Future innovations in anti-platelet therapies

British Journal of Pharmacology

Volumn 154, Issue 5, 2008, Pages 918-939

  Barrett, N E ^a   Holbrook, L ^a   Jones, S ^a,b   Kaiser, W J ^a   Moraes, L A ^a   Rana, R ^a   Sage, T ^a   Stanley, R G ^a   Tucker, K L ^a   Wright, B ^a   Gibbins, J M ^a  

^a UNIVERSITY OF READING   (United Kingdom)

^b NATIONAL HEART AND LUNG INSTITUTE   (United Kingdom)

Author keywords

Anti platelet therapies; Cardiovascular disease; Haemostasis; Platelets; Thrombosis

Indexed keywords

ABCIXIMAB; ACETYLSALICYLIC ACID; ANTITHROMBOCYTIC AGENT; ANTIVITAMIN K; BERAPROST; CD31 ANTIGEN; CD40 ANTIGEN; CILOSTAZOL; CLOPIDOGREL; DIPYRIDAMOLE; DRUG RECEPTOR; E 5555; EPHRIN; EPTIFIBATIDE; G PROTEIN COUPLED RECEPTOR; GLYCOPROTEIN 1B ANTAGONIST; HEPARIN; ILOPROST; INTEGRIN RECEPTOR; PRASUGREL; PROSTACYCLIN; SCH 530348; SCH 53048; SEMAPHORIN; TACHYKININ; TACHYKININ RECEPTOR ANTAGONIST; THROMBIN INHIBITOR; THROMBOXANE A2; TICAGRELOR; TICLOPIDINE; TIROFIBAN;

BLEEDING; BLEEDING TIME; BLOOD CLOTTING; CARDIOVASCULAR DISEASE; CLINICAL TRIAL; DOSE RESPONSE; DRUG MECHANISM; DRUG MEGADOSE; GASTROINTESTINAL SYMPTOM; GENE DELETION; HEART DISEASE; HEART INFARCTION; HUMAN; KIDNEY FAILURE; NEUTROPENIA; NONHUMAN; PRIORITY JOURNAL; REVIEW; SIDE EFFECT; SIGNAL TRANSDUCTION; STOMACH IRRITATION; STOMACH ULCER; STROKE; THROMBOCYTE FUNCTION; THROMBOSIS; THROMBOTIC THROMBOCYTOPENIC PURPURA; UNSPECIFIED SIDE EFFECT;

ANIMALS; BLOOD PLATELETS; CARDIOVASCULAR DISEASES; DRUG DESIGN; DRUGS, INVESTIGATIONAL; FIBRINOLYTIC AGENTS; HEMOSTASIS; HUMANS; PLATELET AGGREGATION INHIBITORS; SIGNAL TRANSDUCTION; THROMBOSIS;

EID: 46249128327     PISSN: 00071188     EISSN: 14765381     Source Type: Journal    
DOI: 10.1038/bjp.2008.151     Document Type: Review

References (272)

1. Abi-Younes S, Si-Tahar M, Luster AD (2001). The CC chemokines MDC and TARC induce platelet activation via CCR4. Thromb Res 101: 279-289.
2. Ahamed J, Versteeg HH, Kerver M, Chen VM, Mueller BM, Hogg PJ et al. (2006). Disulfide isomerization switches tissue factor from coagulation to cell signaling. Proc Natl Acad Sci USA 103: 13932-13937.
3. Akbiyik F, Ray DM, Gettings KF, Blumberg N, Francis CW, Phipps RP (2004). Human bone marrow megakaryocytes and platelets express PPARgamma, and PPARgamma agonists blunt platelet release of CD40 ligand and thromboxanes. Blood 104: 1361-1368.
4. Albelda SM, Oliver PD, Romer LH, Buck CA (1990). EndoCAM: a novel endothelial cell-cell adhesion molecule. J Cell Biol 110: 1227-1237.
5. Ali FY, Davidson SJ, Moraes LA, Traves SL, Paul-Clark M, Bishop-Bailey D et al. (2006). Role of nuclear receptor signaling in platelets: antithrombotic effects of PPARbeta. FASEB J 20: 326-328.
6. Anderson KE, Jackson SP (2003). Class I phosphoinositide 3-kinases. Int J Biochem Cell Biol 35: 1028-1033.
7. Andre P, Delaney SM, LaRocca T, Vincent D, DeGuzman F, Jurek M et al. (2003). P2Y12 regulates platelet adhesion/activation, thrombus growth, and thrombus stability in injured arteries. J Clin Invest 112: 398-406.
8. Andre P, Prasad KS, Denis CV, He M, Papalia JM, Hynes RO et al. (2002). CD40L stabilizes arterial thrombi by a beta3 integrin-dependent mechanism. Nat Med 8: 247-252.
9. Andrews RK, Berndt MC (2004). Platelet physiology and thrombosis. Thromb Res 114: 447-453.
10. Angelillo-Scherrer A, Burnier L, Flores N, Savi P, DeMol M, Schaeffer P et al. (2005). Role of Gas6 receptors in platelet signaling during thrombus stabilization and implications for antithrombotic therapy. J Clin Invest 115: 237-246.
11. Angelillo-Scherrer A, de Frutos P, Aparicio C, Melis E, Savi P, Lupu F et al. (2001). Deficiency or inhibition of Gas6 causes platelet dysfunction and protects mice against thrombosis. Nat Med 7: 215-221.
12. Antipenko A, Himanen JP, van Leyen K, Nardi-Dei V, Lesniak J, Barton WA et al. (2003). Structure of the semaphorin-3A receptor binding module. Neuron 39: 589-598.
13. Antithrombotic Trialists' Collaboration (2002). Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ 324: 71-86.
14. Armstrong RA (1996). Platelet prostanoid receptors. Pharmacol Ther 72: 171-191.
15. Aukrust P, Yndestad A, Smith C, Ueland T, Gullestad L, Damas JK (2007). Chemokines in cardiovascular risk prediction. Thromb Haemost 97: 748-754.
16. Awtry EH, Loscalzo J (2000). Aspirin. Circulation 101: 1206-1218.
17. Balogh I, Hafizi S, Stenhoff J, Hansson K, Dahlback B (2005). Analysis of Gas6 in human platelets and plasma. Arterioscler Thromb Vasc Biol 25: 1280-1286.
18. Barrow AD, Astoul E, Floto A, Brooke G, Relou IA, Jennings NS et al. (2004). Cutting edge: TREM-like transcript-1, a platelet immunoreceptor tyrosine-based inhibition motif encoding costimulatory immunoreceptor that enhances, rather than inhibits, calcium signaling via SHP-2. J Immunol 172: 5838-5842.
19. Basile JR, Barac A, Zhu TQ, Guan KL, Gutkind JS (2004). Class IV semaphorins promote angiogenesis by stimulating Rho-initiated pathways through plexin-B. Cancer Res 64: 5212-5224.
20. Becker RW, Lusis E, Sohn RL, Kline RA (2005). Effects of cilostazol on human venous smooth muscle. Ann Vasc Surg 19: 393-397.
21. Bennett CL, Connors JM, Carwile JM, Moake JL, Bell WR, Tarantolo SR et al. (2000). Thrombotic thrombocytopenic purpura associated with clopidogrel. N Engl J Med 342: 1773-1777.
22. Berger JP, Akiyama TE, Meinke PT (2005). PPARs: therapeutic targets for metabolic disease. Trends Pharmacol Sci 26: 244-251.
23. Bergmeier W, Goerge T, Wang HW, Crittenden JR, Baldwin AC, Cifuni SM et al. (2007). Mice lacking the signaling molecule CalDAG-GEFI represent a model for leukocyte adhesion deficiency type III. J Clin Invest 117: 1699-1707.
24. Bergmeier W, Piffath CL, Goerge T, Cifuni SM, Ruggeri ZM, Ware J et al. (2006). The role of platelet adhesion receptor GPIbalpha far exceeds that of its main ligand, von Willebrand factor, in arterial thrombosis. Proc Natl Acad Sci USA 103: 16900-16905.
25. Bhatt DL, Topol EJ (2000). Current role of platelet glycoprotein IIb/IIIa inhibitors in acute coronary syndromes. JAMA 284: 1549-1558.
26. Bhatt DL, Topol EJ (2003). Scientific and therapeutic advances in antiplatelet therapy. Nat Rev Drug Discov 2: 15-28.
27. Brass LF, Jiang H, Wu J, Stalker TJ, Zhu L (2006). Contact-dependent signaling events that promote thrombus formation. Blood Cells Mol Dis 36: 157-161.
28. British Heart Foundation (2006) heartstat.org.
29. Buckley CD, Doyonnas R, Newton JP, Blystone SD, Brown EJ, Watt SM et al. (1996). Identification of avb3 as a heterotypic ligand for CD31/PECAM-1. J Cell Sci 109: 437-445.
30. Cairns JA, Gent M, Singer J, Finnie KJ, Froggatt GM, Holder DA et al. (1985). Aspirin, sulfinpyrazone, or both in unstable angina - results of a Canadian Multicenter Trial. N Engl J Med 313: 1369-1375.
31. Callow AD (2006). Cardiovascular disease 2005 - the global picture. Vascul Pharmacol 45: 302-307.
32. CAPRIE Steering Committee (1996). A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). CAPRIE Steering Committee. Lancet 348: 1329-1339.
33. Casserly IP, Topol EJ (2002). Glycoprotein IIb/IIIa antagonists - from bench to practice. Cell Mol Life Sci 59: 478-500.
34. Cauwenberghs N, Meiring M, Vauterin S, van Wyk V, Lamprecht S, Roodt JP et al. (2000). Antithrombotic effect of platelet glycoprotein Ib-blocking monoclonal antibody Fab fragments in nonhuman primates. Arterioscler Thromb Vasc Biol 20: 1347-1353.
35. Chakrabarti S, Blair P, Freedman JE (2007). CD40-40L signaling in vascular inflammation. J Biol Chem 282: 18307-18317.
36. Chan B, Lanyi A, Song HK, Griesbach J, Simarro-Grande M, Poy F et al. (2003). SAP couples Fyn to SLAM immune receptors. Nat Cell Biol 5: 155-160.
37. Chen C, Li Q, Darrow AL, Wang Y, Derian CK, Yang J et al. (2004a). Mer receptor tyrosine kinase signaling participates in platelet function. Arterioscler Thromb Vasc Biol 24: 1118-1123.
38. Chen J, De S, Damron DS, Chen WS, Hay N, Byzova TV (2004b). Impaired platelet responses to thrombin and collagen in AKT-1-deficient mice. Blood 104: 1703-1710.
39. Chen J, Diacovo TG, Grenache DG, Santoro SA, Zutter MM (2002). The alpha(2) integrin subunit-deficient mouse: a multifaceted phenotype including defects of branching morphogenesis and hemostasis. Am J Pathol 161: 337-344.
40. Chen K, Detwiler TC, Essex DW (1995). Characterization of protein disulphide isomerase released from activated platelets. Br J Haematol 90: 425-431.
41. Chen K, Lin Y, Detwiler TC (1992). Protein disulfide isomerase activity is released by activated platelets. Blood 79: 2226-2228.
42. Chen VM, Hogg PJ (2006). Allosteric disulfide bonds in thrombosis and thrombolysis. J Thromb Haemost 4: 2533-2541.
43. Chew DP (2001). Oral glycoprotein IIb/IIIa antagonists in coronary artery disease. Curr Cardiol Rep 3: 63-71.
44. Chew DP, Bhatt DL, Sapp S, Topol EJ (2001). Increased mortality with oral platelet glycoprotein IIb/IIIa antagonists: a meta-analysis of phase III multicenter randomized trials. Circulation 103: 201-206.
45. Chou J, Mackman N, Merrill-Skoloff G, Pedersen B, Furie BC, Furie B (2004). Hematopoietic cell-derived microparticle tissue factor contributes to fibrin formation during thrombus propagation. Blood 104: 3190-3197.
46. Chrzanowska-Wodnicka M, Smyth SS, Schoenwaelder SM, Fischer TH, White II GC (2005). Rap1b is required for normal platelet function and hemostasis in mice. J Clin Invest 115: 680-687.
47. Cicmil M, Thomas JM, Leduc M, Bon C, Gibbins JM (2002). Platelet endothelial cell adhesion molecule-1 signaling inhibits the activation of human platelets. Blood 99: 137-144.
48. Cicmil M, Thomas JM, Sage T, Barry FA, Leduc M, Bon C et al. (2000). Collagen, convulxin, and thrombin stimulate aggregation-independent tyrosine phosphorylation of CD31 in platelets. Evidence for the involvement of Src family kinases. J Biol Chem 275: 27339-27347.
49. Cipollone F, Mezzetti A, Porreca E, Di Febbo C, Nutini M, Fazia M et al. (2002). Association between enhanced soluble CD40L and prothrombotic state in hypercholesterolemia: effects of statin therapy. Circulation 106: 399-402.
50. Clark EA, Shattil SJ, Ginsberg MH, Bolen J, Brugge JS (1994). Regulation of the protein tyrosine kinase pp72syk by platelet agonists and the integrin alpha IIb beta 3. J Biol Chem 269: 28859-28864.
51. Clemetson KJ, Clemetson JM, Proudfoot AEI, Power CA, Baggiolini M, Wells TN (2000). Functional expression of CCR1, CCR3, CCR4, and CXCR4 chemokine receptors on human platelets. Blood 96: 4046-4054.
52. Conrotto P, Valdembri D, Corso S, Serini G, Tamagnone L, Comoglio PM et al. (2005). Sema4D induces angiogenesis through met recruitment by Plexin B1. Blood 105: 4321-4329.
53. Damonneville M, Monte D, Auriault C, Capron A (1990). The neuropeptide substance P stimulates the effector functions of platelets. Clin Exp Immunol 81: 346-351.
54. Danese S, Scaldaferri F, Papa A, Pola R, Gasbarrini A, Sgambato A et al. (2004). CD40L-positive platelets induce CD40L expression de novo in endothelial cells: adding a loop to microvascular inflammation. Arterioscler Thromb Vasc Biol 24: e162.
55. Davi G, Patrono C (2007). Platelet activation and atherothrombosis. N Engl J Med 357: 2482-2494.
56. de Vet EC, Aguado B, Campbell RD (2001). G6b, a novel immunoglobulin superfamily member encoded in the human major histocompatibility complex, interacts with SHP-1 and SHP-2. J Biol Chem 276: 42070-42076.
57. de Vet EC, Newland SA, Lyons PA, Aguado B, Campbell RD (2005). The cell surface receptor G6b, a member of the immunoglobulin superfamily, binds heparin. FEBS Lett 579: 2355-2358.
58. Deaglio S, Morra M, Mallone R, Ausiello CM, Prager E, Garbarino G et al. (1998). Human CD38 (ADP-ribosyl cyclase) is a counter-receptor of CD31, an Ig superfamily member. J Immunol 160: 395-402.
59. Delaire S, Billard C, Tordjman R, Chedotal A, Elhabazi A, Bensussan A et al. (2001). Biological activity of soluble CD100. II. Soluble CD100, similarly to H-SemaIII, inhibits immune cell migration. J Immunol 166: 4348-4354.
60. DeLisser HM, Yan HC, Newman PJ, Muller WA, Buck CA, Albelda SM (1993). Platelet/endothelial cell adhesion molecule-1 (CD31)-mediated cellular aggregation involves cell surface glycosaminoglycans. J Biol Chem 268: 16037-16046.
61. Denis CV, Wagner DD (2007). Platelet adhesion receptors and their ligands in mouse models of thrombosis. Arterioscler Thromb Vasc Biol 27: 728-739.
62. Eitzman DT (2007). Regulation of hemostasis and thrombosis - insights from murine models. Arterioscler Thromb Vasc Biol 27: 453.
63. Elmi F, Peacock T, Schiavone J (2000). Isolated profound thrombocytopenia associated with clopidogrel. J Invasive Cardiol 12: 532-535.
64. Engel P, Eck MJ, Terhorst C (2003). The SAP and SLAM families in immune responses and X-linked lymphoproliferative disease. Nat Rev Immunol 3: 813-821.
65. Essex DW (2004). The role of thiols and disulfides in platelet function. Antioxid Redox Signal 6: 736-746.
66. Essex DW, Chen K, Swiatkowska M (1995). Localization of protein disulfide isomerase to the external surface of the platelet plasma membrane. Blood 86: 2168-2173.
67. Essex DW, Li M (1999). Protein disulphide isomerase mediates platelet aggregation and secretion. Br J Haematol 104: 448-454.
68. Essex DW, Li M (2006). Redox modification of platelet glycoproteins. Curr Drug Targets 7: 1233-1241.
69. Fabre JE, Nguyen M, Latour A, Keifer JA, Audoly LP, Coffman TM et al. (1999). Decreased platelet aggregation, increased bleeding time and resistance to thromboembolism in P2Y1-deficient mice. Nat Med 5: 1199-1202.
70. Falati S, Edmead CE, Poole AW (1999). Glycoprotein Ib-V-IX, a receptor for von Willebrand factor, couples physically and functionally to the Fc receptor gamma-chain, Fyn, and Lyn to activate human platelets. Blood 94: 1648-1656.
71. Falati S, Gross PL, Merrill-Skoloff G, Sim D, Flaumenhaft R, Celi A et al. (2004). In vivo models of platelet function and thrombosis: study of real-time thrombus formation. Meth Mol Biol 272: 187-197.
72. Falati S, Patil S, Gross PL, Stapleton M, Merrill-Skoloff G, Barrett NE et al. (2006). Platelet PECAM-1 inhibits thrombus formation in vivo. Blood 107: 535-541.
73. Fay WP, Parker AC, Ansari MN, Zheng X, Ginsburg D (1999). Vitronectin inhibits the thrombotic response to arterial injury in mice. Blood 93: 1825-1830.
74. Feijge MA, Ansink K, Vanschoonbeek K, Heemskerk JW (2004). Control of platelet activation by cyclic AMP turnover and cyclic nucleotide phosphodiesterase type-3. Biochem Pharmacol 67: 1559-1567.
75. Ferguson JJ (2006). The role of oral antiplatelet agents in atherothrombotic disease. Am J Cardiovasc Drugs 6: 149-157.
76. Ferrari DM, Soling HD (1999). The protein disulphide-isomerase family: unravelling a string of folds. Biochem J 339 (Part 1): 1-10.
77. Ferreira SH, Moncada S, Vane JR (1971). Indomethacin and aspirin abolish prostaglandin release from the spleen. Nat New Biol 231: 237-239.
78. Foster CJ, Prosser DM, Agans JM, Zhai Y, Smith MD, Lachowicz JE et al. (2001). Molecular identification and characterization of the platelet ADP receptor targeted by thienopyridine antithrombotic drugs. J Clin Invest 107: 1591-1598.
79. Foster FM, Traer CJ, Abraham SM, Fry MJ (2003). The phosphoinositide (PI) 3-kinase family. J Cell Sci 116: 3037-3040.
80. Furman MI, Krueger LA, Linden MD, Barnard MR, Frelinger AL, Michelson AD (2004). Release of soluble CD40L from platelets is regulated by glycoprotein IIb/IIIa and actin polymerization. J Am Coll Cardiol 43: 2319-2325.
81. Gachet C (2006). Regulation of platelet functions by P2 receptors. Annu Rev Pharmacol Toxicol 46: 277-300.
82. Gale NW, Holland SJ, Valenzuela DM, Flenniken A, Pan L, Ryan TE et al. (1996). Eph receptors and ligands comprise two major specificity subclasses and are reciprocally compartmentalized during embryogenesis. Neuron 17: 9-19.
83. Gattis JL, Washington AV, Chisholm MM, Quigley L, Szyk A, McVicar DW et al. (2006). The structure of the extracellular domain of triggering receptor expressed on myeloid cells like transcript-1 and evidence for a naturally occurring soluble fragment. J Biol Chem 281: 13396-13403.
84. Gear AR, Camerini D (2003). Platelet chemokines and chemokine receptors: linking hemostasis, inflammation, and host defense. Microcirculation 10: 335-350.
85. Gear ARL, Suttitanamongkol S, Viisoreanu D, Polanowska-Grabowska RK, Raha S, Camerini D (2001). Adenosine diphosphate strongly potentiates the ability of the chemokines MDC, TARC, and SDF-1 to stimulate platelet function. Blood 97: 937-945.
86. Genetta TB, Mauro VF (1996). ABCIXIMAB: a new antiaggregant used in angioplasty. Ann Pharmacother 30: 251-257.
87. Giancotti FG, Ruoslahti E (1999). Integrin signaling. Science 285: 1028-1032.
88. Gibbins J, Asselin J, Farndale R, Barnes M, Law CL, Watson SP (1996). Tyrosine phosphorylation of the Fc receptor gamma-chain in collagen-stimulated platelets. J Biol Chem 271: 18095-18099.
89. Gibbins JM (2004). Platelet adhesion signalling and the regulation of thrombus formation. J Cell Sci 117: 3415-3425.
90. Gibbins JM, Okuma M, Farndale R, Barnes M, Watson SP (1997). Glycoprotein VI is the collagen receptor in platelets which underlies tyrosine phosphorylation of the Fc receptor gamma-chain. FEBS Lett 413: 255-259.
91. Giomarelli B, Washington VA, Chisholm MM, Quigley L, McMahon JB, Mori T et al. (2007). Inhibition of thrombin-induced platelet aggregation using human single-chain Fv antibodies specific for TREM-like transcript-1. Thromb Haemost 97: 955-963.
92. Goncalves I, Hughan SC, Schoenwaelder SM, Yap CL, Yuan YP, Jackson SP (2003). Integrin alpha(IIb)beta(3)-dependent calcium signals regulate platelet-fibrinogen interactions under flow - involvement of phospholipase C gamma 2. J Biol Chem 278: 34812-34822.
93. Goshima Y, Ito T, Sasaki Y, Nakamura F (2002). Semaphorins as signals for cell repulsion and invasion. J Clin Invest 109: 993-998.
94. Gould WR, Baxi SM, Schroeder R, Peng YW, Leadley RJ, Peterson JT et al. (2005). Gas6 receptors Axl, Sky and Mer enhance platelet activation and regulate thrombotic responses. J Thromb Haemost 3: 733-741.
95. Graham GJ, Stevens JM, Page NM, Grant AD, Brain SD, Lowry PJ et al. (2004). Tachykinins regulate the function of platelets. Blood 104: 1058-1065.
96. Grewal IS, Flavell RA (1998). CD40 and CD154 in cell-mediated immunity. Annu Rev Immunol 16: 111-135.
97. Gudat F, Laubscher A, Otten U, Pletscher A (1981). Shape changes induced by biologically active peptides and nerve growth factor in blood platelets of rabbits. Br J Pharmacol 74: 533-538.
98. Gum PA, Kottke-Marchant K, Poggio ED, Gurm H, Welsh PA, Brooks L et al. (2001). Profile and prevalence of aspirin resistance in patients with cardiovascular disease. Am J Cardiol 88: 230-235.
99. Halushka PV (2000). Thromboxane A(2) receptors: where have you gone? Prostaglandins Other Lipid Mediat 60: 175-189.
100. Hamilton JR, Cornelissen I, Coughlin SR (2004). Impaired hemostasis and protection against thrombosis in protease-activated receptor 4-deficient mice is due to lack of thrombin signaling in platelets. J Thromb Haemost 2: 1429-1435.
101. Harrington RA, Armstrong PW, Graffagnino C, Van De Werf F, Kereiakes DJ, Sigmon KN et al. (2000). Dose-finding, safety, and tolerability study of an oral platelet glycoprotein IIb/IIIa inhibitor, lotrafiban, in patients with coronary or cerebral atherosclerotic disease. Circulation 102: 728-735.
102. He L, Pappan LK, Grenache DG, Li Z, Tollefsen DM, Santoro SA et al. (2003). The contributions of the alpha 2 beta 1 integrin to vascular thrombosis in vivo. Blood 102: 3652-3657.
103. Heemskerk JW, Siljander PR, Bevers EM, Farndale RW, Lindhout T (2000). Receptors and signalling mechanisms in the procoagulant response of platelets. Platelets 11: 301-306.
104. Henn V, Slupsky JR, Grafe M, Anagnostopoulos I, Forster R, Muller-Berghaus G et al. (1998). CD40 ligand on activated platelets triggers an inflammatory reaction of endothelial cells. Nature 391: 591-594.
105. Heptinstall S, Glenn JR, May JA, Storey RF, Wilcox RG (2004). Clopidogrel resistance. Catheter Cardiovasc Interv 63: 397-398.
106. Hirsch E, Bosco O, Tropel P, Laffargue M, Calvez R, Altruda F et al. (2001). Resistance to thromboembolism in PI3Kgamma-deficient mice. FASEB J 15: 2019-2021.
107. Hock B, Bohme B, Karn T, Yamamoto T, Kaibuchi K, Holtrich U et al. (1998). PDZ-domain-mediated interaction of the Eph-related receptor tyrosine kinase EphB3 and the ras-binding protein AF6 depends on the kinase activity of the receptor. Proc Natl Acad Sci USA 95: 9779-9784.
108. Hodivala-Dilke KM, McHugh KP, Tsakiris DA, Rayburn H, Crowley D, Ullman-Cullere M et al. (1999). Beta3-integrin-deficient mice are a model for Glanzmann thrombasthenia showing placental defects and reduced survival. J Clin Invest 103: 229-238.
109. Hollopeter G, Jantzen HM, Vincent D, Li G, England L, Ramakrishnan V et al. (2001). Identification of the platelet ADP receptor targeted by antithrombotic drugs. Nature 409: 202-207.
110. Holtkotter O, Nieswandt B, Smyth N, Muller W, Hafner M, Schulte V et al. (2002). Integrin alpha 2-deficient mice develop normally, are fertile, but display partially defective platelet interaction with collagen. J Biol Chem 277: 10789-10794.
111. Inoue T, Sohma R, Morooka S (1999). Cilostazol inhibits the expression of activation-dependent membrane surface glycoprotein on the surface of platelets stimulated in vitro. Thromb Res 93: 137-143.
112. Inwald DP, McDowall A, Peters MJ, Callard RE, Klein NJ (2003). CD40 is constitutively expressed on platelets and provides a novel mechanism for platelet activation. Circ Res 92: 1041-1048.
113. Irons BK, Greene RS, Mazzolini TA, Edwards KL, Sleeper RB (2006). Implications of rosiglitazone and pioglitazone on cardiovascular risk in patients with type 2 diabetes mellitus. Pharmacotherapy 26: 168-181.
114. Ischinger TA (1998). Antithrombotics in interventional cardiology: optimizing treatment and strategies. Am J Cardiol 82: 25L-28L.
115. Ishimoto Y, Nakano T (2000). Release of a product of growth arrest-specific gene 6 from rat platelets. FEBS Lett 466: 197-199.
116. Ito H, Miyakoda G, Mori T (2004). Cilostazol inhibits platelet-leukocyte interaction by suppression of platelet activation. Platelets 15: 293-301.
117. Jackson SP, Nesbitt WS, Kulkarni S (2003). Signaling events underlying thrombus formation. J Thromb Haemost 1: 1602-1612.
118. Jackson SP, Schoenwaelder SM (2003). Antiplatelet therapy: in search of the 'magic bullet'. Nat Rev Drug Discov 2: 775-789.
119. Jackson SP, Schoenwaelder SM, Goncalves I, Nesbitt WS, Yap CL, Wright CE et al. (2005). PI 3-kinase p110beta: a new target for antithrombotic therapy. Nat Med 11: 507-514.
120. Jackson SP, Schoenwaelder SM, Yuan Y, Rabinowitz I, Salem HH, Mitchell CA (1994). Adhesion receptor activation of phosphatidylinositol 3-kinase. von Willebrand factor stimulates the cytoskeletal association and activation of phosphatidylinositol 3-kinase and pp60c-src in human platelets. J Biol Chem 269: 27093-27099.
121. Jakubowski JA, Winters KJ, Naganuma H, Wallentin L (2007). Prasugrel: a novel thienopyridine antiplatelet agent. A review of preclinical and clinical studies and the mechanistic basis for its distinct antiplatelet profile. Cardiovasc Drug Rev 25: 357-374.
122. Jones KL, Hughan SC, Dopheide SM, Farndale RW, Jackson SP, Jackson DE (2001). Platelet endothelial cell adhesion molecule-1 is a negative regulator of platelet-collagen interactions. Blood 98: 1456-1463.
123. Jones S, Tucker KL, Sage T, Kaiser WJ, Barrett NE, Lowry PJ et al. (2007). Peripheral tachykinins and the neurokinin receptor NK1 are required for platelet thrombus formation. Blood 111: 605-612.
124. Jordan PA, Gibbins JM (2006). Extracellular disulfide exchange and the regulation of cellular function. Antioxid Redox Signal 8: 312-324.
125. Jordan PA, Stevens JM, Hubbard GP, Barrett NE, Sage T, Authi KS et al. (2005). A role for the thiol isomerase protein ERP5 in platelet function. Blood 105: 1500-1507.
126. Jung SM, Moroi M (1998). Platelets interact with soluble and insoluble collagens through characteristically different reactions. J Biol Chem 273: 14827-14837.
127. Jung SM, Moroi M (2000). Signal-transducing mechanisms involved in activation of the platelet collagen receptor integrin alpha(2)-beta(1). J Biol Chem 275: 8016-8026.
128. Kahn ML, Diacovo TG, Bainton DF, Lanza F, Trejo J, Coughlin SR (1999a). Glycoprotein V-deficient platelets have undiminished thrombin responsiveness and do not exhibit a Bernard-Soulier phenotype. Blood 94: 4112-4121.
129. Kahn ML, Nakanishi-Matsui M, Shapiro MJ, Ishihara H, Coughlin SR (1999b). Protease-activated receptors 1 and 4 mediate activation of human platelets by thrombin. J Clin Invest 103: 879-887.
130. Kahn ML, Zheng YW, Huang W, Bigornia V, Zeng D, Moff S et al. (1998). A dual thrombin receptor system for platelet activation. Nature 394: 690-694.
131. Kam PCA, Nethery CM (2003). The thienopyridine derivatives (platelet adenosine diphosphate receptor antagonists), pharmacology and clinical developments. Anaesthesia 58: 28-35.
132. Kameyoshi Y, Dorschner A, Mallet AI, Christophers E, Schroder JM (1992). Cytokine RANTES released by thrombin-stimulated platelets is a potent attractant for human eosinophils. J Exp Med 176: 587-592.
133. Kashiwagi H, Shiraga M, Kato H, Kamae T, Yamamoto N, Tadokoro S et al. (2005). Negative regulation of platelet function by a secreted cell repulsive protein, semaphorin 3A. Blood 106: 913-921.
134. Kasirer-Friede A, Cozzi MR, Mazzucato M, De Marco L, Ruggeri ZM, Shattil SJ (2004). Signaling through GP Ib-IX-V activates alpha IIb beta 3 independently of other receptors. Blood 103: 3403-3411.
135. Kato K, Kanaji T, Russell S, Kunicki TJ, Furihata K, Kanaji S et al. (2003). The contribution of glycoprotein VI to stable platelet adhesion and thrombus formation illustrated by targeted gene deletion. Blood 102: 1701-1707.
136. Kato K, Martinez C, Russell S, Nurden P, Nurden A, Fiering S et al. (2004). Genetic deletion of mouse platelet glycoprotein Ibbeta produces a Bernard-Soulier phenotype with increased alpha-granule size. Blood 104: 2339-2344.
137. Kauffenstein G, Bergmeier W, Eckly A, Ohlmann P, Leon C, Cazenave JP et al. (2001). The P2Y(12) receptor induces platelet aggregation through weak activation of the alpha(IIb)beta(3) integrin - a phosphoinositide 3-kinase-dependent mechanism. FEBS Lett 505: 281-290.
138. Kowalska MA, Ratajczak MZ, Majka M, Jin JG, Kunapuli S, Brass L et al. (2000). Stromal cell-derived factor-1 and macrophage-derived chemokine: 2 chemokines that activate platelets. Blood 96: 50-57.
139. Kurtz MM, Wang R, Clements MK, Cascieri MA, Austin CP, Cunningham BR et al. (2002). Identification, localization and receptor characterization of novel mammalian substance P-like peptides. Gene 296: 205-212.
140. Lago RM, Singh PP, Nesto RW (2007). Congestive heart failure and cardiovascular death in patients with prediabetes and type 2 diabetes given thiazolidinediones: a meta-analysis of randomised clinical trials. Lancet 370: 1129-1136.
141. Lahav J, Gofer-Dadosh N, Luboshitz J, Hess O, Shaklai M (2000). Protein disulfide isomerase mediates integrin-dependent adhesion. FEBS Lett 475: 89-92.
142. Lahav J, Jurk K, Hess O, Barnes MJ, Farndale RW, Luboshitz J et al. (2002). Sustained integrin ligation involves extracellular free sulfhydryls and enzymatically catalyzed disulfide exchange. Blood 100: 2472-2478.
143. Laman JD, De Boer M, Hart BA (1998). CD40 in clinical inflammation: from multiple sclerosis to atherosclerosis. Dev Immunol 6: 215-222.
144. Law DA, DeGuzman FR, Heiser P, Ministri-Madrid K, Killeen N, Phillips DR (1999). Integrin cytoplasmic tyrosine motif is required for outside-in alpha IIb beta 3 signalling and platelet function. Nature 401: 808-811.
145. Le Y, Zhou Y, Iribarren P, Wang J (2004). Chemokines and chemokine receptors: their manifold roles in homeostasis and disease. Cell Mol Immunol 1: 95-104.
146. Lederman S, Yellin MJ, Inghirami G, Lee JJ, Knowles DM, Chess L (1992). Molecular interactions mediating T-B lymphocyte collaboration in human lymphoid follicles. Roles of T cell-B-cell-activating molecule (5c8 antigen) and CD40 in contact-dependent help. J Immunol 149: 3817-3826.
147. Leger AJ, Covic L, Kuliopulos A (2006). Protease-activated receptors in cardiovascular diseases. Circulation 114: 1070-1077.
148. Leo A, Schraven B (2000). Networks in signal transduction: the role of adaptor proteins in platelet activation. Platelets 11: 429-445.
149. Leon C, Freund M, Ravanat C, Baurand A, Cazenave JP, Gachet C (2001). Key role of the P2Y(1) receptor in tissue factor-induced thrombin-dependent acute thromboembolism: studies in P2Y(1)-knockout mice and mice treated with a P2Y(1) antagonist. Circulation 103: 718-723.
150. Leon C, Hechler B, Freund M, Eckly A, Vial C, Ohlmann P et al. (1999). Defective platelet aggregation and increased resistance to thrombosis in purinergic P2Y(1) receptor-null mice. J Clin Invest 104: 1731-1737.
151. Lewis HD, Davis JW, Archibald DG, Steinke WE, Smitherman TC, Doherty JE et al. (1983). Protective effects of aspirin against acute myocardial-infarction and death in men with unstable angina - results of a 'Veterans-Administration-Cooperative Study'. N Engl J Med 309: 396-403.
152. Lian L, Wang Y, Draznin J, Eslin D, Bennett JS, Poncz M et al. (2005). The relative role of PLCbeta and PI3Kgamma in platelet activation. Blood 106: 110-117.
153. Lin D, Gish GD, Songyang Z, Pawson T (1999). The carboxyl terminus of B class ephrins constitutes a PDZ domain binding motif. J Biol Chem 274: 3726-3733.
154. Lipscombe LL, Gomes T, Levesque LE, Hux JE, Juurlink DN, Alter DA (2007). Thiazolidinediones and cardiovascular outcomes in older patients with diabetes. JAMA 298: 2634-2643.
155. Lopez JA, Andrews RK, Afshar-Kharghan V, Berndt MC (1998). Bernard-Soulier syndrome. Blood 91: 4397-4418.
156. Lutgens E, Cleutjens KB, Heeneman S, Koteliansky VE, Burkly LC, Daemen MJ (2000). Both early and delayed anti-CD40L antibody treatment induces a stable plaque phenotype. Proc Natl Acad Sci USA 97: 7464-7469.
157. Lutgens E, Gorelik L, Daemen MJ, de Muinck ED, Grewal IS, Koteliansky VE et al. (1999). Requirement for CD154 in the progression of atherosclerosis. Nat Med 5: 1313-1316.
158. Macaulay IC, Tijssen MR, Thijssen-Timmer DC, Gusnanto A, Steward M, Burns P et al. (2007). Comparative gene expression profiling of in vitro differentiated megakaryocytes and erythroblasts identifies novel activatory and inhibitory platelet membrane proteins. Blood 109: 3260-3269.
159. Mach F, Schonbeck U, Sukhova GK, Atkinson E, Libby P (1998). Reduction of atherosclerosis in mice by inhibition of CD40 signalling. Nature 394: 200-203.
160. Mahooti S, Graesser D, Patil S, Newman P, Duncan G, Mak T et al. (2000). PECAM-1 (CD31) expression modulates bleeding time in vivo. Am J Pathol 157: 75-81.
161. Mangin P, Nonne C, Eckly A, Ohlmann P, Freund M, Nieswandt B et al. (2003). A PLC gamma 2-independent platelet collagen aggregation requiring functional association of GPVI and integrin alpha(2)beta(1). FEBS Lett 542: 53-59.
162. Mangin P, Yap CL, Nonne C, Sturgeon SA, Goncalves I, Yuan Y et al. (2006). Thrombin overcomes the thrombosis defect associated with platelet GPVI/FcR gamma deficiency. Blood 107: 4346-4353.
163. Marx N, Imhof A, Froehlich J, Siam L, Ittner J, Wierse G et al. (2003). Effect of rosiglitazone treatment on soluble CD40L in patients with type 2 diabetes and coronary artery disease. Circulation 107: 1954-1957.
164. Mause SF, von Hundelshausen P, Zernecke A, Koenen RR, Weber C (2005). Platelet microparticles: a transcellular delivery system for RANTES promoting monocyte recruitment on endothelium. Arterioscler Thromb Vasc Biol 25: 1512-1518.
165. May AE, Kalsch T, Massberg S, Herouy Y, Schmidt R, Gawaz M (2002). Engagement of glycoprotein IIb/IIIa (alpha(IIb)beta(3)) on platelets upregulates CD40L and triggers CD40L-dependent matrix degradation by endothelial cells. Circulation 106: 2111-2117.
166. Mayr FB, Jilma B (2006). Current developments in anti-platelet therapy. Wien Med Wochenschr 156: 472-480.
167. Meadows TA, Bhatt DL (2007). Clinical aspects of platelet inhibitors and thrombus formation. Circ Res 100: 1261-1275.
168. Moog S, Mangin P, Lenain N, Strassel C, Ravanat C, Schuhler S et al. (2001). Platelet glycoprotein V binds to collagen and participates in platelet adhesion and aggregation. Blood 98: 1038-1046.
169. Moraes LA, Paul-Clark MJ, Rickman A, Flower RJ, Goulding NJ, Perretti M (2005). Ligand-specific glucocorticoid receptor activation in human platelets. Blood 106: 4167-4175.
170. Moraes LA, Swales KE, Wray JA, Damazo A, Gibbins JM, Warner TD et al. (2007). Nongenomic signaling of the retinoid X receptor through binding and inhibiting Gq in human platelets. Blood 109: 3741-3744.
171. Moroi M, Jung SM (2004). Platelet glycoprotein VI: its structure and function. Thromb Res 114: 221-233.
172. Moroi M, Jung SM, Okuma M, Shinmyozu K (1989). A patient with platelets deficient in glycoprotein VI that lack both collagen-induced aggregation and adhesion. J Clin Invest 84: 1440-1445.
173. Nagahama M, Nomura S, Kanazawa S, Ozaki Y, Kagawa H, Fukuhara S (2002). Significance of chemokines and soluble CD40 ligand in patients with autoimmune thrombocytopenic purpura. Eur J Haematol 69: 303-308.
174. Naik MU, Stalker TJ, Brass L, Nail UP (2007). Junctional adhesion molecule A (JAM-A) negatively regulates agonist-induced platelet activation. J Thromb Haemost 5 (Suppl 2): O-M-073.
175. Nanda N, Andre P, Bao M, Clauser K, Deguzman F, Howie D et al. (2005a). Platelet aggregation induces platelet aggregate stability via SLAM family receptor signaling. Blood 106: 3028-3034.
176. Nanda N, Bao M, Lin H, Clauser K, Komuves L, Quertermous T et al. (2005b). Platelet endothelial aggregation receptor 1 (PEAR1), a novel epidermal growth factor repeat-containing transmembrane receptor, participates in platelet contact-induced activation. J Biol Chem 280: 24680-24689.
177. Nanda N, Phillips DR (2006). Novel targets for antithrombotic drug discovery. Blood Cells Mol Dis 36: 228-231.
178. Nannizzi-Alaimo L, Alves VL, Phillips DR (2003). Inhibitory effects of
179. Nesbitt WS, Kulkarni S, Giuliano S, Goncalves I, Dopheide SM, Yap CL et al. (2002). Distinct glycoprotein Ib/V/IX and integrin alpha IIbbeta 3-dependent calcium signals cooperatively regulate platelet adhesion under flow. J Biol Chem 277: 2965-2972.
180. Newland SA, Macaulay IC, Floto AR, de Vet EC, Ouwehand WH, Watkins NA et al. (2007). The novel inhibitory receptor G6B is expressed on the surface of platelets and attenuates platelet function in vitro. Blood 109: 4806-4809.
181. Newman PJ, Berndt MJ, Gorski J, White GC, Lyman S, Paddock C et al. (1990). PECAM-1 (CD31) cloning and relation to adhesion molecules of the immunoglobulin gene superfamily. Science 247: 1219-1222.
182. Ni H, Freedman J (2003). Platelets in hemostasis and thrombosis: role of integrins and their ligands. Transfus Apher Sci 28: 257-264.
183. Ni H, Ramakrishnan V, Ruggeri ZM, Papalia JM, Phillips DR, Wagner DD (2001). Increased thrombogenesis and embolus formation in mice lacking glycoprotein V. Blood 98: 368-373.
184. Ni H, Yuen PS, Papalia JM, Trevithick JE, Sakai T, Fassler R et al. (2003). Plasma fibronectin promotes thrombus growth and stability in injured arterioles. Proc Natl Acad Sci USA 100: 2415-2419.
185. Nieswandt B, Aktas B, Moers A, Sachs UJH (2005). Platelets in atherothrombosis: lessons from mouse models. J Thromb Haemost 3: 1725-1736.
186. Nieswandt B, Brakebusch C, Bergmeier W, Schulte V, Bouvard D, Mokhtari-Nejad R et al. (2001a). Glycoprotein VI but not alpha2beta1 integrin is essential for platelet interaction with collagen. EMBO J 20: 2120-2130.
187. Nieswandt B, Schulte V, Bergmeier W, Mokhtari-Nejad R, Rackebrandt K, Cazenave JP et al. (2001b). Long-term antithrombotic protection by in vivo depletion of platelet glycoprotein VI in mice. J Exp Med 193: 459-469.
188. Nieswandt B, Watson SP (2003). Platelet-collagen interaction: is GPVI the central receptor? Blood 102: 449-461.
189. Nieuwenhuis HK, Akkerman JWN, Houdijk WPM, Sixma JJ (1985). Human-blood platelets showing no response to collagen fail to express surface glycoprotein-Ia. Nature 318: 470-472.
190. Niitsu Y, Jakubowski JA, Sugidachi A, Asai F (2005). Pharmacology of CS-747 (Prasugrel, LY640315), a novel, potent antiplatelet agent with in vivo P2Y(12) receptor antagonist activity. Semin Thromb Hemost 31: 184-194.
191. O'Neill S, Robinson A, Deering A, Ryan M, Fitzgerald DJ, Moran N (2000). The platelet integrin alpha IIbbeta 3 has an endogenous thiol isomerase activity. J Biol Chem 275: 36984-36990.
192. Obergfell A, Judd BA, del Pozo MA, Schwartz MA, Koretzky GA, Shattil SJ (2001). The molecular adapter SLP-76 relays signals from platelet integrin alphaIIbbeta3 to the actin cytoskeleton. J Biol Chem 276: 5916-5923.
193. Offermanns S, Hashimoto K, Watanabe M, Sun W, Kurihara H, Thompson RF et al. (1997a). Impaired motor coordination and persistent multiple climbing fiber innervation of cerebellar Purkinje cells in mice lacking G alpha q. Proc Natl Acad Sci USA 94: 14089-14094.
194. Offermanns S, Toombs CF, Hu YH, Simon MI (1997b). Defective platelet activation in G alpha(q)-deficient mice. Nature 389: 183-186.
195. Ohlen A, Thureson-Klein A, Lindbom L, Persson MG, Hedqvist P (1989). Substance P activates leukocytes and platelets in rabbit microvessels. Blood Vessels 26: 84-94.
196. Page NM, Bell NJ, Gardiner SM, Manyonda IT, Brayley KJ, Strange PG et al. (2003). Characterization of the endokinins: human tachykinins with cardiovascular activity. Proc Natl Acad Sci USA 100: 6245-6250.
197. Parry GC, Erlich JH, Carmeliet P, Luther T, Mackman N (1998). Low levels of tissue factor are compatible with development and hemostasis in mice. J Clin Invest 101: 560-569.
198. Patil S, Newman DK, Newman PJ (2001). Platelet endothelial cell adhesion molecule-1 serves as an inhibitory receptor that modulates platelet responses to collagen. Blood 97: 1727-1732.
199. Piali L, Hammel P, Uherek C, Bachmann F, Gisler RH, Dunon D et al. (1995). CD31/PECAM-1 is a ligand for alpha v beta 3 integrin involved in adhesion of leukocytes to endothelium. J Cell Biol 130: 451-460.
200. Podrez EA, Byzova TV, Febbraio M, Salomon RG, Ma Y, Valiyaveettil M et al. (2007). Platelet CD36 links hyperlipidemia, oxidant stress and a prothrombotic phenotype. Nat Med 13: 1086-1095.
201. Poole A, Gibbins JM, Turner M, van Vugt MJ, van de Winkel JG, Saito T et al. (1997). The Fc receptor gamma-chain and the tyrosine kinase Syk are essential for activation of mouse platelets by collagen. EMBO J 16: 2333-2341.
202. Popma JJ, Satler LF (1994). Early and late clinical outcome following coronary angioplasty performed with platelet glycoprotein IIb/IIIa receptor inhibition: the EPIC Trial results. J Invasive Cardiol 6 (Suppl A): 19A-28A; discussion 45A-50A.
203. Prevost N, Woulfe D, Tanaka T, Brass LF (2002). Interactions between Eph kinases and ephrins provide a mechanism to support platelet aggregation once cell-to-cell contact has occurred. Proc Natl Acad Sci USA 99: 9219-9224.
204. Prevost N, Woulfe DS, Jiang H, Stalker TJ, Marchese P, Ruggeri ZM et al. (2005). Eph kinases and ephrins support thrombus growth and stability by regulating integrin outside-in signaling in platelets. Proc Natl Acad Sci USA 102: 9820-9825.
205. Prevost N, Woulfe DS, Tognolini M, Tanaka T, Jian WY, Fortna RR et al. (2004). Signaling by ephrinB1 and EPh kinases in platelets promotes Rap1 activation, platelet adhesion, and aggregation via effector pathways that do not require phosphorylation of ephrinB1. Blood 103: 1348-1355.
206. Ramakrishnan V, Reeves PS, DeGuzman F, Deshpande U, Ministri-Madrid K, DuBridge RB et al. (1999). Increased thrombin responsiveness in platelets from mice lacking glycoprotein V. Proc Natl Acad Sci USA 96: 13336-13341.
207. RAPT Investigators (1994). Randomized trial of ridogrel, a combined thromboxane A2 synthase inhibitor and thromboxane A2/prostaglandin endoperoxide receptor antagonist, versus aspirin as adjunct to thrombolysis in patients with acute myocardial infarction. The Ridogrel versus Aspirin Patency Trial (RAPT). Circulation 89: 588-595.
208. Rathore V, Stapleton MA, Hillery CA, Montgomery RR, Nichols TC, Merricks EP et al. (2003). PECAM-1 negatively regulates GPIb/V/IX signaling in murine platelets. Blood 102: 3658-3664.
209. Reilly MP, Mohler III ER (2001). Cilostazol: treatment of intermittent claudication. Ann Pharmacother 35: 48-56.
210. Resendiz JC, Feng S, Ji G, Francis KA, Berndt MC, Kroll MH (2003). Purinergic P2Y12 receptor blockade inhibits shear-induced platelet phosphatidylinositol 3-kinase activation. Mol Pharmacol 63: 639-645.
211. Rottman JB (1999). Key role of chemokines and chemokine receptors in inflammation, immunity, neoplasia, and infectious disease. Vet Pathol 36: 357-367.
212. Roux S, Christeller S, Ludin E (1992). Effects of aspirin on coronary reocclusion and recurrent ischemia after thrombolysis - a meta-analysis. J Am Coll Cardiol 19: 671-677.
213. Ruggeri ZM (2007). The role of von Willebrand factor in thrombus formation. Thromb Res 120 (Suppl 1): S5-S9.
214. Ruiz C, Liu CY, Sun QH, Sigaud-Fiks M, Fressinaud E, Muller JY et al. (2001). A point mutation in the cysteine-rich domain of glycoprotein (GP) IIIa results in the expression of a GPIIb-IIIa (alphaIIbbeta3) integrin receptor locked in a high-affinity state and a Glanzmann thrombasthenia-like phenotype. Blood 98: 2432-2441.
215. Sachs UJ, Andrei-Selmer CL, Maniar A, Weiss T, Paddock C, Orlova VV et al. (2007). The neutrophil specific antigen CD177 is a counter-receptor for endothelial PECAM-1 (CD31). J Biol Chem 282: 23603-23612.
216. Saelman EUM, Kehrel B, Hese KM, Degroot PG, Sixma JJ, Nieuwenhuis HK (1994). Platelet-adhesion to collagen and endothelial-cell matrix under flow conditions is not dependent on platelet glycoprotein-Iv. Blood 83: 3240-3244.
217. Sakai T, Johnson KJ, Murozono M, Sakai K, Magnuson MA, Wieloch T et al. (2001). Plasma fibronectin supports neuronal survival and reduces brain injury following transient focal cerebral ischemia but is not essential for skin-wound healing and hemostasis. Nat Med 7: 324-330.
218. Savage B, Saldivar E, Ruggeri ZM (1996). Initiation of platelet adhesion by arrest onto fibrinogen or translocation on von Willebrand factor. Cell 84: 289-297.
219. Savi P, Laplace MC, Le Fur G, Emonds-Alt X, Herbert JM (1992). The NK1 receptor is involved in the neurokinin-induced shape change of rabbit platelets. FEBS Lett 312: 200-202.
220. Scarborough RM, Kleiman NS, Phillips DR (1999). Platelet glycoprotein IIb/IIIa antagonists. What are the relevant issues concerning their pharmacology and clinical use? Circulation 100: 437-444.
221. Schmugge M, Rand ML, Freedman J (2003). Platelets and von Willebrand factor. Transfus Apher Sci 28: 269-277.
222. Senis YA, Tomlinson MG, Garcia A, Dumon S, Heath VL, Herbert J et al. (2007). A comprehensive proteomics and genomics analysis reveals novel transmembrane proteins in human platelets and mouse megakaryocytes including G6b-B, a novel immunoreceptor tyrosine-based inhibitory motif protein. Mol Cell Proteomics 6: 548-564.
223. Serini G, Valdembri D, Zanivan S, Morterra G, Burkhardt C, Caccavari F et al. (2003). Class 3 semaphorins control vascular morphogenesis by inhibiting integrin function. Nature 424: 391-397.
224. Sevier CS, Kaiser CA (2002). Formation and transfer of disulphide bonds in living cells. Nat Rev Mol Cell Biol 3: 836-847.
225. Shattil SJ (1999). Signaling through platelet integrin alpha IIb beta 3: inside-out, outside-in, and sideways. Thromb Haemost 82: 318-325.
226. Shattil SJ, Kashiwagi H, Pampori N (1998). Integrin signaling: the platelet paradigm. Blood 91: 2645-2657.
227. Shattil SJ, Newman PJ (2004). Integrins: dynamic scaffolds for adhesion and signaling in platelets. Blood 104: 1606-1615.
228. Shenkman B, Brill A, Brill G, Lider O, Savion N, Varon D (2004). Differential response of platelets to chemokines: RANTES non-competitively inhibits stimulatory effect of SDF-1 alpha. J Thromb Haemost 2: 154-160.
229. Siess W, Siegel FL, Lapetina EG (1983). Arachidonic acid stimulates the formation of 1,2-diacylglycerol and phosphatidic acid in human platelets. Degree of phospholipase C activation correlates with protein phosphorylation, platelet shape change, serotonin release, and aggregation. J Biol Chem 258: 11236-11242.
230. Sim DS, Merrill-Skoloff G, Furie BC, Furie B, Flaumenhaft R (2004). Initial accumulation of platelets during arterial thrombus formation in vivo is inhibited by elevation of basal cAMP levels. Blood 103: 2127-2134.
231. Smith JB, Willis AL (1971). Aspirin selectively inhibits prostaglandin production in human platelets. Nat New Biol 231: 235-237.
232. Smyth SS, Reis ED, Vaananen H, Zhang W, Coller BS (2001). Variable protection of beta 3-integrin-deficient mice from thrombosis initiated by different mechanisms. Blood 98: 1055-1062.
233. Stalker TJ, Wu J, Hall RA, Brass LF (2007). The tight junction protein ESAM is recruited to platelet-platelet contacts and forms signaling complexes that affect thrombus growth and stability. J Thromb Haemost 5 (Suppl 2): O-M-073.
234. Steinhubl SR, Moliterno DJ (2005). The role of the platelet in the pathogenesis of atherothrombosis. Am J Cardiovasc Drugs 5: 399-408.
235. Suttitanamongkol S, Gear ARL (2001). ADP receptor antagonists inhibit platelet aggregation induced by the chemokines SDF-1, MDC and TARC. FEBS Lett 490: 84-87.
236. Tadokoro S, Shattil SJ, Eto K, Tai V, Liddington RC, de Pereda JM et al. (2003). Talin binding to integrin beta tails: a final common step in integrin activation. Science 302: 103-106.
237. Takahashi R, Sekine N, Nakatake T (1999). Influence of monoclonal antiplatelet glycoprotein antibodies on in vitro human megakaryocyte colony formation and proplatelet formation. Blood 93: 1951-1958.
238. Tamagnone L, Comoglio PM (2000). Signalling by semaphorin receptors: cell guidance and beyond. Trends Cell Biol 10: 377-383.
239. Tandon NN, Kralisz U, Jamieson GA (1989). Identification of glycoprotein IV (CD36) as a primary receptor for platelet-collagen adhesion. J Biol Chem 264: 7576-7583.
240. Thebault JJ, Kieffer G, Cariou R (1999). Single-dose pharmacodynamics of clopidogrel. Semin Thromb Hemost 25 (Suppl 2): 3-8.
241. Theroux P, Ouimet H, McCans J, Latour JG, Joly P, Levy G et al. (1988). Aspirin, heparin, or both to treat acute unstable angina. N Engl J Med 319: 1105-1111.
242. Thomas DW, Mannon RB, Mannon PJ, Latour A, Oliver JA, Hoffman M et al. (1998). Coagulation defects and altered hemodynamic responses in mice lacking receptors for thromboxane A2. J Clin Invest 102: 1994-2001.
243. Tolhurst G, Vial C, Leon C, Gachet C, Evans RJ, Mahaut-Smith MP (2005). Interplay between P2Y(1), P2Y(12), and P2X(1) receptors in the activation of megakaryocyte cation influx currents by ADP: evidence that the primary megakaryocyte represents a fully functional model of platelet P2 receptor signaling. Blood 106: 1644-1651.
244. Topol EJ, Lincoff AM, Kereiakes DJ, Kleiman NS, Cohen EA, Ferguson JJ et al. (2002). Multi-year follow-up of abciximab therapy in three randomized, placebo-controlled trials of percutaneous coronary revascularization. Am J Med 113: 1-6.
245. Tronik-Le Roux D, Roullot V, Poujol C, Kortulewski T, Nurden P, Marguerie G (2000). Thrombasthenic mice generated by replacement of the integrin alpha(IIb) gene: demonstration that transcriptional activation of this megakaryocytic locus precedes lineage commitment. Blood 96: 1399-1408.
246. Tsuji M, Ezumi Y, Arai M, Takayama H (1997). A novel association of Fc receptor gamma-chain with glycoprotein VI and their coexpression as a collagen receptor in human platelets. J Biol Chem 272: 23528-23531.
247. Valiyaveettil M, Kar N, Ashraf MZ, Byzova TV, Febbraio M, Podrez EA (2008). Oxidized high-density lipoprotein inhibits platelet activation and aggregation via scavenger receptor BI. Blood 111: 1962-1971.
248. van Kooten C, Banchereau J (2000). CD40-CD40 ligand. J Leukoc Biol 67: 2-17.
249. Vane JR (1971). Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nat New Biol 231: 232-235.
250. Vane JR, Botting RM (2003). The mechanism of action of aspirin. Thromb Res 110: 255-258.
251. Vanhaesebroeck B, Leevers SJ, Panayotou G, Waterfield MD (1997). Phosphoinositide 3-kinases: a conserved family of signal transducers. Trends Biochem Sci 22: 267-272.
252. Vollmar B, Schmits R, Kunz D, Menger MD (2001). Lack of in vivo function of CD31 in vascular thrombosis. Thromb Haemost 85: 160-164.
253. von Hundelshausen P, Weber C (2007). Platelets as immune cells: bridging inflammation and cardiovascular disease. Circ Res 100: 27-40.
254. Wallentin L (1990). Risk of myocardial-infarction and death during treatment with low-dose aspirin and intravenous heparin in men with unstable coronary-artery disease. Lancet 336: 827-830.
255. Walsh GM, Sheehan D, Kinsella A, Moran N, O'Neill S (2004). Redox modulation of integrin (correction of integin) alpha IIb beta 3 involves a novel allosteric regulation of its thiol isomerase activity. Biochemistry 43: 473-480.
256. Ware J, Russell S, Ruggeri ZM (2000). Generation and rescue of a murine model of platelet dysfunction: the Bernard-Soulier syndrome. Proc Natl Acad Sci USA 97: 2803-2808.
257. Washington AV, Quigley L, McVicar DW (2002). Initial characterization of TREM-like transcript (TLT)-1: a putative inhibitory receptor within the TREM cluster. Blood 100: 3822-3824.
258. Washington AV, Schubert RL, Quigley L, Disipio T, Feltz R, Cho EH et al. (2004). A TREM family member, TLT-1, is found exclusively in the alpha-granules of megakaryocytes and platelets. Blood 104: 1042-1047.
259. Watanabe N, Nakajima H, Suzuki H, Oda A, Matsubara Y, Moroi M et al. (2003). Functional phenotype of phosphoinositide 3-kinase p85alpha-null platelets characterized by an impaired response to GP VI stimulation. Blood 102: 541-548.
260. Watson SP, Auger JM, McCarty OJ, Pearce AC (2005). GPVI and integrin alphaIIb beta3 signaling in platelets. J Thromb Haemost 3: 1752-1762.
261. Weiss EJ, Hamilton JR, Lease KE, Coughlin SR (2002). Protection against thrombosis in mice lacking PAR3. Blood 100: 3240-3244.
262. Westrick RJ, Winn ME, Eitzman DT (2007). Murine models of vascular thrombosis (Eitzman series). Arterioscler Thromb Vasc Biol 27: 2079-2093.
263. Woulfe D, Jiang H, Morgans A, Monks R, Birnbaum M, Brass LF (2004). Defects in secretion, aggregation, and thrombus formation in platelets from mice lacking Akt2. J Clin Invest 113: 441-450.
264. Wu CC, Teng CM (2006). Comparison of the effects of PAR1 antagonists, PAR4 antagonists, and their combinations on thrombin-induced human platelet activation. Eur J Pharmacol 546: 142-147.
265. Wu DM, Meiring M, Kotze HF, Deckmyn H, Cauwenberghs N (2002). Inhibition of platelet glycoprotein Ib, glycoprotein IIb/IIIa, or both by monoclonal antibodies prevents arterial thrombosis in baboons. Arterioscler Thromb Vasc Biol 22: 323-328.
266. Yamamoto N, Akamatsu N, Yamazaki H, Tanoue K (1992). Normal aggregations of glycoprotein-Iv (Cd36)-deficient platelets from 7 healthy Japanese donors. Br J Haematol 81: 86-92.
267. Yan B, Smith JW (2000). A redox site involved in integrin activation. J Biol Chem 275: 39964-39972.
268. Yan B, Smith JW (2001). Mechanism of integrin activation by disulfide bond reduction. Biochemistry 40: 8861-8867.
269. Zhang J, Vanhaesebroeck B, Rittenhouse SE (2002). Human platelets contain p110delta phosphoinositide 3-kinase. Biochem Biophys Res Commun 296: 178-181.
270. Zhang Y, Lu LW, Furlonger C, Wu GE, Paige CJ (2000). Hemokinin is a hematopoietic-specific tachykinin that regulates B lymphocytes. Nat Immunol 1: 392-397.
271. Zhu L, Bergmeier W, Wu J, Jiang H, Stalker TJ, Cieslak M et al. (2007). Regulated surface expression and shedding support a dual role for semaphorin 4D in platelet responses to vascular injury. Proc Natl Acad Sci USA 104: 1621-1626.
272. Zumbach A, Marbet GA, Tsakiris DA (2001). Influence of the genetic background on platelet function, microparticle and thrombin generation in the common laboratory mouse. Platelets 12: 496-502.