Thrombosis Research
Volume 129, Issue 2 , Pages 116-126 , February 2012

Platelet dysfunction in vascular pathologies and how can it be treated

  • Nicoleta Alexandru

      Affiliations

    • ‘Petru Poni ‘Institute of Macromolecular Chemistry, Iasi, Romania
    • Institute of Cellular Biology and Pathology- Nicolae Simionescu of the Romanian Academy, Bucharest, Romania
    • ,
  • Doina Popov

      Affiliations

    • Institute of Cellular Biology and Pathology- Nicolae Simionescu of the Romanian Academy, Bucharest, Romania
    • ,
  • Adriana Georgescu

      Affiliations

    • ‘Petru Poni ‘Institute of Macromolecular Chemistry, Iasi, Romania
    • Institute of Cellular Biology and Pathology- Nicolae Simionescu of the Romanian Academy, Bucharest, Romania
    • Corresponding Author InformationCorresponding author at: Department of 'Cellular Physiology and Pharmacology', Institute of Cellular Biology and Pathology “Nicolae Simionescu” of the Romanian Academy, 8, BP Hasdeu Street, PO Box 35–14, 050568-Bucharest, Romania. Tel.: +40 1 319 4518; fax: +40 1 319 4519.

Received 26 July 2011 ,Revised 19 September 2011 ,Accepted 22 September 2011.

References 

  1. Inzitari M, Arnold AM, Patel KV, Mercer LD, Karlamangla A, Ding J, et al. Subclinical vascular disease burden and risk for death and cardiovascular events in older community dwellers. J Gerontol A Biol Sci Med Sci. 2011;66A:986–993
  2. Divisón Garrote JA, Massó Orozco J, Carrión Valero L, López Abril J, Carbayo Herencia JA, Artigao Rodenas LM, et al. Trends in prevalence of risk factors and global cardiovascular risk in general population of albacete, Spain (1992–94 a 2004–06). Rev Esp Salud Publica. 2011;85(3):275–284
  3. Balagopal P, de Ferranti SD, Cook S, Daniels SR, Gidding SS, Hayman LL, et al. Nontraditional risk factors and biomarkers for cardiovascular disease: mechanistic, research, and clinical considerations for youth: a scientific statement from the american heart association. Circulation. 2011;123:2749–2769
  4. Shi G, Morrell CN. Platelets as initiators and mediators of inflammation at the vessel wall. Thromb Res. 2011;127(5):387–390
  5. Ripoche J. Blood platelets and inflammation: their relationship with liver and digestive diseases. Clin Res Hepatol Gastroenterol. 2011;35(5):353–357
  6. Antoniades C, Bakogiannis C, Tousoulis D, Demosthenous M, Marinou K, Stefanadis C. Platelet activation in atherogenesis associated with low-grade inflammation. Inflamm Allergy Drug Targets. 2010;9(5):334–345
  7. Boilard E, Nigrovic PA, Larabee K, Watts GFM, Coblyn JS, Weinblatt ME, et al. Platelets amplify inflammation in arthritis via collagen-dependent microparticle production. Science. 2010;327:580–583
  8. Senzel L, Gnatenko DV, Bahou WF. The platelet proteome. Curr Opin Hematol. 2009;16:329–333
  9. Denis MM, Tolley ND, Bunting M, Schwertz H, Jiang H, Lindemann S, et al. Escaping the nuclear confines: signal-dependent pre-mRNA splicing in anucleate platelets. Cell. 2005;122:379–391
  10. Gnatenko DV, Dunn JJ, McCorkle SR, Weissmann D, Perrotta PL, Bahou WF. Transcript profiling of human platelets using microarray and serial analysis of gene expression. Blood. 2003;101:2285–2293
  11. Bugert P, Dugrillon A, Gunaydin A, Eichler H, Kluter H. Messenger RNA profiling of human platelets by microarray hybridization. Thromb Haemost. 2003;90:738–748
  12. Weyrich AS, Lindemann S, Tolley ND, Kraiss LW, Dixon DA, Mahoney TM, et al. Change in protein phenotype without a nucleus: translational control in platelets. Semin Thromb Hemost. 2004;30:491–498
  13. Nagalla S, Shaw C, Kong X, Kondkar AA, Edelstein LC, Ma L, et al. Platelet microRNA-mRNA coexpression profiles correlate with platelet reactivity. Blood. 2011;117:5189–5197
  14. Nieuwland R, Sturk A. Platelet-derived microparticles. In:  Michelson AD editors. Platelets. San Diego: Academic Press; 2002;p. 255–265
  15. Sadallah S, Eken C, Martin PJ, Schifferli JA. Microparticles (ectosomes) shed by stored human platelets downregulate macrophages and modify the development of dendritic. Cells J Immunol. 2011;186:6543–6552
  16. Freyssinet JM, Toti F. Formation of procoagulant microparticles and properties. Thromb Res. 2010;125(Suppl. 1):S46–S48
  17. Garcia BA, Smalley DM, Cho H, Shabanowitz J, Ley K, Hunt DF. The platelet microparticle proteome. J Proteome Res. 2005;4:1516–1521
  18. Piersma SR, Broxterman HJ, Kapci M, de Haas RR, Hoekman K, Verheul HM, et al. Proteomics of the TRAP-induced platelet releasate. J Proteomics. 2009;72:91–109
  19. Mause SF, Weber C. Microparticles: Protagonists of a novel communication network for intercellular information exchange. Circ Res. 2010;107:1047–1057
  20. Peerschke E, Yin AW, Ghebrehlwet B. Complement activation on platelets: implications for vascular inflammation and thrombosis. Mol Immunol. 2010;47:2170–2175
  21. Nurden AT. Platelets, inflammation and tissue regeneration. Thrombosis and Haemostasis, Supplement. 2011;1:1–21
  22. Yeaman MR. Platelets in defense against bacterial pathogens. Cell Mol Life Sci. 2010;67:525–544
  23. Beaulieu LM, Freedman JE. The role of inflammation in regulating platelet production and function: Toll-like receptors in platelets and megakaryocytes. Thromb Res. 2010;125:205–209
  24. Aslam R, Speck ER, Kim M, Crow AR, Bang KWA, Nestel FP, et al. Platelet toll-like receptor expression modulates lipopolysaccharide-induced thrombocytopenia and tumor necrosis factor-alpha production in vivo. Blood. 2006;107:637–641
  25. Gavrilovskaya IN, Gorbunova EE, Mackow ER. Pathogenic hanta viruses direct the adherence of quiescent platelets to infected endothelial cells. J Virol. 2010;84:4832–4839
  26. Nurden AT, Nurden P, Sanchez M, Andia I, Anitua E. Platelets and wound healing. Front Biosci. 2008;13:3525–3548
  27. Blair P, Flaumenhaft R. Platelet α-granules: Basic biology and clinical correlates. Blood Rev. 2009;23:177–189
  28. Del Conde I, Cruz MA, Zhang H, López JA, Afshar-Kharghan V. Platelet activation leads to activation and propagation of the complement system. J Exp Med. 2005;201:871–879
  29. Gasparyan AY, Stavropoulos-Kalinoglou A, Mikhailidis DP, Douglas KM, Kitas GD. Platelet function in rheumatoid arthritis: arthritic and cardiovascular implications. Rheumatol Int. 2011;31(2):153–164
  30. Gasparyan AY, Stavropoulos-Kalinoglou A, Toms TE, Douglas KM, Kitas GD. Association of mean platelet volume with hypertension in rheumatoid arthritis. Inflamm Allergy Drug Targets. 2010;9:45–50
  31. Senturk T. Platelet Function In Inflammatory diseases: Insights from clinical studies. Inflamm Allergy Drug Targets. 2010;
  32. Creager MA, Lüscher TF, Cosentino F, Beckman JA. Diabetes and vascular disease: pathophysiology, clinical consequences, and medical therapy: Part I. Circulation. 2003;108:1527–1532
  33. Stratmann B, Tschoepe D. Pathobiology and cell interactions of platelets in diabetes. Diab Vasc Dis Res. 2005;2:16–23
  34. Angiolillo DJ, Fernandez-Ortiz A, Bernardo E, Ramírez C, Sabaté M, Jimenez-Quevedo P, et al. Platelet function profiles in patients with type 2 diabetes and coronary artery disease on combined aspirin and clopidogrel treatment. Diabetes. 2005;54:2430–2435
  35. Ferroni P, Basili S, Falco A, Davì G. Platelet activation in type 2 diabetes mellitus. J Thromb Haemost. 2004;2:1282–1291
  36. Haramaki N, Ikeda H, Takenaka K, Katoh A, Sugano R, Yamagishi S, et al. Fluvastatin alters platelet aggregability in patients with hypercholesterolemia: possible improvement of intraplatelet redox imbalance via HMG-CoA reductase. Arterioscler Thromb Vasc Biol. 2007;27:1471–1477
  37. Gkaliagkousi E, Corrigall V, Becker S, Winter P, Shah A, Zamboulis C, et al. Decreased platelet nitric oxide contributes to increased circulating monocyte-platelet aggregates in hypertension. European Heart Journal. 2009;30:3048–3054
  38. Virmani R, Burke AP, Farb A, Kolodgie FD. Pathology of the vulnerable plaque. J Am Coll Cardiol. 2006;47:C13–C18
  39. Massberg S, Brand K, Gruner S, Page S, Muller E, Muller I, et al. A critical role of platelet adhesion in the initiation of atherosclerotic lesion formation. J Exp Med. 2002;196:887–896
  40. Seizer P, Gawaz M, May AE. Platelet–monocyte interactions—a dangerous liaison linking thrombosis, inflammation and atherosclerosis. Curr Med Chem. 2008;15:1976–1980
  41. Vasina E, Heemskerk JWM, Weber C, Koenen RR. Platelets and platelet-derived microparticles in vascular inflammatory disease. Inflammation & Allergy - Drug Targets. 2010;9:346–354
  42. Antoniades C, Bakogiannis C, Tousoulis D, Antonopoulos AS, Stefanadis C. The CD40/CD40 ligand system: linking inflammation with atherothrombosis. J Am Coll Cardiol. 2009;54:669–677
  43. Hristov M, Weber C. Progenitor cell trafficking in the vascular wall. J Thromb Haemost. 2009;7(Suppl. 1):31–34
  44. Langer H, May AE, Daub K, Heinzmann U, Lang P, Schumm M, et al. Adherent platelets recruit and induce differentiation of murine embryonic endothelial progenitor cells to mature endothelial cells in vitro. Circ Res. 2006;98:e2–e10
  45. Seizer P, Schiemann S, Merz T, Daub K, Bigalke B, Stellos K, et al. CD36 and macrophage scavenger receptor a modulate foam cell formation via inhibition of lipid-laden platelet phagocytosis. Semin Thromb Hemost. 2010;36:157–162
  46. Gawaz M. Platelets in the onset of atherosclerosis. Blood Cells Mol Dis. 2006;36:206–210
  47. Gawaz M, Stellos K, Langer HF. Platelets modulate atherogenesis and progression of atherosclerotic plaques via interaction with progenitor and dendritic cells. J Thromb Haemost. 2008;6:235–242
  48. Afek A, Kogan E, Maysel-Auslender S, Mor A, Regev E, Rubinstein A, et al. Clopidogrel attenuates atheroma formation and induces a stable plaque phenotype in apolipoprotein E knockout mice. Microvasc Res. 2009;77:364–369
  49. Nofer JR, Brodde MF, Kehrel BE. High density lipoproteins (HDL), platelets and the pathogenesis of atherosclerosis. Clin Exp Pharmacol Physiol. 2010;37:726–735
  50. Eisenhardt SU, Habersberger J, Peter K. Monomeric C-reactive protein generation on activated platelets: the missing link between inflammation and atherothrombotic risk. Trends Cardiovasc Med. 2009;19:232–237
  51. Kucharska-Newton AM, Monda KL, Campbell S, Bradshaw PT, Wagenknecht LE, Boerwinkle E, et al. Association of the platelet GPIIb/IIIa polymorphism with atherosclerotic plaque morphology The Atherosclerosis Risk in Communities (ARIC) Study. Atherosclerosis. 2011;216(1):151–156
  52. Rao GH. Management of type-2 diabetes with anti-platelet therapies: special reference to aspirin. Front Biosci (Schol Ed). 2011;3:1–15
  53. Ferreiro JL, Gómez-Hospital JA, Angiolillo DJ. Platelet abnormalities in diabetes mellitus. Diab Vasc Dis Res. 2010;7:251–259
  54. Gresele P, Guglielmini G, De Angelis M, Ciferri S, Ciofetta M, Falcinelli E, et al. Acute, short-term hyperglycemia enhances shear stress-induced platelet activation in patients with type II diabetes mellitus. J Am Coll Cardiol. 2003;41:1013–1020
  55. Assert R, Scherk G, Bumbure A, Pirags V, Schatz H, Pfeiffer AF. Regulation of protein kinase C by short term hyperglycaemia in human platelets in vivo and in vitro. Diabetologia. 2001;44:188–195
  56. Davì G, Catalano I, Averna M, Notarbartolo A, Strano A, Ciabattoni G, et al. Thromboxane biosynthesis and platelet function in type II diabetes mellitus. N Engl J Med. 1990;322:1769–1774
  57. Kobzar G, Mardla V, Samel N. Short-term exposure of platelets to glucose impairs inhibition of platelet aggregation by cyclooxygenase inhibitors. Platelets. 2011;
  58. Rosado JA. Textbook of hemostasis and blood coagulation. Kerala: Research Signpost; 2009;
  59. Lopez JJ, Camello-Almaraz C, Pariente JA, Salido GM, Rosado JA. Ca2+ accumulation into acidic organelles mediated by Ca2+− and vacuolar H+−ATPases in human platelets. Biochem J. 2005;390(Pt 1):243–252
  60. Zbidi H, Jardin I, Bartegi A, Salido GM, Rosado JA. Ca(2+) leakage rate from agonist-sensitive intracellular pools is altered in platelets from patients with type 2 diabetes. Platelets. 2011;22(4):284–293
  61. Rosado JA, Saavedra FR, Redondo PC, Hernandez-Cruz JM, Salido GM, Pariente JA, et al. Reduced plasma membrane Ca2+−ATPase function in platelets from patients with non-insulin-dependent diabetes mellitus. Haematologica. 2004;89:1142–1144
  62. Alexandru N, Jardín I, Popov D, Simionescu M, García-Estañ J, Salido GM, et al. Effect of homocysteine on calcium mobilisation and platelet function in type 2 diabetes mellitus. J Cell Mol Med. 2008;12(5B):2015–2026
  63. Alexandru N, Popov D, Sbarcea A, Amuzescu M. Platelet free cytosolic calcium concentration during ageing of type 2 diabetic patients. Platelets. 2007;18(7):473–480
  64. Jardı´n I, Redondo PC, Salido GM, Pariente JA, Rosado JA. Endogenously generated reactive oxygen species reduce PMCA activity in platelets from patients with non-insulin-dependent diabetes mellitus. Platelets. 2006;17(5):283–288
  65. Saavedra FR, Redondo PC, Hernandez- Cruz JM, Salido GM, Pariente JA, Rosado JA. Store-operated Ca2+ entry and tyrosine kinase pp 60src hyperactivity are modulated by hyperglycemia in platelets from patients with non insulindependent diabetes mellitus. Arch Biochem Biophys. 2004;432:261–268
  66. El Haouari M, Rosado JA. Platelet signalling abnormalities in patients with type 2 diabetes mellitus: a review. Blood Cells Mol Dis. 2008;41(1):119–123
  67. Redondo PC, Jardín I, Hernandez-Cruz JM, Pariente JA, Salido GM, Rosado JA. Hydrogen peroxide and peroxynitrite enhance Ca2+ mobilization and aggregation in platelets from type 2 diabetic patients. Biochem Biophys Res Commun. 2005;333:794–802
  68. Marzocchi B, Perrone S, Paffetti P, Magi B, Luca B, Tani C, et al. Nonprotein-bound iron and plasma protein oxidative stress at birth. Pediatr Res. 2005;58:1295–1299
  69. Alexandru N, Constantin A, Popov D. Carbonylation of platelet proteins occurs as consequence of oxidative stress and thrombin activation, and is stimulated by ageing and type 2 diabetes. Clin Chem Lab Med. 2008;46(4):528–536
  70. Goswami K, Koner BC. Level of sialic acid residues in platelet proteins in diabetes, aging, and Hodgkin's lymphoma: a potential role of free radicals in desialylation. Biochem Biophys Res Commun. 2002;297:502–505
  71. Olas B, Nowak P, Ponczek M, Wachowicz B. Resveratrol, a natural phenolic compound may reduce carbonylation proteins induced by peroxynitrite in blood platelets. Gen Physiol Biophys. 2006;25:215–222
  72. Olas B, Saluk-Juszczak J, Pawlaczyk I, Nowak P, Kolodziejczyk J, Gancarz R, et al. Antioxidant and antiaggregatory effects of an extract from Conyza canadensis on blood platelets in vitro. Platelets. 2006;17:354–360
  73. Signorello MG, Viviani GL, Armani U, Cerone R, Minniti G, Piana A, et al. Homocysteine, reactive oxygen species and nitric oxide in type 2 diabetes mellitus. Thromb Res. 2007;120:607–613
  74. Koubaa N, Nakbi A, Smaoui M, Abid N, Chaaba R, Abid M, et al. Hyperhomocysteinemia and elevated ox-LDL in Tunisian type 2 diabetic patients: Role of genetic and dietary factors. Clin Biochem. 2007;40:1007–1014
  75. Coppola A, Davi G, De Stefano V, Mancini FP, Cerbone AM, Di Minno G. Homocysteine, coagulation, platelet function, and thrombosis. Semin Thromb Hemost. 2000;26:243–254
  76. Leoncini G, Bruzzese D, Signorello MG. A role for PLCgamma2 in platelet activation by homocysteine. J Cell Biochem. 2007;100:1255–1265
  77. Ho PI, Collins SC, Dhitavat S, Ortiz D, Ashline D, Rogers E, et al. Homocysteine potentiates beta-amyloid neurotoxicity: role of oxidative stress. J Neurochem. 2001;78:249–253
  78. Redondo PC, Salido GM, Rosado JA, Pariente JA. Effect of hydrogen peroxide on Ca2+ mobilisation in human platelets through sulphydryl oxidation dependent and independent mechanisms. Biochem Pharmacol. 2004;67:491–502
  79. Leoncini G, Pascale R, Signorello MG. Effects of homocysteine on L-arginine transport and nitric oxide formation in human platelets. Eur J Clin Invest. 2003;33:713–719
  80. Leoncini G, Bruzzese D, Signorello MG. Activation of p38 MAPKinase/cPLA2 pathway in homocysteine-treated platelets. J Thromb Haemost. 2006;4:209–216
  81. Calzada C, Coulon L, Halimi D, Le Coquil E, Pruneta-Deloche V, Moulin P, et al. In Vitro Glycoxidized low-density lipoproteins and low-density lipoproteins isolated from Type 2 diabetic patients activate platelets via p38 mitogen-activated protein kinase. J Clin Endocrinol Metab. 2007;92:1961–1964
  82. Jindal S, Gupta S, Gupta R, Kakkar A, Singh HV, Gupta K, et al. Platelet indices in diabetes mellitus: indicators of diabetic microvascular complications. Hematology. 2011;16(2):86–89
  83. Gasparyan AY, Ayvazyan L, Mikhailidis DP, Kitas GD. Mean platelet volume: a link between thrombosis and inflammation?. Curr Pharm Des. 2011;17(1):47–58
  84. Shiraishi M, Tani E, Miyamoto A. Modulation of rabbit platelet aggregation and calcium mobilization by platelet cholesterol content. J Vet Med Sci. 2010;72(3):285–292
  85. Gomes AL, Carvalho T, Serpa J, Torre C, Dias S. Hypercholesterolemia promotes bone marrow cell mobilization by perturbing the SDF 1:CXCR4 axis. Blood. 2010;115:3886–3894
  86. Korporaal SJA, Meurs I, Hauer AD, Hildebrand RB, Hoekstra M, Ten Cate H, et al. Deletion of the high-density lipoprotein receptor scavenger receptor BI in mice modulates thrombosis susceptibility and indirectly affects platelet function by elevation of plasma free cholesterol. Arterioscler Thromb Vasc Biol. 2011;31:34–42
  87. Ma Y, Ashraf MZ, Podrez EA. Scavenger receptor BI modulates platelet reactivity and thrombosis in dyslipidemia. Blood. 2010;116:1932–1941
  88. Zimman A, Podrez EA. Regulation of platelet function by Class B Scavenger receptors in hyperlipidemia. ATVB. 2010;30:2350
  89. Nagy B, Jin J, Ashby B, Reilly MP, Kunapuli SP. Contribution of the P2Y12 receptor-mediated pathway to platelet hyperreactivity in hypercholesterolemia. J Thromb Haemost. 2011;9(4):810–819
  90. Li D, Wang Y, Wang K, Zhang L, Chai W, Sun Y, et al. Platelet ADP receptor P2Y12 stabilizes atherosclerosis plaques by regulating alpha granule release and inflammatory cell recruitment blood. ASH Annual Meeting Abstracts. 2010;116:652
  91. Zhao XM, Qin SC. Oxidative stress of platelet and atherosclerosis. Sheng Li Ke Xue Jin Zhan. 2011;42(1):33–38
  92. Stokes KY, Calahan L, Hamric CM, Russell JM, Granger DN. CD40/CD40L contributes to hypercholesterolemia-induced microvascular inflammation. Am J Physiol Heart Circ Physiol. 2009;296:H689–H697
  93. Lievens D, Zernecke A, Seijkens T, Soehnlein O, Beckers L, Munnix ICA, et al. Platelet CD40L mediates thrombotic and inflammatory processes in atherosclerosis. Blood. 2010;116:4317–4327
  94. Huo Y, Schober A, Forlow SB, Smith DF, Hyman MC, Jung S, et al. Circulating activated platelets exacerbate atherosclerosis in mice deficient in apolipoprotein E. Nat Med. 2003;9:61–67
  95. Daub K, Seizer P, Stellos K, Kramer BF, Bigalke B, Schaller M, et al. Oxidized LDL-activated platelets induce vascular inflammation. Semin Thromb Hemost. 2010;36(2):146–156
  96. Stokes KY, Russell JM, Jennings MH, Alexander JS, Granger DN. Platelet-associated NAD(P)H oxidase contributes to the thrombogenic phenotype induced by hypercholesterolemia. Free Radic Biol Med. 2007;43:22–30
  97. Varol E, Ali Uysal B, Ozaydin M. Platelet indices in patients with pulmonary arterial hypertension. Clin Appl Thromb/Hemost. 2011;
  98. Ulrich S, Huber LC, Fischler M, Treder U, Maggiorini M, Eberli FR, et al. Platelet serotonin content and transpulmonary platelet serotonin gradient in patients with pulmonary hypertension. Respiration. 2011;81(3):211–216
  99. Diehl P, Aleker M, Helbing T, Sossong V, Germann M, Sorichter S, et al. Increased platelet, leukocyte and endothelial microparticles predict enhanced coagulation and vascular inflammation in pulmonary hypertension. J Thromb Thrombolysis. 2011;31(2):173–179
  100. Maeda NY, Carvalho JH, Otake AH, Mesquita SM, Bydlowski SP, Lopes AA. Platelet protease-activated receptor 1 and membrane expression of P-selectin in pulmonary arterial hypertension. Thromb Res. 2010;125(1):38–43
  101. Kaya MG, Yarlioglues M, Gunebakmaz O, Gunturk E, Inanc T, Dogan A, et al. Platelet activation and inflammatory response in patients with non-dipper hypertension. Atherosclerosis. 2010;209:278–282
  102. Minuz P, Patrignani P, Gaino S, Seta F, Capone ML, Tacconelli S, et al. Determinants of platelet activation in human essential hypertension. Hypertension. 2004;43:64–70
  103. Germanò G, Sanguigni V, Pignatelli P, Caccese D, Lenti L, Ragazzo M, et al. Enhanced platelet release of superoxide anion in systemic hypertension: role of AT1 receptors. J Hypertens. 2004;22:1151–1156
  104. Alexandru N, Popov D, Dragan E, Andrei E, Georgescu A. Platelet activation in hypertension associated with hypercholesterolemia; effects of irbesartan. J Thromb Hemost. 2011;9(1):173–184
  105. Iyu D, Atucha NM, Martinez-Prieto C, Ortiz MC, Garcia-Estan J. Altered calcium signaling in platelets from nitric oxide-deficient hypertensive rats. Cell Commun Signal. 2004;2:1
  106. Li Y, Adachi T, Bolotina VM, Knowles C, Ault KA, Cohen RA. Abnormal platelet function and calcium handling in Dahl salt-hypertensive rats. Hypertension. 2001;37(4):1129–1135
  107. Gkaliagkousi E, Ritter J, Ferro A. Platelet-Derived Nitric Oxide Signaling and Regulation. Circ Res. 2007;101:654–662
  108. El Haouari M, Rosado JA. Platelet function in hypertension. Blood Cells Mol Dis. 2009;42(1):38–43
  109. Gkaliagkousi E, Douma S, Zamboulis C, Ferro A. Nitric oxide dysfunction in vascular endothelium and platelets: role in essential hypertension. J Hypertens. 2009;27:2310–2320
  110. Moss MB, Siqueira MA, Mann GE, Brunini TM, Mendes-Ribeiro AC. Platelet aggregation in arterial hypertension: is there a nitric oxide-urea connection?. Clin Exp Pharmacol Physiol. 2010;37(2):167–172
  111. Kumar A, Cannon CP. Acute coronary syndromes: diagnosis and management, part II. Mayo Clin Proc. 2009;84:1021–1036
  112. Di Minno MN, Guida A, Camera M, Colli S, Minno GD, Tremoli E. Overcoming limitations of current antiplatelet drugs: A concerted effort for more profitable strategies of intervention. Ann Med. 2011;43(7):531–544
  113. Maree AO, Fitzgerald DJ. Variable Platelet Response to Aspirin and Clopidogrel in Atherothrombotic disease. Circulation. 2007;115:2196–2207
  114. Li N, Hu H, Hjemdahl P. Aspirin treatment does not attenuate platelet or leukocyte activation as monitored by whole blood flow cytometry. Thromb Res. 2003;111:165–170
  115. Klinkhardt U, Bauersachs R, Adams J, Graff J, Lindhoff-Last E, Harder S. Clopidogrel but not aspirin reduces P-selectin expression and formation of platelet-leukocyte aggregates in patients with atherosclerotic vascular disease. Clin Pharmacol Ther. 2003;73(3):232–241
  116. Moshfegh K, Redondo M, Julmy F, Wuillemin WA, Gebauer MU, Haeberli A, et al. Antiplatelet effects of clopidogrel compared with aspirin after myocardial infarction: enhanced inhibitory effects of combination therapy. J Am Coll Cardiol. 2000;36(3):699–705
  117. Di Minno G, Violi F. Aspirin resistance and diabetic angiopathy: back to the future. Thrombosis Research. 2004;113:97–99
  118. Rocca B, Secchiero P, Ciabattoni G, Ranelletti FO, Catani L, Guidotti L, et al. Cyclooxygenase-2 expression is induced during human megakaryopoiesis and characterizes newly formed platelets. Proc Natl Acad Sci USA. 2002;99:7634–7639
  119. Eikelboom JW, Hirsh J, Weitz JI, Johnston M, Yi Q, Yusuf S. Aspirin-resistant thromboxane biosynthesis and the risk of myocardial infarction, stroke, or cardiovascular death in patients at high risk for cardiovascular events. Circulation. 2002;105:1650–1655
  120. Watala C, Golanski J, Pluta J, Boncler M, Rozalski M, Wieclawska B, et al. Reduced sensitivity of platelets from type 2 diabetic patients to acetylsalicylic acid (aspirin) its relation to metabolic control. Thromb Res. 2004;113:101–113
  121. Cambria-Kiely JA, Gandhi PJ. Aspirin resistance and genetic polymorphisms. J Thromb Thrombolysis. 2002;14:51–58
  122. Halushka MK, Walker LP, Halushka PV. Genetic variation in cyclooxygenase 1: effects on response to aspirin. Clin Pharmacol Ther. 2003;73:122–130
  123. Levine GN, Berger PB, Cohen DJ, Maree AO, Rosenfield K, Wiggins BS, et al. Newer pharmacotherapy in patients undergoing percutaneous coronary interventions: a guide for pharmacists and other health care professionals. Pharmacotherapy. 2006;26:1537–1556
  124. Ombrello C, Block RC, Morrell CN. Our expanding view of platelet functions and its clinical implications. J Cardiovasc Trans Res. 2010;3:538–546
  125. Angiolillo DJ, Badimon JJ, Saucedo JF, Frelinger AL, Michelson AD, Jakubowski JA, et al. A pharmacodynamic comparison of prasugrel vs. high-dose clopidogrel in patients with type 2 diabetes mellitus and coronary artery disease: results of the Optimizing anti-Platelet Therapy In diabetes MellitUS (OPTIMUS)-3 Trial. Eur Heart J. 2011;32:838–846
  126. Braun OO, Johnell M, Varenhorst C, James S, Brandt JT, Jakubowski JA, et al. Greater reduction of platelet activation markers and platelet-monocyte aggregates by prasugrel compared to clopidogrel in stable coronary artery disease. Thromb Haemost. 2008;100:626–633
  127. Antonino MJ, Mahla E, Bliden KP, Tantry US, Gurbel PA. Effect of long-term clopidogrel treatment on platelet function and inflammation in patients undergoing coronary arterial stenting. Am J Cardiol. 2009;103(11):1546–1550
  128. Van Giezen JJJ, Humphries RG. Preclinical and clinical studies with selective reversible direct P2Y12 antagonists. Sem Thromb Hemost. 2005;31:195–204
  129. Cattaneo M, Podda GM. State of the art of new P2Y12 antagonists. Intern Emerg Med. 2010;5:385–391
  130. Passacquale G, Ferro A. Current concepts of platelet activation: possibilities for therapeutic modulation of heterotypic versus homotypic aggregation. Br J Clin Pharmacol. 2011;
  131. Bosch X, Marrugat J, Sanchis J. Platelet glycoprotein IIb/IIIa blockers during percutaneous coronary intervention and as the initial medical treatment of non-ST segment elevation acute coronary syndromes. Cochrane Database Syst Rev. 2010;8(9):CD002130
  132. Goto S, Yamaguchi T, Ikeda Y, Kato K, Yamaguchi H, Jensen P. Safety and exploratory efficacy of the novel thrombin receptor (par-1) antagonist sch530348 for non-st-segment elevation acute coronary syndrome. J Atheroscler Thromb. 2010;17(2):156–164
  133. Serebruany VL, Kogushi M, Dastros-Pitei D, Flather M, Bhatt DL. Bhatt, The in-vitro effects of e5555, a proteaseactivated receptor (par)-1 antagonist, on platelet biomarkers in healthy volunteers and patients with coronary artery disease. Thromb Haemost. 2009;102(1):111–119
  134. Schondorf T, Musholt PB, Hohberg C, Forst T, Lehmann U, Fuchs W, et al. The fixed combination of pioglitazone and metformin improves biomarkers of platelet function and chronic inflammation in Type 2 diabetes patients: results from the PIOfix study. J Diabetes Sci Technol. 2011;5(2):426–432
  135. Sadowitz B, Maier KG, Gahtan V. Basic Science Review: Statin therapy-part I: the pleiotropic effects of statins in cardiovascular disease vascular. Endovascular Surgery. 2010;44:241–251
  136. Panes O, Acevedo M, Matus V, Sáez CG, Pereira J, Mezzano D. Platelet tissue factor activity in patients with hypercholesterolemia: modulation of procoagulant activity by statins. Blood (ASH Annual Meeting Abstracts). 2010;116–156
  137. Calkin AC, Drew BG, Ono A, Duffy SJ, Gordon MV, Schoenwaelder SM, et al. Reconstituted high-density lipoprotein attenuates platelet function in individuals with Type 2 diabetes mellitus by promoting cholesterol efflux. Circulation. 2009;120:2095–2104
  138. Keefe AD, Shaub RG. Aptamers as candidate therapeutics for cardiovascular indications. Curr Opin Pharm. 2008;8:147–152
  139. Diener JL, Daniel Lagassé HA, Duerschmied D, Merhi Y, Tanguay JF, Hutabarat R, et al. Hutabarat et al, Inhibition of von Willebrand factor-mediated platelet activation and thrombosis by the anti-von Willebrand factor A1-domain aptamer ARC1779. J Thromb Haemost. 2009;7(7):1155–1162
  140. Gilbert JC, DeFeo-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;116:2678–2686
  141. Chae JR, Cho YL, Park JY, Lee JD, Kang WJ. Visualization of tenascin-C activity in atherosclerosis using fluorescence labeled aptamer. Presentation Number 1087B. September 11, 2010;15:15–16:45 / Room: Exhibit Hall
  142. Maiese K, Chong ZZ, Shang YC, Hou J. Novel avenues of drug discovery and biomarkers for diabetes mellitus. J Clin Pharmacol. 2011;51:128–152
  143. Pignatelli P, Carnevale R, Cangemi R, Loffredo L, Sanguigni V, Stefanutti C, et al. Atorvastatin inhibits gp91phox circulating levels in patients with hypercholesterolemia. Arterioscler Thromb Vasc Biol. 2010;30:360–367
  144. Puccetti L, Santilli F, Pasqui AL, Lattanzio S, Liani R, Ciani F, et al. Effects of atorvastatin and rosuvastatin on thromboxane-dependentplatelet activation and oxidative stress in hypercholesterolemia. Atherosclerosis. 2011;214(1):122–128
  145. Marwali MR, Hu CP, Mohandas B, Dandapat A, Deonikar P, Chen J, et al. Modulation of ADP-induced platelet activation by aspirin and pravastatin: Role of lectin-like oxidized low-density lipoprotein receptor-1, nitric oxide, oxidative stress, and inside-out integrin signaling. JPET. 2007;322:1324–1332
  146. Natella F, Nardini M, Virgili F, Scaccini C. Role of dietary polyphenols in the platelet aggregation network – a review of the in vitro studies. Curr Top Nutraceut Res. 2006;4:1–22
  147. Guerrero JA, Navarro-Nun˜ ez L, Lozano ML, Martínez C, Vicente V, Gibbins JM, et al. Flavonoids inhibit the platelet TxA2 signalling pathway and antagonize TxA2 receptors (TP) in platelets and smooth muscle cells. Br J Clin Pharmacol. 2007;64:133–144
  148. Nardini M, Natella F, Scaccini C. Role of dietary polyphenols in platelet aggregation. A review of the supplementation studies. Platelets. 2007;18:224–243
  149. Pignatelli P, Di Santo S, Buchetti B, Sanguigni V, Brunelli A, Violi F. Polyphenols enhance platelet nitric oxide by inhibiting protein kinase C-dependent NADPH oxidase activation: effect on platelet recruitment. FASEB J. 2006;20:1082–1089
  150. Violi F, Pignatelli P, Basili S. Nutrition, Supplements, and Vitamins in Platelet Function and Bleeding. Circulation. 2010;121:1033–1044
  151. Vitseva O, Varghese S, Chakrabarti S, Folts JD, Freedman JE. Grape seed and skin extracts inhibit platelet function and release of reactive oxygen intermediates. J Cardiovasc Pharmacol. 2005;46:445–451
  152. El Haouari M, Rosado JA. Modulation of platelet function and signaling by flavonoids. Mini Rev Med Chem. 2011;11:131–142
  153. Ostertag LM, O'Kennedy N, Kroon PA, Duthie GG, de Roos B. Impact of dietary polyphenols on human platelet function – A critical review of controlled dietary intervention studies. Mol Nutr Food Res. 2010;54:60–81
  154. Pearson DA, Paglieroni TG, Rein D, Wun T, Schramm DD, Wang JF, et al. The effects of flavanol-rich cocoa and aspirin on ex vivo platelet function. Thromb Res. 2002;106:191–197
  155. Verstuyft C, Simon T, Kim RB. Personalized medicine and antiplatelet therapy: ready for prime time?. Eur Heart J. 2009;30:1943–1963

PII: S0049-3848(11)00513-5

doi: 10.1016/j.thromres.2011.09.026

Thrombosis Research
Volume 129, Issue 2 , Pages 116-126 , February 2012

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