. Z.G. Laszik, X.J. Zhou, G.L. Ferrell, F.G. Silva, and C.T. Esmon Down-regulation of endothelial expression of endothelial cell protein C receptor and thrombomodulin in coronary atherosclerosis Am J Pathol 159 2001 797 802 (Pubitemid 32847169)
28. L. Galligan, W. Livingstone, Y. Volkov, K. Hokamp, C. Murphy, and M. Lawler Characterization of protein C receptor expression in monocytes Br J Haematol 115 2001 408 414 (Pubitemid 34203510)
29. D.H. Sturn, N.C. Kaneider, C. Feistritzer, A. Djanani, K. Fukudome, and C.J. Wiedermann Expression and function of the endothelial protein C receptor in human neutrophils Blood 102 2003 1499 1505 (Pubitemid 36988062)
30. L.O. Mosnier, and J.H. Griffin Protein C anticoagulant activity in relation to anti-inflammatory and anti-apoptotic activities Front Biosci 11 2006 2381 2399 (Pubitemid 43806554)
31. C. Feistritzer, B.A. Mosheimer, D.H. Sturn, M. Riewald, J.R. Patsch, and C.J. Wiedermann Endothelial protein C receptor-dependent inhibition of migration of human lymphocytes by protein C involves epidermal growth factor receptor J Immunol 176 2006 1019 1025 (Pubitemid 43099702)
32. T. Kurata, T. Hayashi, T. Yoshikawa, T. Okamoto, K. Yoshida, and T. Iino Activated protein C stimulates osteoblast proliferation via endothelial protein C receptor Thromb Res 125 2010 184 191
33. M. Nakamura, E.C. Gabazza, I. Imoto, Y. Yano, O. Taguchi, and N. Horiki Anti-inflammatory effect of activated protein C in gastric epithelial cells J Thromb Haemost 3 2005 2721 2729 (Pubitemid 41819801)
34. M.T. Jackson, M.M. Smith, S.M. Smith, C.J. Jackson, M. Xue, and C.B. Little Activation of cartilage matrix metalloproteinases by activated protein C Arthritis Rheum 60 2009 780 791
35. M. Xue, M.M. Smith, C.B. Little, P. Sambrook, L. March, and C.J. Jackson Activated protein C mediates a healing phenotype in cultured tenocytes J Cell Mol Med 13 2009 749 757
36. M. Xue, D. Campbell, and C.J. Jackson Protein C is an autocrine growth factor for human skin keratinocytes J Biol Chem 282 2007 13610 13616 (Pubitemid 47100554)
37. E. Bretschneider, B. Uzonyi, A.A. Weber, J.W. Fischer, R. Pape, and K. Lotzer Human vascular smooth muscle cells express functionally active endothelial cell protein C receptor Circ Res 100 2007 255 262 (Pubitemid 46208726)
38. E. Kerschen, I. Hernández, M. Zogg, S. Jia, M.J. Hessner, and J.A. Fernández Activated protein C targets CD8+ dendritic cells to reduce the mortality of endotoxemia in mice J Clin Invest 120 2010 3167 3178
39. A.B. Balazs, A.J. Fabian, C.T. Esmon, and R.C. Mulligan Endothelial protein C receptor (CD201) explicitly identifies hematopoietic stem cells in murine bone marrow Blood 107 2006 2317 2321 (Pubitemid 43345550)
40. J. Wang, L. Yang, A.R. Rezaie, and J. Li Activated protein C protects against myocardial ischemic/reperfusion injury through AMP-activated protein kinase signaling J Thromb Haemost 9 2011 1308 1317
41. K. Fukudome, and C.T. Esmon Molecular cloning and expression of murine and bovine endothelial cell protein C/activated protein C receptor (EPCR). The structural and functional conservation in human, bovine, and murine EPCR J Biol Chem 270 1995 5571 5577
42. R.E. Simmonds, and D.A. Lane Structural and functional implications of the intron/exon organization of the human endothelial cell protein C/activated protein C receptor (EPCR) gene: comparison with the structure of CD1/major histocompatibility complex alpha1 and alpha2 domains Blood 94 1999 632 641 (Pubitemid 29323877)
43. T. Hayashi, H. Nakamura, A. Okada, S. Takebayashi, T. Wakita, and H. Yuasa Organization and chromosomal localization of the human endothelial protein C receptor gene Gene 238 1999 367 373 (Pubitemid 29447032)
44. V. Oganesyan, N. Oganesyan, S. Terzyan, D. Qu, Z. Dauter, and N.L. Esmon The crystal structure of the endothelial protein C receptor and a bound phospholipid J Biol Chem 277 2002 24851 24854 (Pubitemid 34951783)
45. C.T. Esmon, J.M. Gu, J. Xu, D. Qu, D.J. Stearns-Kurosawa, and S. Kurosawa Regulation and functions of the protein C anticoagulant pathway Haematologica 84 1999 363 368 (Pubitemid 29474352)
46. C.T. Esmon The endothelial cell protein C receptor Thromb Haemost 83 2000 639 643 (Pubitemid 30248505)
47. S. Kurosawa, D.J. Stearns-Kurosawa, N. Hidari, and C.T. Esmon Identification of functional endothelial protein C receptor in human plasma J Clin Invest 100 1997 411 418 (Pubitemid 27349089)
48. D. Qu, Y. Wang, N.L. Esmon, and C.T. Esmon Regulated endothelial protein C receptor shedding is mediated by tumor necrosis factor-alpha converting enzyme/ADAM17 J Thromb Haemost 5 2007 395 402 (Pubitemid 46139466)
49. F. Peiretti, M. Canault, P. Morange, M.C. Alessi, and G. Nalbone The two sides of ADAM17 in inflammation: implications in atherosclerosis and obesity Med Sci (Paris) 25 2009 45 50
50. B. Nan, P. Lin, A.B. Lumsden, Q. Yao, and C. Chen Effects of TNF-alpha and curcumin on the expression of thrombomodulin and endothelial protein C receptor in human endothelial cells Thromb Res 115 2005 417 426 (Pubitemid 40283487)
51. M. Menschikowski, A. Hagelgans, G. Eisenhofer, and G. Siegert Regulation of endothelial protein C receptor shedding by cytokines is mediated through differential activation of MAP kinase signaling pathways Exp Cell Res 315 2009 2673 2682
52. M. Menschikowski, A. Hagelgans, O. Tiebel, L. Klinsmann, G. Eisenhofer, and G. Siegert Expression and shedding of endothelial protein C receptor in prostate cancer cells Cancer Cell Int 11 2011 4
53. P.C. Liaw, P.F. Neuenschwander, M.D. Smirnov, and C.T. Esmon Mechanisms by which soluble endothelial cell protein C receptor modulates protein C and activated protein C function J Biol Chem 275 2000 5447 5452 (Pubitemid 30115177)
54. S. Kurosawa, C. Esmon, and D. Stearns-Kurosawa The soluble endothelial protein C receptor binds to activated neutrophils: involvement of proteinase-3 and CD11b/CD18 J Immunol 165 2000 4697 4703
55. C.T. Esmon The protein C pathway Chest 124 2003 26S 32S (Pubitemid 37128433)
56. A. Villegas-Méndez, R. Montes, L.R. Ambrose, A.N. Warrens, M. Laffan, and D.A. Lane Proteolysis of the endothelial cell protein C receptor by neutrophil proteinase 3 J Thromb Haemost 5 2007 980 988 (Pubitemid 46691727)
57. D.J. Stearns-Kurosawa, C. Burgin, D. Parker, P. Comp, and S. Kurosawa Bimodal distribution of soluble endothelial protein C receptor levels in healthy populations J Thromb Haemost 1 2003 855 856
58. D.J. Stearns-Kurosawa, K. Swindle, and A. D'Angelo Della Valle P, Fattorini A, Caron N, Grimaux M, Woodhams B and Kurosawa S. Plasma levels of endothelial protein C receptor respond to anticoagulant treatment Blood 99 2002 526 530 (Pubitemid 34533088)
59. M. Menschikowski, A. Hagelgans, U. Hempel, P. Lattke, I. Ismailov, and G. Siegert On interaction of activated protein C with human aortic smooth muscle cells attenuating the secretory group IIA phospholipase A2 expression Thromb Res 122 2008 69 76 (Pubitemid 351601843)
60. J.S. Bae, and A.R. Rezaie Thrombin and activated protein C inhibit the expression of secretory group IIA phospholipase A(2) in the TNF-alpha-activated endothelial cells by EPCR and PAR-1 dependent mechanisms Thromb Res 125 2010 e9 e15
61. S. Kurosawa, D.J. Stearns-Kurosawa, C.W. Carson, A. D'Angelo, P. Della Valle, and C.T. Esmon Plasma levels of endothelial cell protein C receptor are elevated in patients with sepsis and systemic lupus erythematosus: lack of correlation with thrombomodulin suggests involvement of different pathological processes Blood 91 1998 725 727 (Pubitemid 28053403)
62. C.A. Sesin, X. Yin, C.T. Esmon, J.P. Buyon, and R.M. Clancy Shedding of endothelial protein C receptor contributes to vasculopathy and renal injury in lupus: in vivo and in vitro evidence Kidney Int 68 2005 110 120 (Pubitemid 43181368)
63. B. Saposnik, J.L. Reny, P. Gaussem, J. Emmerich, M. Aiach, and S. Gandrille A haplotype of the EPCR gene is associated with increased plasma levels of sEPCR and is a candidate risk factor for thrombosis Blood 103 2004 1311 1318 (Pubitemid 38168642)
64. P. Medina, S. Navarro, A. Estellés, A. Vayá, B. Woodhams, and Y. Mira Contribution of polymorphisms in the endothelial protein C receptor gene to soluble endothelial protein C receptor and circulating activated protein C levels, and thrombotic risk Thromb Haemost 91 2004 905 911 (Pubitemid 38647493)
65. S. Uitte de Willige, V. Van Marion, F.R. Rosendaal, H.L. Vos, M.C. de Visser, and R.M. Bertina Haplotypes of the EPCR gene, plasma sEPCR levels and the risk of deep venous thrombosis J Thromb Haemost 2 2004 1305 1310 (Pubitemid 40186125)
66. B. Saposnik, E. Lesteven, A. Lokajczyk, C.T. Esmon, M. Aiach, and S. Gandrille Alternative mRNA is favored by the A3 haplotype of the EPCR gene PROCR and generates a novel soluble form of EPCR in plasma Blood 111 2008 3442 3451
67. E. Molina, J. Hermida, J. López-Sagaseta, C. Puy, and R. Montes The functional properties of a truncated form of endothelial cell protein C receptor generated by alternative splicing Haematologica 93 2008 878 884 (Pubitemid 351821724)
68. L.M. Regan, J.S. Mollica, A.R. Rezaie, and C.T. Esmon The interaction between the endothelial cell protein C receptor and protein C is dictated by the gamma-carboxyglutamic acid domain of protein C J Biol Chem 272 1997 26279 26284 (Pubitemid 27458839)
69. R.J. Preston, A. Villegas-Méndez, Y.H. Sun, J. Hermida, P. Simioni, and H. Philippou Selective modulation of protein C affinity for EPCR and phospholipids by Gla domain mutation FEBS J 272 2005 97 108 (Pubitemid 40083070)
70. R.J. Preston, E. Ajzner, C. Razzari, S. Karageorgi, S. Dua, and B. Dahlbäck Multifunctional specificity of the protein C/activated protein C Gla domain J Biol Chem 281 2006 28850 28857 (Pubitemid 44507028)
71. S. Ghosh, U.R. Pendurthi, A. Steinoe, C.T. Esmon, and L.V. Rao Endothelial cell protein C receptor acts as a cellular receptor for factor VIIa on endothelium J Biol Chem 282 2007 11849 11857 (Pubitemid 47100682)
72. J. López-Sagaseta, R. Montes, C. Puy, N. Díez, K. Fukudome, and J. Hermida Binding of factor VIIa to the endothelial cell protein C receptor reduces its coagulant activity J Thromb Haemost 5 2007 1817 1824 (Pubitemid 47288936)
73. R.C. Nayak, P. Sen, S. Ghosh, R. Gopalakrishnan, C.T. Esmon, and U.R. Pendurthi Endothelial cell protein C receptor cellular localization and trafficking: potential functional implications Blood 114 2009 1974 1986
74. U.R. Pendurthi, and L.V. Rao Factor VIIa interaction with endothelial cells and endothelial cell protein C receptor Thromb Res 125 Suppl 1 2010 S19 S22
75. C. Puy, J. López-Sagaseta, J. Hermida, and R. Montes The endothelial cells downregulate the generation of factor VIIa through EPCR binding Br J Haematol 149 2010 111 117
76. P. Sen, R. Gopalakrishnan, H. Kothari, S. Keshava, C.A. Clark, and C.T. Esmon Factor VIIa bound to endothelial cell protein C receptor activates protease activated receptor-1 and mediates cell signaling and barrier protection Blood 117 2011 3199 3208
77. J. Disse, H.H. Petersen, K.S. Larsen, E. Persson, N. Esmon, and C.T. Esmon The endothelial protein C receptor supports tissue factor ternary coagulation initiation complex signaling through protease-activated receptors J Biol Chem 286 2011 5756 5767
78. V. Hurtado, R. Montes, J.C. Gris, M.L. Bertolaccini, A. Alonso, and M.A. Martínez-González Autoantibodies against EPCR are found in antiphospholipid syndrome and are a risk factor for fetal death Blood 104 2004 1369 1374 (Pubitemid 39166513)
79. A. van Hylckama Vlieg, R. Montes, F.R. Rosendaal, and J. Hermida Autoantibodies against endothelial protein C receptor and the risk of a first deep vein thrombosis J Thromb Haemost 5 2007 1449 1454 (Pubitemid 46965374)
80. R. Montes, V. Hurtado, A. Alonso, L. Foco, P. Zonzin, and P.M. Mannucci Autoantibodies against the endothelial receptor of protein C are associated with acute myocardial infarction in young women J Thromb Haemost 3 2005 1454 1458 (Pubitemid 41725203)
81. G. Lavigne-Lissalde, E. Cochery-Nouvellon, G. Granier, I. Quere, and J.C. Gris Diffuse skin necrosis in a patient with an anti-endothelial cell protein C receptor autoantibody which blocks protein C activation J Thromb Haemost 3 2005 413 415 (Pubitemid 41623644)
82. F. Espana, A. Vaya, Y. Mira, P. Medina, A. Estelles, and P. Villa Low level of circulating activated protein C is a risk factor for venous thromboembolism Thromb Haemost 86 2001 1368 1373 (Pubitemid 34007506)
83. G. Merati, E. Biguzzi, N. Oganesyan, R. Fetiveau, D. Qu, and P. Bucciarelli A 23bp insertion in the endothelial protein C receptor (EPCR) gene in patients with myocardial infarction and deep vein thrombosis Supplement to the journal Thromb Haemost 507 1999
84. E. Biguzzi, G. Merati, P.C. Liaw, P. Bucciarelli, N. Oganesyan, and D. Qu A 23 bp insertion in the endothelial protein C receptor (EPCR) gene impairs EPCR function Thromb Haemost 86 2001 945 948 (Pubitemid 32979129)
85. M. von Depka, A. Czwalinna, R. Eisert, C. Wermes, I. Scharrer, and A. Ganser Prevalence of a 23 bp insertion in exon 3 of the endothelial cell protein C receptor gene in venous thrombophilia Thromb Haemost 86 2001 1360 1362 (Pubitemid 34007504)
86. S.R. Poort, H.L. Vos, F.R. Rosendaal, and R.M. Bertina The endothelial protein C receptor (EPCR) 23 bp insert mutation and the risk of venous thrombosis Thromb Haemost 88 2002 160 162 (Pubitemid 34752284)
87. N. Akar, R. Gokdemir, D. Ozel, and E. Akar Endothelial cell protein C receptor (EPCR) gene exon III, 23 bp insertion mutation in the Turkish pediatric thrombotic patients Thromb Haemost 88 2002 1068 1069 (Pubitemid 36018799)
88. L. Galligan, W. Livingstone, L. Mynett-Johnston, and O.P. Smith Prevalence of the 23 bp endothelial protein C receptor (EPCR) gene insertion in the Irish population Thromb Haemost 87 2002 773 774 (Pubitemid 34302971)
89. R. Grossmann, S. Schwender, U. Geisen, C. Schambeck, G. Merati, and U. Walter CBS 844ins68, MTHFR TT677 and EPCR 4031ins23 genotypes in patients with deep-vein thrombosis Thromb Res 107 2002 13 15 (Pubitemid 35284420)
90. J. Hermida, V. Hurtado, A. Villegas-Méndez, A.J. Catto, and H. Philippou Identification and characterization of a natural R96C EPCR variant J Thromb Haemost 1 2003 1850 1852
91. N.M. Pecheniuk, D.J. Elias, X. Xu, and J.H. Griffin Failure to validate association of gene polymorphisms in EPCR, PAR-1, FSAP and protein S Tokushima with venous thromboembolism among Californians of European ancestry Thromb Haemost 99 2008 453 455 (Pubitemid 351230981)
92. P. Medina, S. Navarro, A. Estellés, A. Vayá, R.M. Bertina, and F. España Influence of the 4600A/G and 4678G/C polymorphisms in the endothelial protein C receptor (EPCR) gene on the risk of venous thromboembolism in carriers of factor V Leiden Thromb Haemost 94 2005 389 394 (Pubitemid 41122494)
93. F. España, I. Zuazu, V. Vicente, A. Estellés, P. Marco, and J. Aznar Quantification of circulating activated protein C in human plasma by immunoassays-enzyme levels are proportional to total protein C levels Thromb Haemost 75 1996 56 61 (Pubitemid 26051195)
94. F. España, A. Vayá, Y. Mira, P. Medina, A. Estellés, and P. Villa Low level of circulating activated protein C is a risk factor for venous thromboembolism Thromb Haemost 86 2001 1368 1373 (Pubitemid 34007506)
95. J.M. Gu, J.T. Crawley, G. Ferrell, F. Zhang, W. Li, and N.L. Esmon Disruption of the endothelial cell protein C receptor gene in mice causes placental thrombosis and early embryonic lethality J Biol Chem 277 2002 43335 43343 (Pubitemid 35285721)
96. P. Hopmeier, H. Puehringer, M. van Trotsenburg, J. Atamaniuk, C. Oberkanins, and A. Dossenbach-Glaninger Association of endothelial protein C receptor haplotypes, factor V Leiden and recurrent first trimester pregnancy loss Clin Biochem 41 2008 1022 1024
97. M. Kaare, V.M. Ulander, J.N. Painter, T. Ahvenainen, R. Kaaja, and K. Aittomaki Variations in the thrombomodulin and endothelial protein C receptor genes in couples with recurrent miscarriage Hum Reprod 22 2007 864 868
98. P. Medina, F. España, H.L. Vos, and R.M. Bertina Functional analysis of SNPs specific for haplotype 1 (H1) of the gene coding for the Endothelial Protein C Receptor (EPCR) J Thromb Haemost 5 Suppl. 2 2007 P-M-083
99. K. Yamagishi, M. Cushman, S.R. Heckbert, M.Y. Tsai, and A.R. Folsom Lack of association of soluble endothelial protein C receptor and PROCR 6936A/G polymorphism with the risk of venous thromboembolism in a prospective study Br J Haematol 145 2009 221 226
100. P. Simioni, O. Morboeuf, G. Tognin, S. Gavasso, D. Tormene, and B. Woodhams Soluble endothelial protein C receptor (sEPCR) levels and venous thromboembolism in carriers of two dysfunctional protein C variants Thromb Res 117 2006 523 528 (Pubitemid 43326137)
101. S. Navarro, P. Medina, Y. Mira, A. Estellés, P. Villa, and F. Ferrando Haplotypes of the EPCR gene, prothrombin levels, and the risk of venous thrombosis in carriers of the prothrombin G20210A mutation Haematologica 93 2008 885 891 (Pubitemid 351821725)
102. J.P. Galanaud, E. Cochery-Nouvellon, S. Alonso, C. Chauleur, E. Mercier, and G. Lissalde-Lavigne Paternal endothelial protein C receptor 219Gly variant as a mild and limited risk factor for deep vein thrombosis during pregnancy J Thromb Haemost 8 2010 707 713
103. E. Cochery-Nouvellon, C. Chauleur, C. Demattei, E. Mercier, P. Fabbro-Peray, and P. Mares The A6936G polymorphism of the endothelial protein C receptor gene is associated with the risk of unexplained foetal loss in Mediterranean European couples Thromb Haemost 102 2009 656 667
104. G. Lavigne-Lissalde, E. Cochery-Nouvellon, E. Mercier, P. Mares, and J.C. Gris High plasma levels of endothelial protein C receptor are associated with the risk of unexplained fetal death J Thromb Haemost 3 2005 393 395 (Pubitemid 41623634)
105. H. Ireland, C.J. Konstantoulas, J.A. Cooper, E. Hawe, S.E. Humphries, and H. Mather EPCR Ser219Gly: elevated sEPCR, prothrombin F1 + 2, risk for coronary heart disease, and increased sEPCR shedding in vitro Atherosclerosis 183 2005 283 292 (Pubitemid 41579279)
106. D. Qu, Y. Wang, Y. Song, N.L. Esmon, and C.T. Esmon The Ser219- > Gly dimorphism of the endothelial protein C receptor contributes to the higher soluble protein levels observed in individuals with the A3 haplotype J Thromb Haemost 4 2006 229 235
107. A.P. Reiner, C.L. Carty, N.S. Jenny, C. Nievergelt, M. Cushman, and D.J. Stearns-Kurosawa PROC, PROCR and PROS1 polymorphisms, plasma anticoagulant phenotypes, and risk of cardiovascular disease and mortality in older adults: the Cardiovascular Health Study J Thromb Haemost 6 2008 1625 1632
108. W. Tang, S. Basu, X. Kong, J.S. Pankow, N. Aleksic, and A. Tan Genome-wide association study identifies novel loci for plasma levels of protein C: the ARIC study Blood 116 2010 5032 5036
109. H.A. Ireland, J.A. Cooper, F. Drenos, J. Acharya, J.P. Mitchell, and K.A. Bauer FVII, FVIIa, and downstream markers of extrinsic pathway activation differ by EPCR Ser219Gly variant in healthy men Arterioscler Thromb Vasc Biol 29 2009 1968 1974
110. N.L. Smith, M.H. Chen, A. Dehghan, D.P. Strachan, S. Basu, and N. Soranzo Novel associations of multiple genetic loci with plasma levels of factor VII, factor VIII, and von Willebrand factor: The CHARGE (Cohorts for Heart and Aging Research in Genome Epidemiology) Consortium Circulation 121 2010 1382 1392
111. N.S. van de Water, J.K. French, J. McDowell, and P.J. Browett The endothelial protein C receptor (EPCR) 23 bp insert in patients with myocardial infarction Thromb Haemost 85 2001 749 751 (Pubitemid 32293720)
112. P. Medina, S. Navarro, J. Corral, E. Zorio, V. Roldan, and A. Estellés Endothelial protein C receptor polymorphisms and risk of myocardial infarction Haematologica 93 2008 1358 1363
113. A. Ulu, D. Gunal, S. Tiras, Y. Egin, G. Deda, and N. Akar EPCR gene A3 haplotype and elevated soluble endothelial protein C receptor (sEPCR) levels in Turkish pediatric stroke patients Thromb Res 120 2007 47 52 (Pubitemid 46601575)