Platelet P2Y12 receptors enhance signalling towards procoagulant activity and thrombin generation. A study with healthy subjects and patients at thrombotic risk

Thrombosis and Haemostasis

Volumn 93, Issue 6, 2005, Pages 1128-1136

  van der Meijden, Paola E J ^a,b   Feijge, Marion A H ^a,b   Giesen, Peter L A ^b   Huijberts, Maya ^c   van Raak, Lisette P M ^c   Heemskerk, Johan W M ^a,b  

^a MAASTRICHT UNIVERSITY   (Netherlands)

^b MAASTRICHT UNIVERSITY   (Netherlands)

^c MAASTRICHT UNIVERSITY MEDICAL CENTER   (Netherlands)

Author keywords

ADP; Coagulation; Platelets; Purinergic receptors

Indexed keywords

ADENOSINE DIPHOSPHATE; CALCIUM ION; CLOPIDOGREL; PADGEM PROTEIN; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLSERINE; PROTEINASE ACTIVATED RECEPTOR 1; PURINE P2Y12 RECEPTOR; THROMBIN; ANTITHROMBOCYTIC AGENT; DRUG DERIVATIVE; MEMBRANE PROTEIN; P2RY12 PROTEIN, HUMAN; PURINE P2 RECEPTOR; TICLOPIDINE;

ADULT; AGED; ARTERY THROMBOSIS; ARTICLE; BLOOD CLOTTING; CALCIUM SIGNALING; CELL ISOLATION; CLINICAL ARTICLE; CONTROLLED STUDY; FLOW CYTOMETRY; HUMAN; HUMAN CELL; NON INSULIN DEPENDENT DIABETES MELLITUS; PRIORITY JOURNAL; RECEPTOR INTRINSIC ACTIVITY; SIGNAL TRANSDUCTION; STROKE; THROMBOCYTE ACTIVATION; THROMBOCYTE AGGREGATION; BIOSYNTHESIS; BLOOD; CASE CONTROL STUDY; CEREBROVASCULAR ACCIDENT; DRUG EFFECT; IN VITRO STUDY; METABOLISM; MIDDLE AGED; THROMBOCYTE; THROMBOSIS;

ADENOSINE DIPHOSPHATE; ADULT; AGED; BLOOD PLATELETS; CALCIUM SIGNALING; CASE-CONTROL STUDIES; CEREBROVASCULAR ACCIDENT; DIABETES MELLITUS, TYPE 2; HUMANS; MEMBRANE PROTEINS; MIDDLE AGED; PHOSPHATIDYLSERINES; PLATELET AGGREGATION INHIBITORS; RECEPTORS, PURINERGIC P2; THROMBIN; THROMBOSIS; TICLOPIDINE;

EID: 20444503923     PISSN: 03406245     EISSN: None     Source Type: Journal    
DOI: 10.1160/TH04-09-0597     Document Type: Article

References (39)

1. Béguin S, Kumar R. Thrombin, fibrin and platelets, a resonance loop in which von Willebrand factor is a necessary link. Thromb Haemost 1997; 78: 590-4.
2. Monroe DM, Hoffman M, Roberts HR. Platelets and thrombin generation. Arterioscler Thromb Vasc Biol 2002; 22: 1381-9.
3. Heemskerk JWM, Bevers EM, Lindhout T. Platelet activation and blood coagulation. Thromb Haemost 2002; 88: 186-93.
4. Bevers EM, Comfurius P, van Rijn JLML et al. Generation of prothrombin-converting activity and the exposure of phosphatidylserine at the outer surface of platelets. Eur J Biochem 1982; 122: 429-36.
5. Coughlin SR. Thrombin signalling and protease-activated receptors. Nature 2000; 407: 258-64.
6. 2+-mobilizing potency of a-thrombin and thrombin-receptor-activating peptide on human platelets. Eur J Biochem 1997; 249: 547-55.
7. Andersen H, Greenberg DL, Fujikawa K et al. Protease-activated receptor 1 is the primary mediator of thrombin-stimulated platelet procoagulant activity. Proc Natl Acad Sci USA 1999; 96: 11189-93.
8. Gachet C, Hechler B, Léon C et al. Activation of ADP receptors and platelet function. Thromb Haemost 1997; 78: 271-5.
9. Kunapuli SP, Dorsam RT, Kim S et al. Platelet purinergic receptors. Curr Opin Pharmacol 2003; 3: 175-80.
10. Jin J, Kunapuli SP. Coactivation of two different G protein-coupled receptors is essential for ADP-induced platelet aggregation. Proc Natl Acad Sci USA 1998; 95: 8070-4.
11. Hollopeter G, Jantzen HM, Vincent D et al. Identification of the platelet ADP receptor targeted by antithrombotic drugs. Nature 2001; 409: 202-8.
12. Remijn JA, Wu YP, Heninga EH et al. Role of ADP receptor P2Y12 in platelet adhesion and thrombus formation in flowing blood. Arterioscler Thromb Vasc Biol 2002; 22: 686-91.
13. Siljander PRM, Munnix ICA, Smethurst PA et al. Platelet receptor interplay regulates collagen-induced thrombus formation in flowing human blood. Blood 2004; 103: 1333-41.
14. Keularts IM, van Gorp RM, Feijge MA et al. a2A-adrenergic receptor stimulation potentiates calcium release in platelets by modulating cAMP levels. J Biol Chem 2000; 275: 1763-72.
15. Hirsch E, Bosco O, Tropel P et al. Resistance to thromboembolism in PI3Kg-deficient mice. FASEB J 2001; 15: 2019-21.
16. Kauffenstein G, Bergmeier W, Eckly A et al. The P2Y12 receptor induces platelet aggregation through weak activation of the aIIbb3 integrin: phosphoinositide 3-kinase-dependent mechanism. FEBS Lett 2001; 505: 281-90.
17. Weiss HJ, Lages B. Platelet prothrombinase activity and intracellular calcium responses in patients with storage pool deficiency, glycoprotein IIb-IIIa deficiency, or impaired platelet coagulant activity. Blood 1997; 89: 1599-611.
18. Léon C, Ravanat C, Freund M et al. Differential involvement of the P2Y1 and P2Y12 receptors in platelet procoagulant activity. Arterioscler Thromb Vasc Biol 2003; 23: 1941-7.
19. Vanschoonbeek K, Feijge MAH, van Kampen RJ et al. Initiating and potentiating role of platelets in tissue factor-induced thrombin generation in the presence of plasma: subject-dependent variation in thrombogram characteristics. J Thromb Haemost 2004; 2: 476-84.
20. Dorsam RT, Tuluc M, Kunapuli SP. Role of protease-activated and ADP receptor subtypes in thrombin generation on human platelets. J Thromb Haemost 2004; 2: 804-12.
21. Thiagarajan P, Tait JF. Collagen-induced exposure of anionic phospholipid in platelets and platelet-derived microparticles. J Biol Chem 1991; 266: 24302-7.
22. Savi P, Pereillo JM, Uzabiaga MF et al. Identification and biological activity of the active metabolite of clopidogrel. Thromb Haemost 2000; 84: 891-6.
23. Cattaneo M. The platelet P2Y receptors as targets for new antithrombotic drugs. J Thromb Haemost 2003; 1: 1133-5.
24. Conley PB, Delaney SM. Scientific and therapeutic insights into the role of the platelet P2Y12 receptor in thrombosis. Curr Opin Hematol 2003; 10: 333-8.
25. Lau WC, Gurbel PA, Watkins PB et al. Contribution of hepatic cytochrome P450 3A4 metabolic activity to the phenomenon of clopidogrel resistance. Circulation 2004; 109: 166-71.
26. Vanschoonbeek K, Feijge MAH, Keuren JF et al. Thrombin-induced hyperactivity of platelets of young stroke patients. Thromb Haemost 2002; 88: 931-7.
27. Carr ME. Diabetes mellitus: a hypercoagulable state. J Diabetes Complications 2001; 15: 44-54.
28. Hemker HC, Giesen PL, Ramjee M et al. The thrombogram: monitoring thrombin generation in platelet-rich plasma. Thromb Haemost 2000; 83: 589-91.
29. Hemker HC, Giesen P, Al Dieri R et al. Calibrated automated thrombin generation measurement in clotting plasma. Pathophysiol Haemost Thromb 2003; 33: 4-15.
30. Feijge MAH, van Pampus EC, Lacabaratz-Porret C et al. Inter-individual variability in Ca2+ signalling in platelets from healthy volunteers. Br J Haematol 1998; 102: 850-9.
31. Curvers J, van Pampus ECM, Feijge MAH et al. Decreased responsiveness and development of activation markers of platelets stored in plasma. Transfusion 2004; 44: 49-58.
32. Sage SO, Yamoah EH, Heemskerk JWM. The roles of P2X1 and P2TAC receptors in ADP-evoked calcium signalling in human platelets. Cell Calcium 2000; 28: 119-26.
33. Storey RF, Sanderson HM, White AE et al. The central role of the P2T receptor in amplification of human platelet activation, secretion and procoagulant activity. Br J Haematol 2000; 110: 925-34.
34. 2+ responses and platelet aggregation by the P2Y12 receptor antagonists AR-C69931MX and clopidogrel is enhanced by prostaglandin E1. Cell Calcium 2004; 35: 39-46.
35. Hardy AR, Jones ML, Mundell SJ et al. Reciprocal cross-talk between P2Y1 and P2Y12 receptors at the level of calcium signaling in human platelets. Blood 2004; 104: 1745-52.
36. Aleil B, Ravanat C, Cazerave JP et al. Flow cytometric detection of intraplatelet VASP phosphorylation for the detection of clopidogrel resistance in patients with ischemic cardiovascular disease. J Thromb Haemost 2005; 3: 85-92.
37. Gurbel PA, Bliden KP. Durability of platelet inhibition by clopidogrel. Am J Cardiol 2003; 91: 1123-5.
38. Muller I, Besta F, Schulz C et al. Prevalence of clopidogrel non-responders among patients with stable angina pectoris scheduled for elective coronary stent placement. Thromb Haemost 2003; 89: 783-7.
39. Nawarskas JJ. Clopidogrel-statin interaction. Cardiol Rev 2004; 12: 236-9.