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Adenosine and blood platelets

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Abstract

Adenosine is an important regulatory metabolite and an inhibitor of platelet activation. Adenosine released from different cells or generated through the activity of cell-surface ectoenzymes exerts its effects through the binding of four different G-protein-coupled adenosine receptors. In platelets, binding of A2 subtypes (A2A or A2B) leads to consequent elevation of intracellular cyclic adenosine monophosphate, an inhibitor of platelet activation. The significance of this ligand and its receptors for platelet activation is addressed in this review, including how adenosine metabolism and its A2 subtype receptors impact the expression and activity of adenosine diphosphate receptors. The expression of A2 adenosine receptors is induced by conditions such as oxidative stress, a hallmark of aging. The effect of adenosine receptors on platelet activation during aging is also discussed, as well as potential therapeutic applications.

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References

  1. Bours MJ, Swennen EL, Di Virgilio F, Cronstein BN, Dagnelie PC (2006) Adenosine 5′-triphosphate and adenosine as endogenous signaling molecules in immunity and inflammation. Pharmacol Ther 112(2):358–404

    Article  PubMed  CAS  Google Scholar 

  2. Linden J (2005) Adenosine in tissue protection and tissue regeneration. Mol Pharmacol 67(5):1385–1387

    Article  PubMed  CAS  Google Scholar 

  3. Fredholm BB (2007) Adenosine, an endogenous distress signal, modulates tissue damage and repair. Cell Death Differ 14(7):1315–1323

    Article  PubMed  CAS  Google Scholar 

  4. Sauer H, Hescheler J, Wartenberg M (2000) Mechanical strain-induced Ca(2+) waves are propagated via ATP release and purinergic receptor activation. Am J Physiol Cell Physiol 279(2):C295–C307

    PubMed  CAS  Google Scholar 

  5. Van der Wijk T, De Jonge HR, Tilly BC (1999) Osmotic cell swelling-induced ATP release mediates the activation of extracellular signal-regulated protein kinase (Erk)-1/2 but not the activation of osmo-sensitive anion channels. Biochem J 343(Pt 3):579–586

    Article  PubMed  Google Scholar 

  6. Rump LC, Bohmann C, Schwertfeger E, Krumme B, von Kugelgen I, Schollmeyer P (1996) Extracellular ATP in the human kidney: mode of release and vascular effects. J Auton Pharmacol 16(6):371–375

    Article  PubMed  CAS  Google Scholar 

  7. Born GV, Kratzer MA (1984) Source and concentration of extracellular adenosine triphosphate during haemostasis in rats, rabbits and man. J Physiol 354:419–429

    PubMed  CAS  Google Scholar 

  8. Kaczmarek E, Koziak K, Sevigny J, Siegel JB, Anrather J, Beaudoin AR, Bach FH, Robson SC (1996) Identification and characterization of CD39/vascular ATP diphosphohydrolase. J Biol Chem 271(51):33116–33122

    Article  PubMed  CAS  Google Scholar 

  9. Wang TF, Guidotti G (1996) CD39 is an ecto-(Ca2+, Mg2+)-apyrase. J Biol Chem 271(17):9898–9901

    Article  PubMed  CAS  Google Scholar 

  10. Eltzschig HK, Ibla JC, Furuta GT, Leonard MO, Jacobson KA, Enjyoji K, Robson SC, Colgan SP (2003) Coordinated adenine nucleotide phosphohydrolysis and nucleoside signaling in posthypoxic endothelium: role of ectonucleotidases and adenosine A2B receptors. J Exp Med 198(5):783–796

    Article  PubMed  CAS  Google Scholar 

  11. Goding JW, Grobben B, Slegers H (2003) Physiological and pathophysiological functions of the ecto-nucleotide pyrophosphatase/phosphodiesterase family. Biochim Biophys Acta 1638(1):1–19

    PubMed  CAS  Google Scholar 

  12. Eckle T, Krahn T, Grenz A, Kohler D, Mittelbronn M, Ledent C, Jacobson MA, Osswald H, Thompson LF, Unertl K, Eltzschig HK (2007) Cardioprotection by ecto-5′-nucleotidase (CD73) and A2B adenosine receptors. Circulation 115(12):1581–1590

    Article  PubMed  CAS  Google Scholar 

  13. Gines S, Ciruela F, Burgueno J, Casado V, Canela EI, Mallol J, Lluis C, Franco R (2001) Involvement of caveolin in ligand-induced recruitment and internalization of A(1) adenosine receptor and adenosine deaminase in an epithelial cell line. Mol Pharmacol 59(5):1314–1323

    PubMed  CAS  Google Scholar 

  14. Kittel A, Kiss AL, Mullner N, Matko I, Sperlagh B (2005) Expression of NTPDase1 and caveolins in human cardiovascular disease. Histochem Cell Biol 124(1):51–59

    Article  PubMed  CAS  Google Scholar 

  15. Kittel A, Kaczmarek E, Sevigny J, Lengyel K, Csizmadia E, Robson SC (1999) CD39 as a caveolar-associated ectonucleotidase. Biochem Biophys Res Commun 262(3):596–599

    Article  PubMed  CAS  Google Scholar 

  16. Lasley RD, Narayan P, Uittenbogaard A, Smart EJ (2000) Activated cardiac adenosine A(1) receptors translocate out of caveolae. J Biol Chem 275(6):4417–4421

    Article  PubMed  CAS  Google Scholar 

  17. Sitaraman SV, Wang L, Wong M, Bruewer M, Hobert M, Yun CH, Merlin D, Madara JL (2002) The adenosine 2b receptor is recruited to the plasma membrane and associates with E3KARP and Ezrin upon agonist stimulation. J Biol Chem 277(36):33188–33195

    Article  PubMed  CAS  Google Scholar 

  18. Matsuoka I, Ohkubo S (2004) ATP- and adenosine-mediated signaling in the central nervous system: adenosine receptor activation by ATP through rapid and localized generation of adenosine by ecto-nucleotidases. J Pharmacol Sci 94(2):95–99

    Article  PubMed  CAS  Google Scholar 

  19. Decking UK, Schlieper G, Kroll K, Schrader J (1997) Hypoxia-induced inhibition of adenosine kinase potentiates cardiac adenosine release. Circ Res 81(2):154–164

    PubMed  CAS  Google Scholar 

  20. Lutz PL, Prentice HM (2002) Sensing and responding to hypoxia, molecular and physiological mechanisms. Integr Comp Biol 42(3):463–468

    Article  PubMed  CAS  Google Scholar 

  21. Baldwin SA, Beal PR, Yao SY, King AE, Cass CE, Young JD (2004) The equilibrative nucleoside transporter family, SLC29. Pflugers Arch 447(5):735–743

    Article  PubMed  CAS  Google Scholar 

  22. Gray JH, Owen RP, Giacomini KM (2004) The concentrative nucleoside transporter family, SLC28. Pflugers Arch 447(5):728–734

    Article  PubMed  CAS  Google Scholar 

  23. Griffith DA, Jarvis SM (1996) Nucleoside and nucleobase transport systems of mammalian cells. Biochim Biophys Acta 1286(3):153–181

    PubMed  CAS  Google Scholar 

  24. Heptinstall S, Johnson A, Glenn JR, White AE (2005) Adenine nucleotide metabolism in human blood–important roles for leukocytes and erythrocytes. J Thromb Haemost 3(10):2331–2339

    Article  PubMed  CAS  Google Scholar 

  25. Stafford NP, Pink AE, White AE, Glenn JR, Heptinstall S (2003) Mechanisms involved in adenosine triphosphate–induced platelet aggregation in whole blood. Arterioscler Thromb Vasc Biol 23(10):1928–1933

    Article  PubMed  CAS  Google Scholar 

  26. Dwyer KM, Robson SC, Nandurkar HH, Campbell DJ, Gock H, Murray-Segal LJ, Fisicaro N, Mysore TB, Kaczmarek E, Cowan PJ, d’Apice AJ (2004) Thromboregulatory manifestations in human CD39 transgenic mice and the implications for thrombotic disease and transplantation. J Clin Invest 113(10):1440–1446

    PubMed  CAS  Google Scholar 

  27. Marcus AJ, Safier LB, Hajjar KA, Ullman HL, Islam N, Broekman MJ, Eiroa AM (1991) Inhibition of platelet function by an aspirin-insensitive endothelial cell ADPase. Thromboregulation by endothelial cells. J Clin Invest 88(5):1690–1696

    Article  PubMed  CAS  Google Scholar 

  28. Marcus AJ, Safier LB, Broekman MJ, Islam N, Fliessbach JH, Hajjar KA, Kaminski WE, Jendraschak E, Silverstein RL, von Schacky C (1995) Thrombosis and inflammation as multicellular processes: significance of cell-cell interactions. Thromb Haemost 74(1):213–217

    PubMed  CAS  Google Scholar 

  29. Sevigny J, Sundberg C, Braun N, Guckelberger O, Csizmadia E, Qawi I, Imai M, Zimmermann H, Robson SC (2002) Differential catalytic properties and vascular topography of murine nucleoside triphosphate diphosphohydrolase 1 (NTPDase1) and NTPDase2 have implications for thromboregulation. Blood 99(8):2801–2809

    Article  PubMed  CAS  Google Scholar 

  30. Yegutkin GG (2008) Nucleotide- and nucleoside-converting ectoenzymes: important modulators of purinergic signalling cascade. Biochim Biophys Acta 1783(5):673–694

    Article  PubMed  CAS  Google Scholar 

  31. Fredholm BB, IJ AP, Jacobson KA, Klotz KN, Linden J (2001) International union of pharmacology. XXV. Nomenclature and classification of adenosine receptors. Pharmacol Rev 53(4):527–552

    PubMed  CAS  Google Scholar 

  32. Dixon A, Gubitz AK, Sirinathsinghji DJ, Richardson PJ, Freeman TC (1996) Tissue distribution of adenosine receptor mRNAs in the rat. Br J Pharmacol 118:1461–1468

    PubMed  CAS  Google Scholar 

  33. Huang S, Apasov S, Koshiba M, Sitkovsky M (1997) Role of A2a extracellular adenosine receptor-mediated signaling in adenosine-mediated inhibition of T-cell activation and expansion. Blood 90(4):1600–1610

    PubMed  CAS  Google Scholar 

  34. Cronstein BN, Daguma L, Nichols D, Hutchison AJ, Williams M (1990) The adenosine/neutrophil paradox resolved: human neutrophils possess both A1 and A2 receptors that promote chemotaxis and inhibit O2 generation, respectively. J Clin Invest 85(4):1150–1157

    Article  PubMed  CAS  Google Scholar 

  35. Salama SE, Haslam RJ (1981) Subcellular distribution of cyclic AMP-dependent protein kinase activity and of cyclic AMP-binding proteins in human platelets. Modification by Ca2+-dependent proteolysis. FEBS Lett 130(2):230–234

    Article  PubMed  CAS  Google Scholar 

  36. Ledent C, Vaugeois JM, Schiffmann SN, Pedrazzini T, El Yacoubi M, Vanderhaeghen JJ, Costentin J, Heath JK, Vassart G, Parmentier M (1997) Aggressiveness, hypoalgesia and high blood pressure in mice lacking the adenosine A2a receptor. Nature 388(6643):674–678

    Article  PubMed  CAS  Google Scholar 

  37. Martin PL, Ueeda M, Olsson RA (1993) 2-Phenylethoxy-9-methyladenine: an adenosine receptor antagonist that discriminates between A2 adenosine receptors in the aorta and the coronary vessels from the guinea pig. J Pharmacol Exp Ther 265(1):248–253

    PubMed  CAS  Google Scholar 

  38. Conti A, Monopoli A, Gamba M, Borea PA, Ongini E (1993) Effects of selective A1 and A2 adenosine receptor agonists on cardiovascular tissues. Naunyn Schmiedebergs Arch Pharmacol 348(1):108–112

    Article  PubMed  CAS  Google Scholar 

  39. Yang D, Zhang Y, Nguyen HG, Koupenova M, Chauhan AK, Makitalo M, Jones MR, St Hilaire C, Seldin DC, Toselli P, Lamperti E, Schreiber BM, Gavras H, Wagner DD, Ravid K (2006) The A2B adenosine receptor protects against inflammation and excessive vascular adhesion. J Clin Invest 116(7):1913–1923

    Article  PubMed  CAS  Google Scholar 

  40. Gachet C (2008) P2 receptors, platelet function and pharmacological implications. Thromb Haemost 99(3):466–472

    PubMed  CAS  Google Scholar 

  41. Jennings LK (2009) Mechanisms of platelet activation: need for new strategies to protect against platelet-mediated atherothrombosis. Thromb Haemost 102(2):248–257

    PubMed  CAS  Google Scholar 

  42. Feletou M, Vanhoutte PM, Verbeuren TJ (2010) The thromboxane/endoperoxide receptor (TP): the common villain. J Cardiovasc Pharmacol 55(4):317–332

    Article  PubMed  CAS  Google Scholar 

  43. Macaulay TE, Allen C, Ziada KM (2010) Thrombin receptor antagonism -the potential of antiplatelet medication SCH 530348. Expert Opin Pharmacother 11(6):1015–1022

    Article  PubMed  CAS  Google Scholar 

  44. Li Z, Delaney MK, O’Brien KA, Du X (2010) Signaling during platelet adhesion and activation. Arterioscler Thromb Vasc Biol 30(12):2341–2349

    Article  PubMed  CAS  Google Scholar 

  45. Smyth SS, Woulfe DS, Weitz JI, Gachet C, Conley PB, Goodman SG, Roe MT, Kuliopulos A, Moliterno DJ, French PA, Steinhubl SR, Becker RC (2009) G-protein-coupled receptors as signaling targets for antiplatelet therapy. Arterioscler Thromb Vasc Biol 29(4):449–457

    Article  PubMed  CAS  Google Scholar 

  46. Offermanns S (2006) Activation of platelet function through G protein-coupled receptors. Circ Res 99(12):1293–1304

    Article  PubMed  CAS  Google Scholar 

  47. Crittenden JR, Bergmeier W, Zhang Y, Piffath CL, Liang Y, Wagner DD, Housman DE, Graybiel AM (2004) CalDAG-GEFI integrates signaling for platelet aggregation and thrombus formation. Nat Med 10(9):982–986

    Article  PubMed  CAS  Google Scholar 

  48. Hantgan RR, Stahle MC, Lord ST (2010) Dynamic regulation of fibrinogen: integrin alphaIIbbeta3 binding. Biochemistry 49(43):9217–9225

    Article  PubMed  CAS  Google Scholar 

  49. Weisel JW (2005) Fibrinogen and fibrin. Adv Protein Chem 70:247–299

    Article  PubMed  CAS  Google Scholar 

  50. Mosesson MW (2005) Fibrinogen and fibrin structure and functions. J Thromb Haemost 3(8):1894–1904

    Article  PubMed  CAS  Google Scholar 

  51. Mangin P, Yuan Y, Goncalves I, Eckly A, Freund M, Cazenave JP, Gachet C, Jackson SP, Lanza F (2003) Signaling role for phospholipase C gamma 2 in platelet glycoprotein Ib alpha calcium flux and cytoskeletal reorganization. Involvement of a pathway distinct from FcR gamma chain and Fc gamma RIIA. J Biol Chem 278(35):32880–32891

    Article  PubMed  CAS  Google Scholar 

  52. Christodoulides N, Feng S, Resendiz JC, Berndt MC, Kroll MH (2001) Glycoprotein Ib/IX/V binding to the membrane skeleton maintains shear-induced platelet aggregation. Thromb Res 102(2):133–142

    Article  PubMed  CAS  Google Scholar 

  53. Jarvis SM (1986) Nitrobenzylthioinosine-sensitive nucleoside transport system: mechanism of inhibition by dipyridamole. Mol Pharmacol 30(6):659–665

    PubMed  CAS  Google Scholar 

  54. Harker LA, Kadatz RA (1983) Mechanism of action of dipyridamole. Thromb Res Suppl 4:39–46

    Article  PubMed  CAS  Google Scholar 

  55. Moncada S (2006) Adventures in vascular biology: a tale of two mediators. Philos Trans R Soc Lond B Biol Sci 361(1469):735–759

    Article  PubMed  CAS  Google Scholar 

  56. Strong JCMFGCHIKMJSP (1994) Adenosine receptor classification: quo vadimus? Nucleosides Nucleotides Nucleic Acids 13(9):1953–1976

    Article  Google Scholar 

  57. Collis MG, Hourani SM (1993) Adenosine receptor subtypes. Trends Pharmacol Sci 14(10):360–366

    Article  PubMed  CAS  Google Scholar 

  58. van Galen PJ, Stiles GL, Michaels G, Jacobson KA (1992) Adenosine A1 and A2 receptors: structure–function relationships. Med Res Rev 12(5):423–471

    Article  PubMed  Google Scholar 

  59. Paul S, Feoktistov I, Hollister AS, Robertson D, Biaggioni I (1990) Adenosine inhibits the rise in intracellular calcium and platelet aggregation produced by thrombin: evidence that both effects are coupled to adenylate cyclase. Mol Pharmacol 37(6):870–875

    PubMed  CAS  Google Scholar 

  60. Dionisotti S, Ferrara S, Molta C, Zocchi C, Ongini E (1996) Labeling of A2A adenosine receptors in human platelets by use of the new nonxanthine antagonist radioligand [3 H]SCH 58261. J Pharmacol Exp Ther 278(3):1209–1214

    PubMed  CAS  Google Scholar 

  61. Wang H, Zhang W, Zhu C, Bucher C, Blazar BR, Zhang C, Chen JF, Linden J, Wu C, Huo Y (2009) Inactivation of the adenosine A2A receptor protects apolipoprotein E-deficient mice from atherosclerosis. Arterioscler Thromb Vasc Biol 29(7):1046–1052

    Article  PubMed  CAS  Google Scholar 

  62. Cooper JA, Hill SJ, Alexander SP, Rubin PC, Horn EH (1995) Adenosine receptor-induced cyclic AMP generation and inhibition of 5-hydroxytryptamine release in human platelets. Br J Clin Pharmacol 40(1):43–50

    PubMed  CAS  Google Scholar 

  63. Varani K, Portaluppi F, Merighi S, Ongini E, Belardinelli L, Borea PA (1999) Caffeine alters A2A adenosine receptors and their function in human platelets. Circulation 99(19):2499–2502

    PubMed  CAS  Google Scholar 

  64. Linden MD, Barnard MR, Frelinger AL, Michelson AD, Przyklenk K (2008) Effect of adenosine A2 receptor stimulation on platelet activation-aggregation: differences between canine and human models. Thromb Res 121(5):689–698

    Article  PubMed  CAS  Google Scholar 

  65. Hourani SM (1996) Purinoceptors and platelet aggregation. J Auton Pharmacol 16(6):349–352

    Article  PubMed  CAS  Google Scholar 

  66. Yang D, Chen H, Koupenova M, Carroll SH, Eliades A, Freedman JE, Toselli P, Ravid K (2010) A new role for the A2b adenosine receptor in regulating platelet function. J Thromb Haemost 8(4):817–827

    Article  PubMed  CAS  Google Scholar 

  67. Amisten S, Braun OO, Bengtsson A, Erlinge D (2008) Gene expression profiling for the identification of G-protein coupled receptors in human platelets. Thromb Res 122(1):47–57

    Article  PubMed  CAS  Google Scholar 

  68. Yang D, Koupenova M, McCrann DJ, Kopeikina KJ, Kagan HM, Schreiber BM, Ravid K (2008) The A2b adenosine receptor protects against vascular injury. Proc Natl Acad Sci USA 105(2):792–796

    Article  PubMed  CAS  Google Scholar 

  69. St Hilaire C, Koupenova M, Carroll SH, Smith BD, Ravid K (2008) TNF-alpha upregulates the A2B adenosine receptor gene: the role of NAD(P)H oxidase 4. Biochem Biophys Res Commun 375(3):292–296

    Article  PubMed  CAS  Google Scholar 

  70. Fabre JE, Nguyen M, Latour A, Keifer JA, Audoly LP, Coffman TM, Koller BH (1999) Decreased platelet aggregation, increased bleeding time and resistance to thromboembolism in P2Y1-deficient mice. Nat Med 5(10):1199–1202

    Article  PubMed  CAS  Google Scholar 

  71. Hechler B, Leon C, Vial C, Vigne P, Frelin C, Cazenave JP, Gachet C (1998) The P2Y1 receptor is necessary for adenosine 5′-diphosphate-induced platelet aggregation. Blood 92(1):152–159

    PubMed  CAS  Google Scholar 

  72. Leon C, Hechler B, Freund M, Eckly A, Vial C, Ohlmann P, Dierich A, LeMeur M, Cazenave JP, Gachet C (1999) Defective platelet aggregation and increased resistance to thrombosis in purinergic P2Y(1) receptor-null mice. J Clin Invest 104(12):1731–1737

    Article  PubMed  CAS  Google Scholar 

  73. Hechler B, Zhang Y, Eckly A, Cazenave JP, Gachet C, Ravid K (2003) Lineage-specific overexpression of the P2Y1 receptor induces platelet hyper-reactivity in transgenic mice. J Thromb Haemost 1(1):155–163

    Article  PubMed  CAS  Google Scholar 

  74. Weseler AR, Bast A (2010) Oxidative stress and vascular function: implications for pharmacologic treatments. Curr Hypertens Rep 12(3):154–161

    Article  PubMed  CAS  Google Scholar 

  75. Hirooka Y, Sagara Y, Kishi T, Sunagawa K (2010) Oxidative stress and central cardiovascular regulation. - pathogenesis of hypertension and therapeutic aspects. Circ J 74(5):827–835

    Article  PubMed  CAS  Google Scholar 

  76. Leopold JA, Loscalzo J (2009) Oxidative risk for atherothrombotic cardiovascular disease. Free Radic Biol Med 47(12):1673–1706

    Article  PubMed  CAS  Google Scholar 

  77. Gao L, Mann GE (2009) Vascular NAD(P)H oxidase activation in diabetes: a double-edged sword in redox signalling. Cardiovasc Res 82(1):9–20

    Article  PubMed  CAS  Google Scholar 

  78. Romano AD, Serviddio G, de Matthaeis A, Bellanti F, Vendemiale G (2010) Oxidative stress and aging. J Nephrol 23(Suppl 15):S29–S36

    PubMed  Google Scholar 

  79. Haigis MC, Yankner BA (2010) The aging stress response. Mol Cell 40(2):333–344

    Article  PubMed  CAS  Google Scholar 

  80. Oliveira BF, Nogueira-Machado JA, Chaves MM (2010) The role of oxidative stress in the aging process. ScientificWorldJournal 10:1121–1128

    Article  PubMed  CAS  Google Scholar 

  81. Fitzgerald DJ, Roy L, Catella F, FitzGerald GA (1986) Platelet activation in unstable coronary disease. N Engl J Med 315(16):983–989

    Article  PubMed  CAS  Google Scholar 

  82. van Kooten F, Ciabattoni G, Koudstaal PJ, Dippel DW, Patrono C (1999) Increased platelet activation in the chronic phase after cerebral ischemia and intracerebral hemorrhage. Stroke 30(3):546–549

    Article  PubMed  Google Scholar 

  83. Gurbel PA, Serebruany VL (2002) Adhesion molecules, platelet activation, and cardiovascular risk. Am Heart J 143(2):196–198

    Article  PubMed  Google Scholar 

  84. McCabe DJ, Harrison P, Sidhu PS, Brown MM, Machin SJ (2004) Circulating reticulated platelets in the early and late phases after ischaemic stroke and transient ischaemic attack. Br J Haematol 126(6):861–869

    Article  PubMed  Google Scholar 

  85. Joseph R, Riddle JM, Welch KM, D’Andrea G (1989) Platelet ultrastructure and secretion in acute ischemic stroke. Stroke 20(10):1316–1319

    Article  PubMed  CAS  Google Scholar 

  86. Ajzenberg N, Talab AT, Masse JM, Drouin A, Jondeau K, Kobeiter H, Baruch D, Cramer EM (2005) Platelet shape change and subsequent glycoprotein redistribution in human stenosed arteries. Platelets 16(1):13–18

    Article  PubMed  CAS  Google Scholar 

  87. Croce K, Libby P (2007) Intertwining of thrombosis and inflammation in atherosclerosis. Curr Opin Hematol 14(1):55–61

    Article  PubMed  CAS  Google Scholar 

  88. Ross R (1999) Atherosclerosis–an inflammatory disease. N Engl J Med 340(2):115–126

    Article  PubMed  CAS  Google Scholar 

  89. Bastyr EJ 3rd, Kadrofske MM, Vinik AI (1990) Platelet activity and phosphoinositide turnover increase with advancing age. Am J Med 88(6):601–606

    Article  PubMed  CAS  Google Scholar 

  90. Gleerup G, Winther K (1995) The effect of ageing on platelet function and fibrinolytic activity. Angiology 46(8):715–718

    Article  PubMed  CAS  Google Scholar 

  91. Peng J, Friese P, Heilmann E, George JN, Burstein SA, Dale GL (1994) Aged platelets have an impaired response to thrombin as quantitated by P-selectin expression. Blood 83(1):161–166

    PubMed  CAS  Google Scholar 

  92. Origlia C, Pescarmona G, Capizzi A, Cogotti S, Gambino R, Cassader M, Benso A, Granata R, Martina V (2004) Platelet cGMP inversely correlates with age in healthy subjects. J Endocrinol Investig 27(2):RC1–RC4

    CAS  Google Scholar 

  93. Jayachandran M, Karnicki K, Miller RS, Owen WG, Korach KS, Miller VM (2005) Platelet characteristics change with aging: role of estrogen receptor beta. J Gerontol A Biol Sci Med Sci 60(7):815–819

    Article  PubMed  Google Scholar 

  94. Gilstad JR, Gurbel PA, Andersen RE (2009) Relationship between age and platelet activation in patients with stable and unstable angina. Arch Gerontol Geriatr 48(2):155–159

    Article  PubMed  CAS  Google Scholar 

  95. Przyklenk K, Whittaker P (2000) Brief antecedent ischemia enhances recombinant tissue plasminogen activator-induced coronary thrombolysis by adenosine-mediated mechanism. Circulation 102(1):88–95

    PubMed  CAS  Google Scholar 

  96. Hata K, Whittaker P, Kloner RA, Przyklenk K (1999) Brief myocardial ischemia attenuates platelet thrombosis in remote, damaged, and stenotic carotid arteries. Circulation 100(8):843–848

    PubMed  CAS  Google Scholar 

  97. Przyklenk K, Whittaker P (2005) In vitro platelet responsiveness to adenosine-mediated “preconditioning” is age-dependent. J Thromb Thrombolysis 19(1):5–10

    Article  PubMed  CAS  Google Scholar 

  98. Robson SC, Kaczmarek E, Siegel JB, Candinas D, Koziak K, Millan M, Hancock WW, Bach FH (1997) Loss of ATP diphosphohydrolase activity with endothelial cell activation. J Exp Med 185(1):153–163

    Article  PubMed  CAS  Google Scholar 

  99. Enjyoji K, Sevigny J, Lin Y, Frenette PS, Christie PD, Esch JS 2nd, Imai M, Edelberg JM, Rayburn H, Lech M, Beeler DL, Csizmadia E, Wagner DD, Robson SC, Rosenberg RD (1999) Targeted disruption of cd39/ATP diphosphohydrolase results in disordered hemostasis and thromboregulation. Nat Med 5(9):1010–1017

    Article  PubMed  CAS  Google Scholar 

  100. Kohler D, Eckle T, Faigle M, Grenz A, Mittelbronn M, Laucher S, Hart ML, Robson SC, Muller CE, Eltzschig HK (2007) CD39/ectonucleoside triphosphate diphosphohydrolase 1 provides myocardial protection during cardiac ischemia/reperfusion injury. Circulation 116(16):1784–1794

    Article  PubMed  CAS  Google Scholar 

  101. Yang M, Kirley TL (2008) Engineered human soluble calcium-activated nucleotidase inhibits coagulation in vitro and thrombosis in vivo. Thromb Res 122(4):541–548

    Article  PubMed  CAS  Google Scholar 

  102. Hart ML, Kohler D, Eckle T, Kloor D, Stahl GL, Eltzschig HK (2008) Direct treatment of mouse or human blood with soluble 5′-nucleotidase inhibits platelet aggregation. Arterioscler Thromb Vasc Biol 28(8):1477–1483

    Article  PubMed  CAS  Google Scholar 

  103. Fuster V, Badimon L, Badimon JJ, Chesebro JH (1992) The pathogenesis of coronary artery disease and the acute coronary syndromes (2). N Engl J Med 326(5):310–318

    Article  PubMed  CAS  Google Scholar 

  104. Huo Y, Schober A, Forlow SB, Smith DF, Hyman MC, Jung S, Littman DR, Weber C, Ley K (2003) Circulating activated platelets exacerbate atherosclerosis in mice deficient in apolipoprotein E. Nat Med 9(1):61–67

    Article  PubMed  CAS  Google Scholar 

  105. Gawaz M, Langer H, May AE (2005) Platelets in inflammation and atherogenesis. J Clin Invest 115(12):3378–3384

    Article  PubMed  CAS  Google Scholar 

  106. Krotz F, Sohn HY, Klauss V (2008) Antiplatelet drugs in cardiological practice: established strategies and new developments. Vasc Health Risk Manag 4(3):637–645

    PubMed  Google Scholar 

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Acknowledgments

This work was supported by NHLBI grant HL93149 to KR. KR is an Established Investigator with the AHA. We apologize to colleagues for potentially not citing other papers because of space constrains.

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  1. Departments of Medicine and Biochemistry, Whitaker Cardiovascular Institute, and Evans Center for Interdisciplinary Biomedical Research, Boston University School of Medicine, CVI, 700 Albany St., Boston, MA, 02118, USA

    Hillary A. Johnston-Cox & Katya Ravid

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Correspondence to Katya Ravid.

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Johnston-Cox, H.A., Ravid, K. Adenosine and blood platelets. Purinergic Signalling 7, 357–365 (2011). https://doi.org/10.1007/s11302-011-9220-4

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