Platelet physiology and antiplatelet agents

Clinical Chemistry and Laboratory Medicine

Volumn 48, Issue SUPPL. 1, 2010, Pages

  Thijs, Tim ^a   Nuyttens, Benedicte P ^a   Deckmyn, Hans ^a   Broos, Katleen ^a  

^a UNIVERSITY OF LEUVEN   (Belgium)

Author keywords

antiplatelet agents; platelet activation; platelet adhesion; platelet aggregation; platelet inhibition

Indexed keywords

3A,4,4A,5,6,7,8,8A,9,9A DECAHYDRO N [4 [2 [5 (3 FLUOROPHENYL) 2 PYRIDYL]VINYL] 3 METHYL 1 OXO 3H BENZO[F]ISOBENZOFURAN 7 YL]CARBAMIC ACID ETHYL ESTER; ACETYLSALICYLIC ACID; ANTITHROMBOCYTIC AGENT; CLOPIDOGREL; COLLAGEN RECEPTOR; G PROTEIN COUPLED RECEPTOR; GLYCOPROTEIN IB; NITRIC OXIDE; PHOSPHOLIPASE A2; PHOSPHOLIPASE C; THROMBOXANE A2;

CALCIUM TRANSPORT; CORONARY ARTERY DISEASE; HUMAN; INTRACELLULAR SIGNALING; NONHUMAN; PRIORITY JOURNAL; REVIEW; SIGNAL TRANSDUCTION; THROMBOCYTE; THROMBOCYTE ACTIVATION; THROMBOCYTE ADHESION; THROMBOCYTE AGGREGATION;

BLOOD PLATELETS; BLOOD PROTEINS; CELL ADHESION; HUMANS; PLATELET ACTIVATION; PLATELET AGGREGATION INHIBITORS;

EID: 79251648429     PISSN: 14346621     EISSN: 14374331     Source Type: Journal    
DOI: 10.1515/CCLM.2010.363     Document Type: Review

References (119)

1. Jones CI, Bray S, Garner SF, Stephens J, de Bono B, Angenent WG, et al. A functional genomics approach reveals novel quantitative trait loci associated with platelet signaling pathways. Blood 2009;114:1405-16.
2. Macaulay IC, Carr P, Gusnanto A, Ouwehand WH, Fitzgerald D, Watkins NA. Platelet genomics and proteomics in human health and disease. J Clin Invest 2005;115:3370-7.
3. Watkins NA, Gusnanto A, de Bono B, De S, Miranda-Saavedra D, Hardie DL, et al. A HaemAtlas: Characterizing gene expression in differentiated human blood cells. Blood 2009;113:e1-9.
4. Ouwehand WH. Platelet genomics and the risk of atherothrombosis. J Thromb Haemost 2007;5(Suppl 1):188-95.
5. Macaulay IC, Tijssen MR, Thijssen-Timmer DC, Gusnanto A, Steward M, Burns P, et al. Comparative gene expression profiling of in vitro differentiated megakaryocytes and erythroblasts identifies novel activatory and inhibitory platelet membrane proteins. Blood 2007;109:3260-9.
6. Qureshi AH, Chaoji V, Maiguel D, Faridi MH, Barth CJ, Salem SM, et al. Proteomic and phospho-proteomic profile of human platelets in basal, resting state: Insights into integrin signaling. PLoS One 2009;4:e7627.
7. O'Connor MN, Salles II, Cvejic A, Watkins NA, Walker A, Garner SF, et al. Functional genomics in zebrafish permits rapid characterization of novel platelet membrane proteins. Blood 2009;113:4754-62.
8. Lang MR, Gihr G, Gawaz MP, Muller II. Haemostasis in Danio rerio: Is the zebrafish a useful model for platelet research? J Thromb Haemost 2010;8:1159-69. Epub 2010 Feb 17.
9. Salles II, Thijs T, Brunaud C, De Meyer SF, Thys J, Vanhoorelbeke K, et al. Human platelets produced in NOD/SCID mice upon transplantation of human cord blood CD34q cells are functionally active in an ex vivo flow model of thrombosis. Blood 2009;114:5044-51.
10. Deckmyn H, Vanhoorelbeke K, Ulrichts H, Schoolmeesters A, Staelens S, De Meyer S. Amplification loops and signal transduction pathways in platelets. In: Arnout J, de Gaetano G, Hoylaerts MF, Peerlinck K, Van Geet C, Verhaeghe R, editors. Thrombosis Fundamental and Clinical Aspects. Leuven: Leuven University Press, 2003:75-91.
11. Savage B, Almus-Jacobs F, Ruggeri ZM. Specific synergy of multiple substrate-receptor interactions in platelet thrombus formation under flow. Cell 1998;94:657-66.
12. Salles II, Feys HB, Iserbyt BF, De Meyer SF, Vanhoorelbeke K, Deckmyn H. Inherited traits affecting platelet function. Blood Rev 2008;22:155-72.
13. De Meyer SF, Deckmyn H, Vanhoorelbeke K. von Willebrand factor to the rescue. Blood 2009;113:5049-57.
14. Luo SZ, Mo X, Afshar-Kharghan V, Srinivasan S, Lopez JA, Li R. Glycoprotein Ibalpha forms disulfide bonds with 2 glycoprotein Ibbeta subunits in the resting platelet. Blood 2007; 109:603-9.
15. Dumas JJ, Kumar R, McDonagh T, Sullivan F, Stahl ML, Somers WS, et al. Crystal structure of the wild-type von Willebrand factor A1-glycoprotein Ibalpha complex reveals conformation differences with a complex bearing von Willebrand disease mutations. J Biol Chem 2004;279:23327-34.
16. Huizinga EG, Tsuji S, Romijn RA, Schiphorst ME, de Groot PG, Sixma JJ, et al. Structures of glycoprotein Ibalpha and its complex with von Willebrand factor A1 domain. Science 2002;297:1176-9.
17. Wu Y, Suzuki-Inoue K, Satoh K, Asazuma N, Yatomi Y, Berndt MC, et al. Role of Fc receptor gamma-chain in platelet glycoprotein Ib-mediated signaling. Blood 2001;97:3836-45.
18. Mangin PH, Receveur N, Wurtz V, David T, Gachet C, Lanza F. Identification of five novel 14-3-3 isoforms interacting with the GPIb-IX complex in platelets. J Thromb Haemost 2009; 7:1550-5.
19. Jain S, Zuka M, Liu J, Russell S, Dent J, Guerrero JA, et al. Platelet glycoprotein Ib alpha supports experimental lung metastasis. Proc Natl Acad Sci USA 2007;104:9024-8.
20. Yuan Y, Zhang W, Yan R, Liao Y, Zhao L, Ruan C, et al. Identification of a novel 14-3-3zeta binding site within the cytoplasmic domain of platelet glycoprotein Ibalpha that plays a key role in regulating the von Willebrand factor binding function of glycoprotein Ib-IX. Circ Res 2009;105:1177-85.
21. Mu FT, Cranmer SL, Andrews RK, Berndt MC. Functional association of phosphoinositide-3-kinase with platelet glycoprotein Ibalpha, the major ligand-binding subunit of the glycoprotein Ib-IX-V complex. J Thromb Haemost 2010;8: 324-30.
22. Andrews RK, Munday AD, Mitchell CA, Berndt MC. Interaction of calmodulin with the cytoplasmic domain of the platelet membrane glycoprotein Ib-IX-V complex. Blood 2001;98:681-7.
23. Wu Y, Asazuma N, Satoh K, Yatomi Y, Takafuta T, Berndt MC, et al. Interaction between von Willebrand factor and glycoprotein Ib activates Src kinase in human platelets: Role of phosphoinositide 3-kinase. Blood 2003;101:3469-76.
24. Kasirer-Friede A, Moran B, Nagrampa-Orje J, Swanson K, Ruggeri ZM, Schraven B, et al. ADAP is required for normal alphaIIbbeta3 activation by VWF/GP Ib-IX-V and other agonists. Blood 2007;109:1018-25.
25. Schade AJ, Arya M, Gao S, Diz-Kucukkaya R, Anvari B, McIntire LV, et al. Cytoplasmic truncation of glycoprotein Ib alpha weakens its interaction with von Willebrand factor and impairs cell adhesion. Biochemistry 2003;42:2245-51.
26. Gilbert JC, Feo-Fraulini T, Hutabarat RM, Horvath CJ, Merlino PG, Marsh HN, et al. First-in-human evaluation of anti von Willebrand factor therapeutic aptamer ARC1779 in healthy volunteers. Circulation 2007;116:2678-86.
27. Mayr FB, Knobl P, Jilma B, Siller-Matula JM, Wagner PG, Schaub RG, et al. The aptamer ARC1779 blocks von Willebrand factor-dependent platelet function in patients with thrombotic thrombocytopenic purpura ex vivo. Transfusion 2010;50:1079-85.
28. Bartunek J, Barbato E, Holz JB, Vercruysse K, Ulrichts H, Heyndrickx G. ALX-0081 a novel anti-thrombotic: Results of a single-dose phase 1 study in healthy volunteers and further development in patients with stable angina undergoing PCI. Circulation 2008;118:S656.
29. Vanhoorelbeke K, Ulrichts H, Van De Walle G, Fontayne A, Deckmyn H. Inhibition of platelet glycoprotein Ib and its antithrombotic potential. Curr Pharm Des 2007;13:2684-97.
30. Cauwenberghs N, Meiring M, Vauterin S, van Wyk V, Lamprecht S, Roodt JP, et al. Antithrombotic effect of platelet glycoprotein Ib-blocking monoclonal antibody Fab fragments in nonhuman primates. Arterioscler Thromb Vasc Biol 2000; 20:1347-53.
31. Nieswandt B, Bergmeier W, Schulte V, Rackebrandt K, Gessner JE, Zirngibl H. Expression and function of the mouse collagen receptor glycoprotein VI is strictly dependent on its association with the FcRgamma chain. J Biol Chem 2000; 275:23998-4002.
32. Ezumi Y, Shindoh K, Tsuji M, Takayama H. Physical and functional association of the Src family kinases Fyn and Lyn with the collagen receptor glycoprotein VI-Fc receptor gamma chain complex on human platelets. J Exp Med 1998;188: 267-76.
33. Ichinohe T, Takayama H, Ezumi Y, Arai M, Yamamoto N, Takahashi H, et al. Collagen-stimulated activation of Syk but not c-Src is severely compromised in human platelets lacking membrane glycoprotein VI. J Biol Chem 1997;272:63-8.
34. Pasquet JM, Gross B, Quek L, Asazuma N, Zhang W, Sommers CL, et al. LAT is required for tyrosine phosphorylation of phospholipase cgamma2 and platelet activation by the collagen receptor GPVI. Mol Cell Biol 1999;19:8326-34.
35. Santoro SA. Identification of a 160,000 dalton platelet membrane protein that mediates the initial divalent cationdependent adhesion of platelets to collagen. Cell 1986;46: 913-20.
36. Staatz WD, Rajpara SM, Wayner EA, Carter WG, Santoro SA. The membrane glycoprotein Ia-IIa (VLA-2) complex mediates the Mgqq-dependent adhesion of platelets to collagen. J Cell Biol 1989;108:1917-24.
37. Van de Walle GR, Schoolmeester A, Iserbyt BF, Cosemans JM, Heemskerk JW, Hoylaerts MF, et al. Activation of alphaIIbbeta3 is a sufficient but also an imperative prerequisite for activation of alpha2beta1 on platelets. Blood 2007; 109:595-602.
38. Emsley J, Knight CG, Farndale RW, Barnes MJ, Liddington RC. Structural basis of collagen recognition by integrin alpha2beta1. Cell 2000;101:47-56.
39. Knight CG, Morton LF, Onley DJ, Peachey AR, Messent AJ, Smethurst PA, et al. Identification in collagen type I of an integrin alpha2 beta1-binding site containing an essential GER sequence. J Biol Chem 1998;273:33287-94.
40. Raynal N, Hamaia SW, Siljander PR, Maddox B, Peachey AR, Fernandez R, et al. Use of synthetic peptides to locate novel integrin alpha2beta1-binding motifs in human collagen III. J Biol Chem 2006;281:3821-31.
41. Verkleij MW, Ijsseldijk MJ, Heijnen-Snyder GJ, Huizinga EG, Morton LF, Knight CG, et al. Adhesive domains in the collagen III fragment alpha1(III)CB4 that support alpha2beta1- and von Willebrand factor-mediated platelet adhesion under flow conditions. Thromb Haemost 1999;82: 1137-44.
42. Xu Y, Gurusiddappa S, Rich RL, Owens RT, Keene DR, Mayne R, et al. Multiple binding sites in collagen type I for the integrins alpha1beta1 and alpha2beta1. J Biol Chem 2000;275:38981-9.
43. Iserbyt BF. Insights in platelet integrin alpha2beta1 affinity modulation. wdissertationx. Kortrijk: KU Leuven campus Kortrijk; 2010.
44. Inoue O, Suzuki-Inoue K, Dean WL, Frampton J, Watson SP. Integrin alpha2beta1 mediates outside-in regulation of platelet spreading on collagen through activation of Src kinases and PLCgamma2. J Cell Biol 2003;160:769-80.
45. Auger JM, Kuijpers MJ, Senis YA, Watson SP, Heemskerk JW. Adhesion of human and mouse platelets to collagen under shear: A unifying model. FASEB J 2005;19:825-7.
46. Pugh N, Simpson AM, Smethurst PA, de Groot PG, Raynal N, Farndale RW. Synergism between platelet collagen receptors defined using receptor-specific collagen-mimetic peptide substrata in flowing blood. Blood 2010;115:5069-79.
47. De Meyer SF, Vanhoorelbeke K, Broos K, Salles II, Deckmyn H. Antiplatelet drugs. Br J Haematol 2008;142:515-28.
48. Matsumoto Y, Takizawa H, Nakama K, Gong X, Yamada Y, Tandon NN, et al. Ex vivo evaluation of anti-GPVI antibody in cynomolgus monkeys: Dissociation between anti-platelet aggregatory effect and bleeding time. Thromb Haemost 2006; 96:167-75.
49. Ohlmann P, Hechler B, Ravanat C, Loyau S, Herrenschmidt N, Wanert F, et al. Ex vivo inhibition of thrombus formation by an anti-glycoprotein VI Fab fragment in non-human primates without modification of glycoprotein VI expression. J Thromb Haemost 2008;6:1003-11.
50. Grothusen C, Umbreen S, Konrad I, Stellos K, Schulz C, Schmidt B, et al. EXP3179 inhibits collagen-dependent platelet activation via glycoprotein receptor-VI independent of AT1-receptor antagonism: Potential impact on atherothrombosis. Arterioscler Thromb Vasc Biol 2007;27:1184-90.
51. Ono K, Ueda H, Yoshizawa Y, Akazawa D, Tanimura R, Shimada I, et al. Structural basis for platelet antiaggregation by angiotensin II type 1 receptor antagonist losartan (DuP-753) via glycoprotein VI. J Med Chem 2010;53:2087-93.
52. Grosse J, Braun A, Varga-Szabo D, Beyersdorf N, Schneider B, Zeitlmann L, et al. An EF hand mutation in Stim1 causes premature platelet activation and bleeding in mice. J Clin Invest 2007;117:3540-50.
53. Bergmeier W, Oh-Hora M, McCarl CA, Roden RC, Bray PF, Feske S. R93W mutation in Orai1 causes impaired calcium influx in platelets. Blood 2009;113:675-8.
54. Muller F, Mutch NJ, Schenk WA, Smith SA, Esterl L, Spronk HM, et al. Platelet polyphosphates are proinflammatory and procoagulant mediators in vivo. Cell 2009;139:1143-56.
55. Habib A, Vezza R, Creminon C, Maclouf J, FitzGerald GA. Rapid, agonist-dependent phosphorylation in vivo of human thromboxane receptor isoforms. Minimal involvement of protein kinase C. J Biol Chem 1997;272:7191-200.
56. Elzagallaai A, Rose SD, Trifaro JM. Platelet secretion induced by phorbol esters stimulation is mediated through phosphorylation of MARCKS: A MARCKS-derived peptide blocks MARCKS phosphorylation and serotonin release without affecting pleckstrin phosphorylation. Blood 2000;95:894-902.
57. Hoylaerts MF. Amplification loops: Release reaction. In: Gresele P, Page CV, Fuster V, Vermeylen J, editors. Platelets in thrombotic and non-thrombotic disorders. Cambridge, UK: Cambridge University Press, 2002:357-68.
58. Stefanini L, Roden RC, Bergmeier W. CalDAG-GEFI is at the nexus of calcium-dependent platelet activation. Blood 2009; 114:2506-14.
59. Lin LL, Wartmann M, Lin AY, Knopf JL, Seth A, Davis RJ. cPLA2 is phosphorylated and activated by MAP kinase. Cell 1993;72:269-78.
60. Moers A, Wettschureck N, Gruner S, Nieswandt B, Offermanns S. Unresponsiveness of platelets lacking both Galpha( q) and Galpha(13). Implications for collagen-induced platelet activation. J Biol Chem 2004;279:45354-9.
61. Offermanns S, Laugwitz KL, Spicher K, Schultz G. G-Proteins of the G(12) family are activated via thromboxane A(2) and thrombin receptors in human platelets. Proc Natl Acad Sci USA 1994;91:504-8.
62. Loll PJ, Picot D, Garavito RM. The structural basis of aspirin activity inferred from the crystal structure of inactivated prostaglandin H2 synthase. Nat Struct Biol 1995;2:637-43.
63. Lièvre M, Cucherat M. Aspirin in the secondary prevention of cardiovascular disease: An update of the APTC meta-analysis. Fundam Clin Pharmacol 2009;24:385-91.
64. Hu H, Hoylaerts MF. The P2X1 ion channel in platelet function. Platelets 2010;21:153-66.
65. Gould WR, Baxi SM, Schroeder R, Peng YW, Leadley RJ, Peterson JT, et al. Gas6 receptors Axl, Sky and Mer enhance platelet activation and regulate thrombotic responses. J Thromb Haemost 2005;3:733-41.
66. Brass LF, Manning DR, Cichowski K, Abrams CS. Signaling through G proteins in platelets: To the integrins and beyond. Thromb Haemost 1997;78:581-9.
67. Offermanns S. Activation of platelet function through G protein- coupled receptors. Circ Res 2006;99:1293-304.
68. Hechler B, Leon C, Vial C, Vigne P, Frelin C, Cazenave JP, et al. The P2Y1 receptor is necessary for adenosine 5'-diphosphate- induced platelet aggregation. Blood 1998;92:152-9.
69. Ohlmann P, Laugwitz KL, Nurnberg B, Spicher K, Schultz G, Cazenave JP, et al. The human platelet ADP receptor activates Gi2 proteins. Biochem J 1995;312:775-9.
70. Cattaneo M, Zighetti ML, Lombardi R, Martinez C, Lecchi A, Conley PB, et al. Molecular bases of defective signal transduction in the platelet P2Y12 receptor of a patient with congenital bleeding. Proc Natl Acad Sci USA 2003;100:1978-83.
71. Kahn ML, Zheng YW, Huang W, Bigornia V, Zeng D, Moff S, et al. A dual thrombin receptor system for platelet activation. Nature 1998;394:690-4.
72. 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;64:1057-68.
73. Ishii K, Chen J, Ishii M, Koch WJ, Freedman NJ, Lefkowitz RJ, et al. Inhibition of thrombin receptor signaling by a Gprotein coupled receptor kinase. Functional specificity among G-protein coupled receptor kinases. J Biol Chem 1994;269: 1125-30.
74. De Candia E, Hall SW, Rutella S, Landolfi R, Andrews RK, De Cristofaro R. Binding of thrombin to glycoprotein Ib accelerates the hydrolysis of Par-1 on intact platelets. J Biol Chem 2001;276:4692-8.
75. Siller-Matula JM, Krumphuber J, Jilma B. Pharmacokinetic, pharmacodynamic and clinical profile of novel antiplatelet drugs targeting vascular diseases. Br J Pharmacol 2010;159: 502-17.
76. Woulfe D, Yang J, Prevost N, O'Brien PJ, Brass LF. Signal transduction during the initiation, extension and perpetuation of platelet plug formation. In: Michelson AD, editor. Platelets. London: Elsevier Science Academic Press, 2002:197-213.
77. Jhon DY, Lee HH, Park D, Lee CW, Lee KH, Yoo OJ, et al. Cloning, sequencing, purification, and Gq-dependent activation of phospholipase C-beta 3. J Biol Chem 1993;268: 6654-61.
78. Park D, Jhon DY, Kriz R, Knopf J, Rhee SG. Cloning, sequencing, expression, and Gq-independent activation of phospholipase C-beta 2. J Biol Chem 1992;267:16048-55.
79. Klages B, Brandt U, Simon MI, Schultz G, Offermanns S. Activation of G12/G13 results in shape change and Rho/Rhokinase- mediated myosin light chain phosphorylation in mouse platelets. J Cell Biol 1999;144:745-54.
80. Yang J, Wu J, Jiang H, Mortensen R, Austin S, Manning DR, et al. Signaling through Gi family members in platelets. Redundancy and specificity in the regulation of adenylyl cyclase and other effectors. J Biol Chem 2002;277:46035-42.
81. Cheng Y, Austin SC, Rocca B, Koller BH, Coffman TM, Grosser T, et al. Role of prostacyclin in the cardiovascular response to thromboxane A2. Science 2002;296:539-41.
82. Bevers EM, Comfurius P, Vanrijn JL, Hemker HC, Zwaal RF. Generation of prothrombin-converting activity and the exposure of phosphatidylserine at the outer surface of platelets. Eur J Biochem 1982;122:429-36.
83. Hato T, Pampori N, Shattil SJ. Complementary roles for receptor clustering and conformational change in the adhesive and signaling functions of integrin alphaIIb beta3. J Cell Biol 1998;141:1685-95.
84. Arnaout MA, Goodman SL, Xiong JP. Structure and mechanics of integrin-based cell adhesion. Curr Opin Cell Biol 2007; 19:495-507.
85. Calderwood DA, Fujioka Y, de Pereda JM, Garcia-Alvarez B, Nakamoto T, Margolis B, et al. Integrin beta cytoplasmic domain interactions with phosphotyrosine-binding domains: A structural prototype for diversity in integrin signaling. Proc Natl Acad Sci USA 2003;100:2272-7.
86. Calderwood DA, Yan BX, de Pereda JM, Alvarez BG, Fujioka Y, Liddington RC, et al. The phosphotyrosine binding-like domain of talin activates integrins. J Biol Chem 2002;277: 21749-58.
87. Ma YQ, Qin J, Wu CY, Plow EF. Kindlin-2 (Mig-2): A coactivator of beta(3) integrins. J Cell Biol 2008;181:439-46.
88. Banno A, Ginsberg MH. Integrin activation. Biochem Soc Trans 2008;36:229-34.
89. Di Paolo G, Pellegrini L, Letinic K, Cestra G, Zoncu R, Voronov S, et al. Recruitment and regulation of phosphatidylinositol phosphate kinase type 1 gamma by the FERM domain of talin. Nature 2002;420:85-9.
90. Lee HS, Lim CJ, Puzon-McLaughlin W, Shattil SJ, Ginsberg MH. RIAM activates integrins by linking talin to ras GTPase membrane-targeting sequences. J Biol Chem 2009;284:5119-27.
91. Harburger DS, Bouaouina M, Calderwood DA. Kindlin-1 and- 2 directly bind the C-terminal region of beta integrin cytoplasmic tails and exert integrin-specific activation effects. J Biol Chem 2009;284:11485-97.
92. Moser M, Nieswandt B, Ussar S, Pozgajova M, Fassler R. Kindlin-3 is essential for integrin activation and platelet aggregation. Nat Med 2008;14:325-30.
93. Nieswandt B, Moser M, Pleines I, Varga-Szabo D, Monkley S, Critchley D, et al. Loss of talin1 in platelets abrogates integrin activation, platelet aggregation, and thrombus formation in vitro and in vivo. J Exp Med 2007;204:3113-8.
94. Moser M, Legate KR, Zent R, Fassler R. The tail of integrins, talin, and kindlins. Science 2009;324:895-9.
95. Yang Z, Kollman JM, Pandi L, Doolittle RF. Crystal structure of native chicken fibrinogen at 2.7 A resolution. Biochemistry 2001;40:12515-23.
96. Bottcher RT, Lange A, Fassler R. How ILK and kindlins cooperate to orchestrate integrin signaling. Curr Opin Cell Biol 2009;21:670-5.
97. Lai-Cheong JE, Ussar S, Arita K, Hart IR, McGrath JA. Colocalization of kindlin-1 kindlin-2, and migfilin at keratinocyte focal adhesion and relevance to the pathophysiology of kindler syndrome. J Invest Dermatol 2008;128:2156-65.
98. Tu YZ, Wu S, Shi XH, Chen K, Wu CY. Migfilin and Mig- 2 link focal adhesions to filamin and the actin cytoskeleton and function in cell shape modulation. Cell 2003;113:37-47.
99. Prevost N, Woulfe DS, Jiang H, Stalker TJ, Marchese P, Ruggeri ZM, et al. Eph kinases and ephrins support thrombus growth and stability by regulating integrin outside-in signaling in platelets. Proc Natl Acad Sci USA 2005;102:9820-5.
100. Saltzman AJ, Mehran R, Hooper WC, Moses JW, Weisz G, Collins MB, et al. The relative effects of abciximab and tirofiban on platelet inhibition and C-reactive protein during coronary intervention. J Invasive Cardiol 2010;22:2-6.
101. Brener SJ. The benefits of platelet glycoprotein IIb/IIIa receptor inhibition during primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: Drugspecific or class effect? [comment] J Am Coll Cardiol 2009;53:1674-6. Comment on: J Am Coll Cardiol 2009;53: 1668-73.
102. George JN, Aster RH. Drug-induced thrombocytopenia: Pathogenesis, evaluation, and management. Hematology Am Soc Hematol Educ Program 2009;153-8.
103. Arehart E, Stitham J, Asselbergs FW, Douville K, MacKenzie T, Fetalvero KM, et al. Acceleration of cardiovascular disease by a dysfunctional prostacyclin receptor mutation: Potential implications for cyclooxygenase-2 inhibition. Circ Res 2008; 102:986-93.
104. Gambaryan S, Kobsar A, Rukoyatkina N, Herterich S, Geiger J, Smolenski A, et al. Thrombin and collagen induce a feedback inhibitory signaling pathway in platelets involving dissociation of the catalytic subunit of PKA from an NF-{kappa}B-I{kappa}B complex. J Biol Chem 2010;285: 18352-63.
105. Aszodi A, Pfeifer A, Ahmad M, Glauner M, Zhou XH, Ny L, et al. The vasodilator-stimulated phosphoprotein (VASP) is involved in cGMP- and cAMP-mediated inhibition of agonistinduced platelet aggregation, but is dispensable for smooth muscle function. EMBO J 1999;18:37-48.
106. Pula G, Schuh K, Nakayama K, Nakayama KI, Walter U, Poole AW. PKCdelta regulates collagen-induced platelet aggregation through inhibition of VASP-mediated filopodia formation. Blood 2006;108:4035-44.
107. Bauer M, Retzer M, Wilde JI, Maschberger P, Essler M, Aepfelbacher M, et al. Dichotomous regulation of myosin phosphorylation and shape change by Rho-kinase and calcium in intact human platelets. Blood 1999;94:1665-72.
108. Hathaway DR, Eaton CR, Adelstein RS. Regulation of human platelet myosin light chain kinase by the catalytic subunit of cyclic AMP-dependent protein kinase. Nature 1981;291: 252-6.
109. Walter U, Eigenthaler M, Geiger J, Reinhard M. Role of cyclic nucleotide-dependent protein kinases and their common substrate VASP in the regulation of human platelets. Adv Exp Med Biol 1993;344:237-49.
110. Naseem KM. eNOS, iNOS or no NOS, that is the question! [comment] J Thromb Haemost 2008;6:1373-5. Comment on: J Thromb Haemost 2008;8:1376-84.
111. Schlossmann J, Ammendola A, Ashman K, Zong X, Huber A, Neubauer G, et al. Regulation of intracellular calcium by a signalling complex of IRAG, IP3 receptor and cGMP kinase Ibeta. Nature 2000;404:197-201.
112. Trepakova ES, Cohen RA, Bolotina VM. Nitric oxide inhibits capacitative cation influx in human platelets by promoting sarcoplasmic/endoplasmic reticulum Ca2q-ATPase-dependent refilling of Ca2q stores. Circ Res 1999;84:201-9.
113. Wang GR, Zhu Y, Halushka PV, Lincoln TM, Mendelsohn ME. Mechanism of platelet inhibition by nitric oxide: In vivo phosphorylation of thromboxane receptor by cyclic GMPdependent protein kinase. Proc Natl Acad Sci USA 1998;95: 4888-93.
114. Maurice DH, Haslam RJ. Molecular basis of the synergistic inhibition of platelet function by nitrovasodilators and activators of adenylate cyclase: Inhibition of cyclic AMP breakdown by cyclic GMP. Mol Pharmacol 1990;37:671-81.
115. Pigazzi A, Heydrick S, Folli F, Benoit S, Michelson A, Loscalzo J. Nitric oxide inhibits thrombin receptor-activating peptide- induced phosphoinositide 3-kinase activity in human platelets. J Biol Chem 1999;274:14368-75.
116. Massberg S, Gruner S, Konrad I, Garcia Arguinzonis MI, Eigenthaler M, Hemler K, et al. Enhanced in vivo platelet adhesion in vasodilator-stimulated phosphoprotein (VASP)- deficient mice. Blood 2004;103:136-42.
117. Rajendran S, Chirkov YY. Platelet hyperaggregability: Impaired responsiveness to nitric oxide ('platelet NO resistance') as a therapeutic target. Cardiovasc Drugs Ther 2008; 22:193-203.
118. Lippi G, Favaloro EJ. The missing link between genotype, phenotype and clinics. Biochemia Medica 2009;19:137-45.
119. Zuern CS, Schwab M, Gawaz M, Geisler T. Platelet pharmacogenomics. J Thromb Haemost 2010;8:1147-58 wEpub 2010 Feb 1x.