Activated protein C: An emerging therapeutic agent in the prevention of ischemia-reperfusion injury

Journal of Reconstructive Microsurgery

Volumn 24, Issue 5, 2008, Pages 361-367

  Bezuhly, Michael ^a   Liwski, Robert ^a   West, Kenneth A ^a   Morris, Steven F ^a  

^a DALHOUSIE UNIVERSITY   (Canada)

Author keywords

Activated protein C; Flap failure; Reperfusion injury

Indexed keywords

ACTIVATED PROTEIN C; ANTICOAGULANT AGENT; HEPARIN;

ANTICOAGULATION; ANTIINFLAMMATORY ACTIVITY; APOPTOSIS; BLOOD VESSEL PERMEABILITY; CELL INTERACTION; DRUG MECHANISM; ENDOTHELIUM CELL; FIBRINOLYSIS; FREE TISSUE GRAFT; HUMAN; IN VIVO STUDY; INFLAMMATION; ISCHEMIA; LEUKOCYTE; MICROVASCULAR SURGERY; NONHUMAN; PRIORITY JOURNAL; REPERFUSION INJURY; REVIEW; THROMBOCYTE;

ANIMALS; APOPTOSIS; GRAFT SURVIVAL; HUMANS; PROTEIN C; REPERFUSION INJURY; SURGICAL FLAPS;

EID: 48649094566     PISSN: 0743684X     EISSN: None     Source Type: Journal    
DOI: 10.1055/s-2008-1080540     Document Type: Review

References (90)

1. Morris SF, Pang CY, Zheng A, Boyd B, Forrest CR. Assessment of ischemia-induced reperfusion injury in the pig latissimus dorsi myocutaneous flap model. Plast Reconstr Surg 1993;92:1162-1172
2. Siemionow M, Arslan E. Ischemia/reperfusion injury: a review in relation to free tissue transfers. Microsurgery 2004;24:468-475
3. Grace PA. Ischaemia-reperfusion injury. Br J Surg 1994;81:637-647
4. Zimmerman BJ, Granger DN. Mechanisms of reperfusion injury. Am J Med Sci 1994;307:284-292
5. Goswami SK, Maulik N, Das DK. Ischemia-reperfusion and cardioprotection: a delicate balance between reactive oxygen species generation and redox homeostasis. Ann Med 2007;39:275-289
6. Huang L, Privalle CT, Serafin D, Klitzman B. Increased survival of skin flaps by scavengers of superoxide radicals. FASEB J 1987;1:129-132
7. Kim YS, Im MJ, Hoopes JE. The effect of a free-radical scavenger, N-2-mercaptopropionylglycine, on the survival of skin flaps. Ann Plast Surg 1990;25:18-20
8. De Greef KE, Ysebaert DK, Ghielli M, et al. Neutrophils and acute ischemia-reperfusion injury. J Nephrol 1998;11:110-122
9. Hossain MA, Wakabayashi H, Izuishi K, et al. The role of prostaglandins in liver ischemia-reperfusion injury. Curr Pharm Des 2006;12:2935-2951
10. Oredsson S, Plate G, Qvarfordt P. Experimental evaluation of oxygen radical scavengers in the prevention of reperfusion injury in skeletal muscle. Eur J Surg 1994;160:97-103
11. Ogawa S, Gerlach H, Esposito C, Pasagian-Macaulay A, Brett J, Stern D. Hypoxia modulates the barrier and coagulant function of cultured bovine endothelium: increased monolayer permeability and induction of procoagulant properties. J Clin Invest 1990;85:1090-1098
12. Davies MG, Hagen PO. The vascular endothelium. A new horizon. Ann Surg 1993;218:593-609
13. Rubanyi GM, Polokoff MA. Endothelins: molecular biology, biochemistry, pharmacology, physiology, and pathophysiology. Pharmacol Rev 1994;46:325-415
14. Barnes PJ. Nuclear factor-κB. Int J Biochem Cell Biol 1997;29:867-870
15. Toledo-Pereyra LH, Toledo AH, Walsh K, Lopez-Neblina F. Molecular signaling pathways in ischemia/reperfusion. Exp Clin Transplant 2004;2:174-177
16. 1 integrin expression and function. Atherosclerosis 2001;154:377-385
17. Frangogiannis NG. Chemokines in ischemia and reperfusion. Thromb Haemost 2007;97:738-747
18. Ambrosio G, Tritto I. Reperfusion injury: experimental evidence and clinical implications. Am Heart J 1999;138:S69-75
19. Nishijima K, Kiryu J, Tsujikawa A, et al. In vivo evaluation of platelet-endothelial interactions after transient retinal ischemia. Invest Ophthalmol Vis Sci 2001;42:2102-2109
20. Okada Y, Marchevesky A, Zuo X, et al. Accumulation of platelets in rat syngeneic lung transplants. Transplantation 1997;64:801-806
21. Roberts AM, Ovechkin AV, Mowbray JG, Robinson TW, Lominadze D. Effects of pulmonary ischemia-reperfusion on platelet adhesion in subpleural arterioles in rabbits. Microvasc Res 2004;67:29-37
22. Piccardoni P, Evangelista V, Piccoli A, de Gaetano G, Walz A, Cerletti C. Thrombin activated human platelets release two NAP 2 variants that stimulate polymorphonuclear leukocytes. Thromb Haemost 1996;76:780-785
23. Carvalho-Tavares J, Hickey MJ, Hutchison J, Michaud J, Sutcliffe IT, Kubes P. A role for platelets and endothelial selectins in tumor necrosis factor-alpha-induced leukocyte recruitment in the brain microvasculature. Circ Res 2000;87:1141-1148
24. Faint RW. Platelet-neutrophil interactions: their significance. Blood Rev 1992;6:83-91
25. Frenette PS, Moyna C, Hartwell DW, Lowe JB, Hynes RO, Wagner DD. Platelet-endothelial interactions in inflamed mesentric venules. Blood 1998;91:1318-1324
26. Ruf A, Patscheke H. Platelet-induced neutrophil activation: platelet-expressed fibrinogen induces the oxidative burst in neutrophils by an interaction with CD11C/CD18. Br J Haematol 1995;90:791-796
27. Carden DL, Granger DN. Pathophysiology of ischaemia-reperfusion injury. J Pathol 2000;190:255-266
28. Cooper D, Chitman KD, Williams MC, Granger DN. Time-dependent platelet-vessel wall interactions induced by intestinal ischemia-reperfusion. Am J Physiol Gastrointest Liver Physiol 2003;284:G1027-G1033
29. Minamino T, Kitakaze M, Sanada S, et al. Increased expression of P-selectin on platelets is a risk factor for silent cerebral infarction in patients with atrial fibrillation: role of nitric oxide. Circulation 1998;98:1721-1727
30. Blann AD, Nadar SK, Lip GY. The adhesion molecule P-selectin and cardiovascular disease. Eur Heart J 2003;24:2 166-2179
31. Dardik R, Shenkman B, Tamarin I. Factor XIII mediates adhesion of platelets to endothelial cells through alpha(v) beta(3) and glycoprotein IIb/IIIa integrins. Thromb Res 2002;105:317-323
32. Petruzzelli L, Takami M, Humes H. Structure and function of cell adhesion molecules. Am J Med 1999;106:467-476
33. Schurmann G. Cell adhesion: molecular principles and initial implications for surgery. Chirurg 1997;68:477-487
34. Jung U, Ley K. Regulation of E-selectin, P-selectin, and intercellular adhesion molecule 1 expression in mouse cremaster muscle vasculature. Microcirculation 1997;4:311-319
35. Khandoga A, Biberthaler P, Enders G, et al. Platelet adhesion mediated by fibrinogen-intercellular adhesion molecule-1 binding induces tissue injury in the postischemic liver in vivo. Transplantation 2002;74:681-688
36. Love S, Barber R. Expression of P-selectin and intracellular adhesion molecule-1 in human brain after focal infarction or cardiac arrest. Neuropathol Appl Neurobiol 2001;27:465-473
37. Perrot M, Liu M, Waddell T, Keshavjee S. Ischemia-reperfusion-induced lung injury. Am J Respir Crit Care Med 2003;167:490-511
38. Haug CE, Colvin RB, Delmonico FL, et al. A phase I trial of immunosuppression with anti-ICAM-1 (CD54) MAb in renal allograft recipients. Transplantation 1993;55:766-772
39. Merchant SH, Gurule DM, Larson RS. Amelioration of ischemia-reperfusion injury with cyclic peptide blockade of ICAM-1. Am J Physiol Heart Circ Physiol 2003;284:H1260-H1268
40. Demirseren ME, Sarici M, Gokrem S, Yenidunya S. Protective effects of monoclonal antibody to intercellular adhesion molecule-1 in venous ischemia-reperfusion injury: experimental study in rats. J Reconstr Microsurg 2007;23:41-44
41. Harris NR, Granger ND. Ischemia/reperfusion injury. In: Toledo-Pereyra LH, ed. Organ Procurements and Preservation for Transplantation, 2nd ed. Heidelberg: Springer-Verlag; 1997:67-81
42. Carden DL, Smith JK, Korthuis RJ. Neutrophil-mediated microvascular dysfunction in postischemic canine skeletal muscle. Role of granulocyte adherence. Circ Res 1990;66:1436-1444
43. Kerrigan CL, Stotland MA. Ischemia reperfusion injury: a review. Microsurgery 1993;14:165-175
44. Vinten-Johansen J. Involvement of neutrophils in the pathogenesis of lethal myocardial reperfusion injury. Cardiovasc Res 2004;61:481-497
45. Stempien-Otero A, Karsan A, Cornejo CJ, et al. Mechanisms of hypoxia-induced endothelial cell death. Role of p53 in apoptosis. J Biol Chem 1999;274:8039-8045
46. Matsushita H, Morishita R, Nata T, et al. Hypoxia-induced endothelial apoptosis through nuclear factor-kappaB (NF-kappaB)-mediated Bcl-2 suppression: in vivo evidence of the importance of NF-kappaB in endothelial cell regulation. Circ Res 2000;86:974-981
47. Walford GA, Moussignac RL, Scribner AW, Loscalzo J, Leopold JA. Hypoxia potentiates nitric oxide-mediated apoptosis in endothelial cells via peroxynitrite-induced activation of mitochondria-dependent and -independent pathways. J Biol Chem 2004;279:4425-4432
48. Lopez-Neblina F, Toledo AH, Toledo-Pereyra LH. Molecular biology of apoptosis in ischemia and reperfusion. J Invest Surg 2005;18:335-350
49. Scarabelli TM, Stephanou A, Pasini E, et al. Different signaling pathways induce apoptosis in endothelial cells and cardiac myocytes during ischemia/reperfusion injury. Circ Res 2002;90:745-748
50. Kohli V, Selzner M, Madden JF, Bentley RC, Clavien PA. Endothelial cell and hepatocyte deaths occur by apoptosis after ischemia-reperfusion injury in the rat liver. Transplantation 1999;67:1099-1105
51. Scarabelli T, Stephanou A, Rayment N, et al. Apoptosis of endothelial cells precedes myocyte cell apoptosis in ischemia/reperfusion injury. Circulation 2001;104:253-256
52. Iwata A, Harlan JM, Vedder NB, Winn RK. The caspase inhibitor z-VAD is more effective than CD18 adhesion blockade in reducing muscle ischemia-reperfusion injury: implication for clinical trials. Blood 2002;100:2077-2080
53. Griffin JH, Evatt B, Zimmerman TS, Kleiss AJ, Wideman C. Deficiency of protein C in congenital thrombotic disease. J Clin Invest 1981;68:1370-1373
54. Branson HE, Katz J, Marble R, Griffin JH. Inherited protein C deficiency and coumarin-responsive chronic relapsing purpura fulminans in a newborn infant. Lancet 1983;2:1165-1168
55. Bernard GR, Vincent JL, Laterre PF, et al. Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med 2001;344:699-709
56. Abraham E, Reinhart K, Opal S, et al. Efficacy and safety of tifacogin (recombinant tissue factor pathway inhibitor) in severe sepsis: a randomized controlled trial. JAMA 2003;290:238-247
57. Warren BL, Eid A, Singer P, et al. High-dose antithrombin III in severe sepsis: a randomized controlled trial. JAMA 2001;286:1869-1878
58. Kerschen EJ, Fernandez JA, Cooley BC, et al. Endotoxemia and sepsis mortality reduction by non-coagulant activated protein C. J Exp Med 2007;204:2439-2448
59. Gruber A, Griffin JH. Direct detection of activated protein C in blood from human subjects. Blood 1992;79:2340-2348
60. Esmon C. The protein C pathway. Crit Care Med 2000;28(suppl):S44-S48
61. Stearns-Kurosawa DJ, Kurosawa S, Mollica JS, Ferrell GL, Esmon CT. The endothelial cell protein C receptor augments protein C activation by the thrombin-thrombomodulin complex. Proc Natl Acad Sci U S A 1996;93:10212-10216
62. Bae JS, Yang L, Rezaie AR. Receptors of the protein C activation and activated protein C signaling pathways are colocalized in lipid rafts on endothelial cells. Proc Natl Acad Sci U S A 2007;104:2867-2877
63. Looney MR, Matthay MA. Bench-to-bedside review: the role of activated protein C in maintaining endothelial tight junction function and its relationship to organ injury. Crit Care 2006;10:239-244
64. Esmon CT. The protein C pathway. Chest 2003;124:26S-32S
65. Vu TK, Hung DT, Wheaton VI, Coughlin SR. Molecular cloning of a functional thrombin receptor reveals a novel proteolytic mechanism of receptor activation. Cell 1991;64:1057-1068
66. Joyce DE, Gelbert L, Ciaccia A, DeHoff B, Grinnell BW. Gene expression profile of antithrombotic protein C defines new mechanisms modulating inflammation and apoptosis. J Biol Chem 2001;276:11199-11203
67. Domotor E, Benzakour O, Griffin JH, et al. Activated protein C alters cytosolic calcium flux in human brain endothelium via binding to endothelial protein C receptor and activation of protease activated receptor-1. Blood 2003;101:4797-4801
68. Riewald M, Petrovan RJ, Donner A, Mueller BM, Ruf W. Activation of endothelial cell protease activated receptor 1 by the protein C pathway. Science 2002;296:1880-1882
69. Cheng T, Liu D, Griffin JH, et al. Activated protein C blocks p53-mediated apoptosis in ischemic human brain endothelium and is neuroprotective. Nat Med 2003;9:338-342
70. Mosnier LO, Griffin JH. Inhibition of staurosporine-induced apoptosis of endothelial cells by activated protein C requires protease activated receptor-1 and endothelial cell protein C receptor. Biochem J 2003;373:65-70
71. Joyce DE, Grinnell BW. Recombinant human activated protein C attenuates the inflammatory response in endothelium and monocytes by modulating nuclear factor-kappaB. Crit Care Med 2002;30:S288-S293
72. Franscini N, Bachli EB, Blau N, et al. Gene expression profiling of inflamed human endothelial cells and influence of activated protein C. Circulation 2004;110:2903-2909
73. Hoffmann JN, Vollmar B, Laschke MW, et al. Micro-circulatory alterations in ischemia-reperfusion injury and sepsis: effects of activated protein C and thrombin inhibition. Crit Care 2005;9:S33-S37
74. Gupta A, Rhodes GJ, Berg DT, et al. Activated protein C ameliorates LPS-induced acute kidney injury and down-regulates renal INOS and angiotensin 2. Am J Physiol Renal Physiol 2007;293:F245-F254
75. Bartolome S, Wood JG, Casillan AJ, Simpson SQ, O'Brien-Ladner AR. Activated protein C attenuates microvascular injury during systemic hypoxia. Shock 2008;29:384-387
76. McVerry BJ, Garcia JG. Endothelial cell barrier regulation by sphingosine 1-phosphate. J Cell Biochem 2004;92:1075-1085
77. Singleton PA, Dudek SM, Chiang ET, Garcia JG. Regulation of sphingosine 1-phosphate-induced endothelial cytoskeletal rearrangement and barrier enhancement by S1P1 receptor, PI3 kinase, Tiam1/Rac1, and alpha-actinin. FASEB J 2005;19:1646-1656
78. Bae JS, Yang L, Manithody C, Rezaie AR. The ligand occupancy of endothelial protein C receptor switches the PAR-1-dependent signaling specificity of thrombin from a permeability-enhancing to barrier-protective response in endothelial cells. Blood 2007;110:3909-3916
79. Feistritzer C, Sturn DH, Kaneider NC, Djanani A, Wiedermann CJ. Endothelial protein C receptor-dependent inhibition of human eosinophil chemotaxis by protein C. J Allergy Clin Immunol 2003;112:375-381
80. Galligan L, Livingstone W, Volkov Y, et al. Characterization of protein C receptor expression in monocytes. Br J Haematol 2001;115:408-414
81. Sturn DH, Kaneider NC, Feistritzer C, et al. Expression and function of the endothelial protein C receptor in human neutrophils. Blood 2003;102:1499-1505
82. Joyce DE, Nelson DR, Grinnell BW. Leukocyte and endothelial cell interactions in sepsis: relevance of the protein C pathway. Crit Care Med 2004;32:S280-S286
83. Kurosawa S, Esmon CT, Stearns-Kurosawa DJ. The soluble endothelial protein C receptor binds to activated neutrophils: involvement of proteinase-3 and CD11b/CD18. J Immunol 2000;165:4697-4703
84. Murakami K, Okajima K, Uchiba M, et al. Activated protein C attenuates endotoxin-induced pulmonary vascular injury by inhibiting activated leukocytes in rats. Blood 1996;87:642-647
85. Taoka Y, Okajima K, Uchiba M, et al. Activated protein C reduces the severity of compression-induced spinal cord injury in rats by inhibiting activation of leukocytes. J Neurosci 1998;18:1393-1398
86. Liu D, Cheng T, Guo H, et al. Tissue plasminogen activator neurovascular toxicity is controlled by activated protein C. Nat Med 2004;10:1379-1383
87. Yamaguchi Y, Hisama N, Okajima K, et al. Pretreatment with activated protein C or active human urinary thrombo-modulin attenuates the production of cytokine-induced neutrophil chemoattractant following ischemia/reperfusion in rat liver. Hepatology 1997;25:1136-1140
88. Mizutani A, Okajima K, Uchiba M, Noguchi T. Activated protein C reduces ischemia/reperfusion-induced renal injury in rats by inhibiting leukocyte activation. Blood 2000;95:3781-3787
89. Schoots IG, Levi M, van Vliet AK, Maas AM, Roossink EH, van Gulik TM. Inhibition of coagulation and inflammation by activated protein C or antithrombin reduces intestinal ischemia/reperfusion injury in rats. Crit Care Med 2004;32:1375-1383
90. Dillon JP, Laing AJ, Cahill RA, et al. Activated protein C attenuates acute ischaemia reperfusion injury in skeletal muscle. J Orthop Res 2005;23:1454-1459