Vascular PAR-1: Activity and Antagonism

Cardiovascular Therapeutics

Volumn 29, Issue 6, 2011, Pages 349-361

  Lang, Ninian N ^a   Gumundsdóttir, Ingibjörg J ^b   Newby, David E ^a  

^a UNIVERSITY OF EDINBURGH   (United Kingdom)

^b ROYAL INFIRMARY OF EDINBURGH   (United Kingdom)

Author keywords

Antiplatelet agents; Coagulation thrombosis; Lipids disorder atherosclerosis; PAR 1 antagonism

Indexed keywords

ANTITHROMBOCYTIC AGENT; ATOPAXAR; PROTEINASE ACTIVATED RECEPTOR 1; PROTEINASE ACTIVATED RECEPTOR 1 INHIBITOR; RWJ 58259; THROMBIN; THROMBOCYTE ACTIVATING FACTOR; UNCLASSIFIED DRUG; VORAPAXAR;

ATHEROGENESIS; ATHEROSCLEROSIS; CARDIOVASCULAR DISEASE; DRUG ABSORPTION; ENDOTHELIUM; HUMAN; NONHUMAN; PATHOPHYSIOLOGY; PRIORITY JOURNAL; REVIEW; THROMBOSIS; VASCULAR SMOOTH MUSCLE;

ANIMALS; BLOOD VESSELS; CARDIOVASCULAR DISEASES; HEMORRHAGE; HUMANS; PLATELET AGGREGATION INHIBITORS; RECEPTOR, PAR-1; THROMBIN; TREATMENT OUTCOME;

EID: 79955682088     PISSN: 17555914     EISSN: 17555922     Source Type: Journal    
DOI: 10.1111/j.1755-5922.2010.00140.x     Document Type: Review

References (75)

1. Fox KA, Anderson FA, Goodman SG, et al. Time course of events in acute coronary syndromes: Implications for clinical practice from the GRACE registry. Nature Clin Pract Cardiovasc Med 2008;5:580-589.
2. Montalescot G, Dallongeville J, Van Belle E, et al. STEMI and NSTEMI: Are they so different? 1 year outcomes in acute myocardial infarction as defined by the ESC/ACC definition (the OPERA registry). Eur Heart J 2007;28:1409-1417.
3. Davì G, Patrono C. Platelet activation and atherothrombosis. N Engl J Med 2007;357:2482-2494.
4. Jennings LK. Role of platelets in atherothrombosis. Am J Cardiol 2009;103:4A-10A.
5. Mackman N. Triggers, targets and treatments for thrombosis. Nature 2008;451:914-918.
6. Angiolillo DJ. Variability in responsiveness to oral antiplatelet therapy. Am J Cardiol 2009;103:27A-34A.
7. Montalescot G, Wiviott SD, Braunwald E, et al. Prasugrel compared with clopidogrel in patients undergoing percutaneous coronary intervention for ST-elevation myocardial infarction (TRITON-TIMI 38): Double-blind, randomised controlled trial. Lancet 2009;373:723-731.
8. O'Donoghue ML, Braunwald E, Antman EM, et al. Pharmacodynamic effect and clinical efficacy of clopidogrel and prasugrel with or without a proton-pump inhibitor: An analysis of two randomised trials. Lancet 2009;374:989-997.
9. Wallentin L, Becker R, Budaj A, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2009;361:1045-1057.
10. Storey RF, Newby LJ, Heptinstall S. Effects of P2Y(1) and P2Y(12) receptor antagonists on platelet aggregation induced by different agonists in human whole blood. Platelets 2001;12:443-447.
11. Gudmundsdóttir IJ, Megson IL, Kell JS, Ludlam CA, Fox KA, Webb DJ, Newby DE. Direct vascular effects of protease-activated receptor type 1 agonism in vivo in humans. Circulation 2006;114:1625-1632.
12. Sarma J, Laan C, Alam S, Jha A, Fox K, Dransfield I. Increased platelet binding to circulating monocytes in acute coronary syndromes. Circulation 2002;105:2166-2171.
13. Boersma E, Harrington RA, Moliterno DJ, et al. Platelet glycoprotein IIb/IIIa inhibitors in acute coronary syndromes: A meta-analysis of all major randomised clinical trials. Lancet 2002;359:189-198.
14. Investigators SS. Randomized trial of aspirin, sibrafiban, or both for secondary prevention after acute coronary syndromes. Circulation 2001;103:1727-1733.
15. Kereiakes DJ. Oral blockade of the platelet glycoprotein IIb/IIIa receptor: Fact or fancy? Am Heart J 1999;138:S39-S46.
16. Angiolillo DJ, Guzman LA. Clinical overview of promising nonthienopyridine antiplatelet agents. Am Heart J 2008;156:S23-S28.
17. Chackalamannil S. Thrombin receptor (protease activated receptor-1) antagonists as potent antithrombotic agents with strong antiplatelet effects. J Med Chem 2006;49:5389-5403.
18. Chintala M, Shimizu K, Ogawa M, Yamaguchi H, Doi M, Jensen P. Basic and translational research on proteinase-activated receptors: Antagonism of the proteinase-activated receptor 1 for thrombin, a novel approach to antiplatelet therapy for atherothrombotic disease. J Pharmacol Sci 2008;108:433-438.
19. Gross PL, Weitz JI. New antithrombotic drugs. Clin Pharmacol Ther 2009;86:139-146.
20. Jennings LK. Mechanisms of platelet activation: Need for new strategies to protect against platelet-mediated atherothrombosis. Thromb Haemost 2009;102:248-257.
21. Gailani D, Renné T. Intrinsic pathway of coagulation and arterial thrombosis. Arterioscler Thromb Vasc Biol 2007;27:2507-2513.
22. Koenig W. Fibrin(ogen) in cardiovascular disease: An update. Thromb Haemost 2003;89:601-609.
23. Lum H, Malik AB. Regulation of vascular endothelial barrier function. Am J Physiol 1994;267:L223-L241.
24. Croce K, Libby P. Intertwining of thrombosis and inflammation in atherosclerosis. Curr Opin Hematol 2007;14:55-61.
25. Leger A, Covic L, Kuliopulos A. Protease-activated receptors in cardiovascular diseases. Circulation 2006;114:1070-1077.
26. Coughlin S. Protease-activated receptors in hemostasis, thrombosis and vascular biology. J Thromb Haemost 2005;3:1800-1814.
27. Vu T, Hung D, Wheaton V, Coughlin S. Molecular cloning of a functional thrombin receptor reveals a novel proteolytic mechanism of receptor activation. Cell 1991;64:1057-1068.
28. Ossovskaya V, Bunnett N. Protease-activated receptors: Contribution to physiology and disease. Physiol Rev 2004;84:579-621.
29. Hirano K, Kanaide H. Role of protease-activated receptors in the vascular system. J Atheroscler Thromb 2003;10:211-225.
30. Martorell L, Martínez-González J, Rodríguez C, Gentile M, Calvayrac O, Badimon L. Thrombin and protease-activated receptors (PARs) in atherothrombosis. Thromb Haemost 2008;99:305-315.
31. Shapiro MJ, Weiss EJ, Faruqi TR, Coughlin SR. Protease-activated receptors 1 and 4 are shut off with distinct kinetics after activation by thrombin. J Biol Chem 2000;275:25216-25221.
32. Mackie EJ, Loh L-H, Sivagurunathan S, et al. Protease-activated receptors in the musculoskeletal system. Int J Biochem Cell Biol 2008;40:1169-1184.
33. Coughlin S. Thrombin signalling and protease-activated receptors. Nature 2000;407:258-264.
34. Barnes JA, Singh S, Gomes AV. Protease activated receptors in cardiovascular function and disease. Mol Cell Biochem 2004;263:227-239.
35. Scarborough RM, Naughton MA, Teng W, et al. Tethered ligand agonist peptides. Structural requirements for thrombin receptor activation reveal mechanism of proteolytic unmasking of agonist function. J Biol Chem 1992;267:13146-13149.
36. Gudmundsdóttir I, Lang N, Boon N, Ludlam CA, Webb DJ, Fox KA, Newby DE. Role of the endothelium in the vascular effects of the thrombin receptor (protease-activated receptor type 1) in humans. J Am Coll Cardiol 2008;51:1749-1756.
37. Gudmundsdóttir I, Megson I, Kell J, et al. Direct vascular effects of protease-activated receptor type 1 agonism in vivo in humans. Circulation 2006;114:1625-1632.
38. Lang NN, Gudmundsdóttir IJ, Boon NA, Ludlam CA, Fox KA, Newby DE. Marked impairment of protease-activated receptor type 1-mediated vasodilation and fibrinolysis in cigarette smokers: Smoking, thrombin, and vascular responses in vivo. J Am Coll Cardiol 2008;52:33-39.
39. Goto S, Tamura N, Handa S, Arai M, Kodama K, Takayama H. Involvement of glycoprotein VI in platelet thrombus formation on both collagen and von Willebrand factor surfaces under flow conditions. Circulation 2002;106:266-272.
40. Maurice P, Legrand C, Fauvel-Lafeve F. Platelet adhesion and signaling induced by the octapeptide primary binding sequence (KOGEOGPK) from type III collagen. FASEB J 2004;18:1339-1347.
41. Sambrano GR, Weiss EJ, Zheng YW, Huang W, Coughlin SR. Role of thrombin signalling in platelets in haemostasis and thrombosis. Nature 2001;413:74-78.
42. Vandendries ER, Hamilton JR, Coughlin SR, Furie B, Furie BC. Par4 is required for platelet thrombus propagation but not fibrin generation in a mouse model of thrombosis. Proc Natl Acad Sci USA 2007;104:288-292.
43. Weiss EJ, Hamilton JR, Lease KE, Coughlin SR. Protection against thrombosis in mice lacking PAR3. Blood 2002;100:3240-3244.
44. Nelken NA, Soifer SJ, O'Keefe J, Vu TK, Charo IF, Coughlin SR. Thrombin receptor expression in normal and atherosclerotic human arteries. J Clin Invest 1992;90:1614-1621.
45. Patterson C, Stouffer G, Madamanchi N, Runge M. New tricks for old dogs: Nonthrombotic effects of thrombin in vessel wall biology. Circ Res 2001;88:987-997.
46. Minami T, Sugiyama A, Wu S-Q, Abid R, Kodama T, Aird WC. Thrombin and phenotypic modulation of the endothelium. Arterioscler, Thromb, Vasc Biol 2004;24:41-53.
47. Rabiet MJ, Plantier JL, Rival Y, Genoux Y, Lampugnani MG, Dejana E. Thrombin-induced increase in endothelial permeability is associated with changes in cell-to-cell junction organization. Arterioscler, Thromb, Vasc Biol 1996;16:488-496.
48. Wilcox JN, Rodriguez J, Subramanian R, et al. Characterization of thrombin receptor expression during vascular lesion formation. Circ Res 1994;75:1029-1038.
49. Damiano BP, Derian CK, Maryanoff BE, Zhang H-C, Gordon PA. RWJ-58259: A selective antagonist of protease activated receptor-1. Cardiovasc Drug Rev 2003;21:313-326.
50. Maragoudakis ME, Kraniti N, Giannopoulou E, Alexopoulos K, Matsoukas J. Modulation of angiogenesis and progelatinase a by thrombin receptor mimetics and antagonists. Endothelium 2001;8:195-205.
51. McNamara CA, Sarembock IJ, Gimple LW, Fenton JW, Coughlin SR, Owens GK. Thrombin stimulates proliferation of cultured rat aortic smooth muscle cells by a proteolytically activated receptor. J Clin Invest 1993;91:94-98.
52. Takada M, Tanaka H, Yamada T, et al. Antibody to thrombin receptor inhibits neointimal smooth muscle cell accumulation without causing inhibition of platelet aggregation or altering hemostatic parameters after angioplasty in rat. Circ Res 1998;82:980-987.
53. Cheung WM, D'Andrea MR, Andrade-Gordon P, Damiano BP. Altered vascular injury responses in mice deficient in protease-activated receptor-1. Arterioscler, Thromb, Vasc Biol 1999;19:3014-3024.
54. Kawabata A, Kubo S, Nakaya Y, et al. Distinct roles for protease-activated receptors 1 and 2 in vasomotor modulation in rat superior mesenteric artery. Cardiovasc Res 2004;61:683-692.
55. Kawabata A, Nakaya Y, Ishiki T, et al. Receptor-activating peptides for PAR-1 and PAR-2 relax rat gastric artery via multiple mechanisms. Life Sci 2004;75:2689-2702.
56. Hamilton JR, Nguyen PB, Cocks TM. Atypical protease-activated receptor mediates endothelium-dependent relaxation of human coronary arteries. Circ Res 1998;82:1306-1311.
57. Hamilton JR, Moffatt JD, Frauman AG, Cocks TM. Protease-activated receptor (PAR) 1 but not PAR2 or PAR4 mediates endothelium-dependent relaxation to thrombin and trypsin in human pulmonary arteries. J Cardiovasc Pharmacol 2001;38:108-119.
58. Sicker T, Wuchold F, Kaiser B, Glusa E. Systemic vascular effects of thrombin and thrombin receptor activating peptide in rats. Thromb Res 2001;101:467-475.
59. Gudmundsdóttir IJ, Lang NN, Boon NA, et al. Role of the endothelium in the vascular effects of the thrombin receptor (protease-activated receptor type 1) in humans. J Am Coll Cardiol 2008;51:1749-1756.
60. Ku DD, Zaleski JK. Receptor mechanism of thrombin-induced endothelium-dependent and endothelium-independent coronary vascular effects in dogs. J Cardiovasc Pharmacol 1993;22:609-616.
61. Ku DD, Dai J. Expression of thrombin receptors in human atherosclerotic coronary arteries leads to an exaggerated vasoconstrictory response in vitro. J Cardiovasc Pharmacol 1997;30:649-657.
62. Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009;361:1139-1151.
63. Derian CK, Damiano BP, Addo MF, et al. Blockade of the thrombin receptor protease-activated receptor-1 with a small-molecule antagonist prevents thrombus formation and vascular occlusion in nonhuman primates. J Pharmacol Exp Ther 2003;304:855-861.
64. Cook JJ, Sitko GR, Bednar B, et al. An antibody against the exosite of the cloned thrombin receptor inhibits experimental arterial thrombosis in the African green monkey. Circulation 1995;91:2961-2971.
65. Becker RC, Moliterno DJ, Jennings LK, et al. Safety and tolerability of SCH 530348 in patients undergoing non-urgent percutaneous coronary intervention: A randomised, double-blind, placebo-controlled phase II study. Lancet 2009;373:919-928.
66. Brass LF, Vassallo RR, Belmonte E, Ahuja M, Cichowski K, Hoxie JA. Structure and function of the human platelet thrombin receptor. Studies using monoclonal antibodies directed against a defined domain within the receptor N terminus. J Biol Chem 1992;267:13795-13798.
67. Andrade-Gordon P, Maryanoff BE, Derian CK, et al. Design, synthesis, and biological characterization of a peptide-mimetic antagonist for a tethered-ligand receptor. Proc Natl Acad Sci USA 1999;96:12257-12262.
68. Andrade-Gordon P, Derian CK, Maryanoff BE, et al. Administration of a potent antagonist of protease-activated receptor-1 (PAR-1) attenuates vascular restenosis following balloon angioplasty in rats. J Pharmacol Exp Ther 2001;298:34-42.
69. Covic L, Misra M, Badar J, Singh C, Kuliopulos A. Pepducin-based intervention of thrombin-receptor signaling and systemic platelet activation. Nat Med 2002;8:1161-1165.
70. Shah R. Protease-activated receptors in cardiovascular health and diseases. Am Heart J 2009;157:253-262.
71. Leger AJ, Jacques SL, Badar J, et al. Blocking the protease-activated receptor 1-4 heterodimer in platelet-mediated thrombosis. Circulation 2006;113:1244-1254.
72. Husted S. New developments in oral antiplatelet therapy. Eur Heart J Suppl 2007;9:D20-D27.
73. Chackalamannil S, Wang Y, Greenlee WJ, et al. Discovery of a novel, orally active himbacine-based thrombin receptor antagonist (SCH 530348) with potent antiplatelet activity. J Med Chem 2008;51:3061-3064.
74. Oliver JJ, Webb DJ, Newby DE. Stimulated tissue plasminogen activator release as a marker of endothelial function in humans. Arterioscler Thromb Vasc Biol 2005;25:2470-2479.
75. Robinson SD, Ludlam CA, Boon NA, Newby DE. Endothelial fibrinolytic capacity predicts future adverse cardiovascular events in patients with coronary heart disease. Arterioscler Thromb Vasc Biol 2007;27:1651-1656.