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Platelet Biology and Receptor Pathways

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Abstract

The main function of platelets is to participate in primary hemostasis through four distinct steps: adhesion, activation, secretion, and aggregation. Unraveling the molecular mechanisms underlying these steps has led to a better understanding of the pathophysiology of bleeding disorders, on one hand, and of thrombotic diseases, such as acute coronary syndromes, on the other. Platelets are cytoplasmic fragments of megakaryocytes formed in the bone marrow. They lack nuclei but contain organelles and structures, such as mitochondria, microtubules, and granules. Platelet granules contain different bioactive chemical mediators, many of which have a fundamental role in hemostasis and/or tissue healing. The platelet cytoplasm contains an open canalicular system that increases the effective surface area for the intake of stimulatory agonists and the release of effector substances. The submembrane region contains microfilaments of actin and myosin that mediate morphologic alterations characteristic of shape change. Resting platelets remain in the circulation for an average of approximately 10 days before being removed by macrophages of the reticuloendothelial system. A wide variety of transmembrane receptors cover the platelet membrane, including many integrins, leucine-rich repeat receptors, G protein-coupled receptors, proteins belonging to the immunoglobulin superfamily, C-type lectin receptors, tyrosine kinase receptors, and a variety of other types. In this article, we will review platelet biology under physiological and pathological conditions, with particular emphasis on the function of their membrane receptors.

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References

  1. Jurk, K., & Kehrel, B. E. (2005). Platelets: Physiology and biochemistry. Seminars in Thrombosis and Hemostasis, 31(4), 381–392.

    Article  PubMed  CAS  Google Scholar 

  2. Schulze, H., & Shivdasani, R. A. (2005). Mechanisms of thrombopoiesis. Journal of Thrombosis and Haemostasis, 3(8), 1717–1724.

    Article  PubMed  CAS  Google Scholar 

  3. Rendu, F., & Brohard-Bohn, B. (2001). The platelet release reaction: Granules’ constituents, secretion and functions. Platelets, 12, 261–273.

    Article  PubMed  CAS  Google Scholar 

  4. Escolar, G., & White, J. G. (1991). The platelet open canalicular system: A final common pathway. Blood Cells, 17, 467–485.

    PubMed  CAS  Google Scholar 

  5. Fox, J. E. (1993). The platelet cytoskeleton. Thrombosis and Haemostasis, 70, 884–893.

    PubMed  CAS  Google Scholar 

  6. McNicol, A., & Israels, S. J. (1999). Platelet dense granules: Structure, function and implications for haemostasis. Thrombosis Research, 95, 1–18.

    Article  PubMed  CAS  Google Scholar 

  7. Heijnen, H. F., Debili, N., Vainchencker, W., Breton-Gorius, J., Geuze, H. J., & Sixma, J. J. (1998). Multivesicular bodies are an intermediate stage in the formation of platelet alpha-granules. Blood, 91(7), 2313–2325.

    PubMed  CAS  Google Scholar 

  8. Harrison, P., & Cramer, E. M. (1993). Platelet alpha-granules. Blood Reviews, 7, 52–62.

    Article  PubMed  CAS  Google Scholar 

  9. Semple, J. W., Italiano, J. E., Jr., & Freedman, J. (2011). Platelets and the immune continuum. Nature Reviews Immunology, 11(4), 264–274.

    Article  PubMed  CAS  Google Scholar 

  10. Angiolillo, D. J., Ueno, M., & Goto, S. (2010). Basic principles of platelet biology and clinical implications. Circulation Journal, 74, 597–607.

    Article  PubMed  CAS  Google Scholar 

  11. Varga-Szabo, D., Pleines, I., & Nieswandt, B. (2008). Cell adhesion mechanisms in platelets. Arteriosclerosis, Thrombosis, and Vascular Biology, 28, 403–412.

    Article  PubMed  CAS  Google Scholar 

  12. Kroll, M. H., Hellums, J. D., McIntire, L. V., Schafer, A. I., & Moake, J. L. (1996). Platelets and shear stress. Blood, 88, 1525–1541.

    PubMed  CAS  Google Scholar 

  13. Ballerman, B. J., Dardik, A., Eng, E., & Liu, A. (1998). Shear stress and the endothelium. Kidney International. Supplement, 67, S100–S108.

    Article  Google Scholar 

  14. Ikeda, Y., Handa, M., Kawano, K., Kamata, T., Murata, M., Araki, Y., et al. (1991). The role of von Willebrand factor and fibrinogen in platelet aggregation under varying shear stress. The Journal of Clinical Investigation, 87(4), 1234–1240.

    Article  PubMed  CAS  Google Scholar 

  15. Lisman, T., Raynal, N., Groeneveld, D., Maddox, B., Peachey, A. R., Huizinga, E. G., et al. (2006). A single high-affinity binding site for von Willebrand Factor in collagen III, identified using synthetic triple-helical peptides. Blood, 108, 3753–3756.

    Article  PubMed  CAS  Google Scholar 

  16. Kumar, R. A., Dong, J. F., Thaggard, J. A., Cruz, M. A., Lopez, J. A., & McIntire, L. V. (2003). Kinetics of GPIb alpha-vWF-A1 tether bond under flow: Effect of GPIb alpha mutations on the association and dissociation rates. Biophysical Journal, 85, 4099–4109.

    Article  PubMed  CAS  Google Scholar 

  17. Savage, B., Almus-Jacobs, F., & Ruggeri, Z. M. (1998). Specific synergy of multiple substrate–receptor interactions in platelet thrombus formation under flow. Cell, 94, 657–666.

    Article  PubMed  CAS  Google Scholar 

  18. Van de Walle, G. R., Vanhoorelbeke, K., Majer, Z., Illyes, E., Baert, J., Pareyn, I., et al. (2005). Two functional active conformations of the integrin alpha 2 beta 1, depending on activation condition and cell type. Journal of Biological Chemistry, 280, 36873–36882.

    Article  PubMed  Google Scholar 

  19. Nieswandt, B., & Watson, S. P. (2003). Platelet-collagen interaction: Is GPVI the central receptor? Blood, 102, 449–461.

    Article  PubMed  CAS  Google Scholar 

  20. Dale, G. L., Friese, P., Batar, P., et al. (2002). Stimulated platelets use serotonin to enhance their retention of procoagulant proteins on the cell surface. Nature, 415, 175–179.

    Article  PubMed  CAS  Google Scholar 

  21. Coller, B. S., Scudder, L. E., Beer, J., Gold, H. K., Folts, J. D., Cavagnaro, J., et al. (1991). Monoclonal antibodies to platelet glycoprotein IIb/IIIa as antithrombotic agents. Annals of the New York Academy of Sciences, 614, 193–213.

    Article  PubMed  CAS  Google Scholar 

  22. Madan, M., Berkowitz, S. D., & Tcheng, J. E. (1998). Glycoprotein IIb/IIIa integrin blockade. Circulation, 98, 2629–2635.

    Article  PubMed  CAS  Google Scholar 

  23. Linkoff, A. M., Califf, R. M., & Topol, E. J. (2000). Platelet glycoprotein blockade in coronary artery disease. Journal of the American College of Cardiology, 35, 1103–1115.

    Article  Google Scholar 

  24. Anderson, K. M., Califf, R. M., Stone, G. W., Nemann, F.-J., Montalescot, G., Miller, D. P., et al. (2001). Long-term mortality benefit with abciximab in patients undergoing percutaneous coronary intervention. Journal of the American College of Cardiology, 37, 2059–2065.

    Article  PubMed  CAS  Google Scholar 

  25. Offermanns, S. (2006). Activation of platelet function through G protein coupled receptors. Circulation Research, 99, 1293–1304.

    Article  PubMed  CAS  Google Scholar 

  26. Abbracchio, M. P., Burnstock, G., Boeynaems, J. M., Barnard, E. A., Boyer, J. L., Kennedy, C., et al. (2006). International Union of Pharmacology LVIII: Update on the P2Y G protein-coupled nucleotide receptors: From molecular mechanisms and pathophysiology to therapy. Pharmacological Reviews, 58, 281–341.

    Article  PubMed  CAS  Google Scholar 

  27. Ohlmann, P., Castro, S., Brown, G. G., Jr., Gachet, C., Jacobson, K. A., & Harden, T. K. (2010). Quantification of recombinant and platelet P2Y(1) receptors utilizing a [(125)I]-labeled high-affinity antagonist 2-iodo-N(6)-methyl-(N)-methanocarba-2′-deoxyadenosine-3′,5′-bisphosphate ([(125)I]MRS2500). Pharmacological Research, 62(4), 344–351.

    Article  PubMed  CAS  Google Scholar 

  28. Jin, J., Daniel, J. L., & Kunapuli, S. P. (1998). Molecular basis for ADP-induced platelet activation. II. The P2Y1 receptor mediates ADP-induced intracellular calcium mobilization and shape change in platelets. Journal of Biological Chemistry, 273(4), 2030–2034.

    Article  PubMed  CAS  Google Scholar 

  29. Savi, P., Beauverger, P., Labouret, C., Delfaud, M., Salel, V., Kaghad, M., et al. (1998). Role of P2Y1 purinoceptor in ADP-induced platelet activation. FEBS Letters, 422(3), 291–295.

    Article  PubMed  CAS  Google Scholar 

  30. Mangin, P., Ohlmann, P., Eckly, A., Cazenave, J. P., Lanza, F., & Gachet, C. (2004). The P2Y receptor plays an essential role in the platelet shape change induced by collagen when TxA2 formation is prevented. Journal of Thrombosis and Haemostasis, 2(6), 969–977.

    Article  PubMed  CAS  Google Scholar 

  31. Hardy, A. R., Jones, M. L., Mundell, S. J., & Poole, A. W. (2004). Reciprocal cross-talk between P2Y1 and P2Y12 receptors at the level of calcium signaling in human platelets. Blood, 104(6), 1745–1752.

    Article  PubMed  CAS  Google Scholar 

  32. Yang, J., Wu, J., Jiang, H., Mortensen, R., Austin, S., Manning, D. R., et al. (2002). Signaling through Gi family members in platelets. Redundancy and specificity in the regulation of adenylyl cyclase and other effectors. Journal of Biological Chemistry, 277(48), 46035–46042.

    Article  PubMed  CAS  Google Scholar 

  33. Martin, V., Guillermet-Guibert, J., Chicanne, G., Cabou, C., Jandrot-Perrus, M., Plantavid, M., et al. (2010). Deletion of the p110beta isoform of phosphoinositide 3-kinase in platelets reveals its central role in Akt activation and thrombus formation in vitro and in vivo. Blood, 115(10), 2008–2013.

    Article  PubMed  CAS  Google Scholar 

  34. Hirsch, E., Bosco, O., Tropel, P., Laffargue, M., Calvez, R., Altruda, F., et al. (2001). Resistance to thromboembolism in PI3Kgamma-deficient mice. The FASEB Journal, 15(11), 2019–2021.

    CAS  Google Scholar 

  35. Jin, J., & Kunapuli, S. P. (1998). Coactivation of two different G protein-coupled receptors is essential for ADP-induced platelet aggregation. Proceedings National Academy Science USA, 95(14), 8070–8074.

    Article  CAS  Google Scholar 

  36. Storey, R. F., Judge, H. M., Wilcox, R. G., & Heptinstall, S. (2002). Inhibition of ADP-induced P-selectin expression and platelet-leukocyte conjugate formation by clopidogrel and the P2Y12 receptor antagonist AR-C69931MX but not aspirin. Thrombosis and Haemostasis, 88, 488–494.

    PubMed  CAS  Google Scholar 

  37. FitzGerald, G. A. (1991). Mechanisms of platelet activation: Thromboxane A2 as an amplifying signal for other agonists. The American Journal of Cardiology, 68, 11B–15B.

    Article  PubMed  CAS  Google Scholar 

  38. Coughlin, S. R. (1999). How the protease thrombin talks to cells. Proceedings of the National Academy of Sciences of the United States of America, 96, 11023–7.

    Article  PubMed  CAS  Google Scholar 

  39. Ossovskaya, V. S., & Bunnett, N. W. (2004). Protease-activated receptors: Contribution to physiology and disease. Physiological Reviews, 84, 579–621.

    Article  PubMed  CAS  Google Scholar 

  40. Vu, T. K., Hung, D. T., Wheaton, VI, & Coughlin, S. R. (1991). Molecular cloning of a functional thrombin receptor reveals a novel proteolytic mechanism of receptor activation. Cell, 64, 1057–1068.

    Article  PubMed  CAS  Google Scholar 

  41. O’Brien, P. J., Molino, M., Kahn, M., & Brass, L. F. (2001). Protease activated receptors: Theme and variations. Oncogene, 20, 1570–1581.

    Article  PubMed  Google Scholar 

  42. Kahn, M. L., Nakanishi-Matsui, M., Shapiro, M. J., Ishihara, H., & Coughlin, S. R. (1999). Protease-activated receptors 1 and 4 mediate activation of human platelets by thrombin. The Journal of Clinical Investigation, 103, 879–887.

    Article  PubMed  CAS  Google Scholar 

  43. Steinhoff, M., Buddenkotte, J., Shpacovitch, V., Rattenholl, A., Moormann, C., Vergnolle, N., et al. (2005). Proteinase-activated receptors: Transducers of proteinase-mediated signaling in inflammation and immune response. Endocrine Reviews, 26, 1–43.

    Article  PubMed  CAS  Google Scholar 

  44. Shapiro, M. J., Weiss, E. J., Faruqi, T. R., & Coughlin, S. R. (2000). Protease-activated receptors 1 and 4 are shut off with distinct kinetics after activation by thrombin. Journal of Biological Chemistry, 275, 25216–25221.

    Article  PubMed  CAS  Google Scholar 

  45. Newman, P. J., Gorski, J., & White, G. C., 2nd. (1988). Enzymatic amplification of platelet-specific messenger RNA using the polymerase chain reaction. The Journal of Clinical Investigation, 82, 739–743.

    Article  PubMed  CAS  Google Scholar 

  46. Gnatenko, D. V., Dunn, J. J., & McCorkle, S. R. (2003). Transcript profiling of human platelets using microarray and serial analysis of gene expression. Blood, 101, 2285–2293.

    Article  PubMed  CAS  Google Scholar 

  47. Kieffer, N., Guichard, J., & Farcet, J. P. (1987). Biosynthesis of major platelet proteins in human blood platelets. European Journal of Biochemistry, 164, 189–195.

    Article  PubMed  CAS  Google Scholar 

  48. Weyrich, A. S., Lindemann, S., & Tolley, N. D. (2004). Change in protein phenotype without a nucleus: Translational control in platelets. Seminars in Thrombosis and Hemostasis, 30, 491–498.

    Article  PubMed  CAS  Google Scholar 

  49. Healy, A. M., Pickard, M. D., & Pradhan, A. D. (2006). Platelet expression profiling and clinical validation of myeloid-related protein-14 as a novel determinant of cardiovascular events. Circulation, 113, 2278–2284.

    Article  PubMed  CAS  Google Scholar 

  50. Denis, M. M., Tolley, N. D., & Bunting, M. (2005). Escaping the nuclear confines: Signal-dependent pre-mRNA splicing in anucleate platelets. Cell, 122, 379–391.

    Article  PubMed  CAS  Google Scholar 

  51. Schwertz, H., Tolley, N. D., & Foulks, J. M. (2006). Signal-dependent splicing of tissue factor pre-mRNA modulates the thrombogenicity of human platelets. The Journal of Experimental Medicine, 203, 2433–2440.

    Article  PubMed  CAS  Google Scholar 

  52. Baek, D., Villen, J., & Shin, C. (2008). Nature, 455, 64–71.

    Article  PubMed  CAS  Google Scholar 

  53. Small, E.M., Frost, R.J., Olson, E.N. (2010). MicroRNAs add a new dimension to cardiovascular disease. Circulation, 121, 1022–1032.

    Google Scholar 

  54. Landry, P., Plante, I., & Ouellet, D. L. (2009). Existence of a microRNA pathway in anucleate platelets. Nature Structural and Molecular Biology, 16(9), 961–966.

    Article  PubMed  CAS  Google Scholar 

  55. Cimmino, G., Tarallo, R., Nassa, G., De Filippo, M.R., Conte, S., Pellegrino, G., Morello, A., Cirillo, P., Weisz, A., Golino, P. (2012). Activation modulates miRNA expression profile in platelets: New insights into the pathophysiology of platelet activation. AHA Scientific Session, Abstract 12998

  56. Damman, P., Woudstra, P., Kuijt, W. J., de Winter, R. J., & James, S. K. (2012). P2Y12 platelet inhibition in clinical practice. Journal of Thrombosis and Thrombolysis, 33(2), 143–153.

    Article  PubMed  CAS  Google Scholar 

  57. Chamorro, A. (2009). TP receptor antagonism: A new concept in atherothrombosis and stroke prevention. Cerebrovascular Diseases, 27(Suppl 3), 20–27. Epub 2009 May 14.

    Article  PubMed  CAS  Google Scholar 

  58. Nieswandt, B., Schulte, V., Bergmeier, W., Mokhtari-Nejad, R., Rackebrandt, K., Cazenave, J. P., et al. (2001). Long-term antithrombotic protection by in vivo depletion of platelet glycoprotein VI in mice. The Journal of Experimental Medicine, 193, 459–469.

    Article  PubMed  CAS  Google Scholar 

  59. Li, H., Lockyer, S., Concepcion, A., Gong, X., Takizawa, H., Guertin, M., et al. (2007). The Fab fragment of a novel anti-GPVI monoclonal antibody, OM4, reduces in vivo thrombosis without bleeding risk in rats. Arteriosclerosis, Thrombosis, and Vascular Biology, 27, 1199–1205.

    Article  PubMed  CAS  Google Scholar 

  60. Massberg, S., Konrad, I., Bültmann, A., Schulz, C., Münch, G., Peluso, M., et al. (2004). Soluble glycoprotein VI dimer inhibits platelet adhesion and aggregation to the injured vessel wall in vivo. The FASEB Journal, 18, 397–399.

    CAS  Google Scholar 

  61. Ungerer, M., Rosport, K., Bültmann, A., Piechatzek, R., Uhland, K., Schlieper, P., et al. (2011). Novel antiplatelet drug revacept (dimeric glycoprotein VI-Fc) specifically and efficiently inhibited collagen-induced platelet aggregation without affecting general hemostasis in humans. Circulation, 123, 1891–1899.

    Article  PubMed  CAS  Google Scholar 

  62. Vanhoorelbeke, K., Ulrichts, H., Schoolmeester, A., & Deckmyn, H. (2003). Inhibition of platelet adhesion to collagen as a new target for antithrombotic drugs. Current Drug Targets. Cardiovascular & Haematological Disorders, 3, 125–140.

    Article  CAS  Google Scholar 

  63. Van Bockstaele, F., Holz, J. B., & Revets, H. (2009). The development of nanobodies for therapeutic applications. Current Opinion in Investigational Drugs, 10(11), 1212–1224.

    PubMed  Google Scholar 

  64. ClinicalTrials.gov. (2009). Comparative study of ALX-0081 versus GPIIb/IIIa inhibitor in high risk percutaneous coronary intervention (PCI) patients. Retrieved from http://clinicaltrials.gov/ct2/show/record/NCT01020383.

  65. Tricoci, P., Huang, Z., Held, C., Moliterno, D. J., Armstrong, P. W., Van de Werf, F., et al. (2012). Thrombin-receptor antagonist vorapaxar in acute coronary syndromes. The New England Journal of Medicine, 366(1), 20–33. Epub 2011 Nov 13.

    Article  PubMed  CAS  Google Scholar 

  66. Morrow, D. A., Braunwald, E., Bonaca, M. P., Ameriso, S. F., Dalby, A. J., Fish, M. P., et al. (2012). Vorapaxar in the secondary prevention of atherothrombotic events. The New England Journal of Medicine, 366(15), 1404–1413.

    Article  PubMed  CAS  Google Scholar 

  67. Morrow, D. A., Scirica, B. M., Fox, K. A., Berman, G., Strony, J., Veltri, E., et al. (2009). Evaluation of a novel antiplatelet agent for secondary prevention in patients with a history of atherosclerotic disease: Design and rationale for the Thrombin-Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events (TRA 2 degrees P)-TIMI 50 trial. American Heart Journal, 158(335–341), e333.

    Google Scholar 

  68. Warner, T. D., & Mitchell, J. A. (2004). Cyclooxygenases: New forms, new inhibitors, and lessons from the clinic. The FASEB Journal, 18, 790–804.

    Article  CAS  Google Scholar 

  69. Smith, W. L., & Langenbach, R. (2001). Why there are two cyclooxygenase isozymes. The Journal of Clinical Investigation, 107(12), 1491–1495.

    Article  PubMed  CAS  Google Scholar 

  70. Chandrasekharan, N. V., Dai, H., Roos, L. T., Evanson, N. K., Tomsik, J., Elton, T. S., et al. (2002). COX-3, a cyclooxygenase-1 variant inhibited by acetaminophen and other analgesic/antipyretic drugs: Cloning, structure, and expression. Proceedings of the National Academy of Sciences of the United States of America, 99(21), 13926–13931.

    Article  PubMed  CAS  Google Scholar 

  71. Dubois, R. N., Abramson, S. B., Crofford, L., Gupta, R. A., Simon, L. S., Van De Putte, L. B., et al. (1998). Cyclooxygenase in biology and disease. The FASEB Journal, 12(12), 1063–1073.

    CAS  Google Scholar 

  72. Xie, W., Chipman, J. G., Roberston, D. L., Erikson, R. L., & Simmons, D. L. (1991). Expression of a mitogen-responsive gene encoding prostaglandin synthase is regulated by mRNA splicing. Proceedings of the National Academy of Sciences of the United States of America, 88(7), 2682–2686.

    Article  Google Scholar 

  73. Smith, W. L., & DeWitt, D. L. (1995). Biochemistry of prostaglandin endoperoxide H synthase and their differential susceptibility to nonsteroidal anti-inflammatory drugs. Seminars in Nephrology, 15, 179–194.

    PubMed  CAS  Google Scholar 

  74. Kulmacz, R. J., & Wang, L. H. (1995). Comparison of hydroperoxide initiator requirements for the cyclooxygenase activities of prostaglandin H synthase-1 and -2. Journal of Biological Chemistry, 270, 24019.

    Article  PubMed  CAS  Google Scholar 

  75. Smyth, S. S., Mcever, R. P., Weyrich, A. S., Morrell, C. N., Hoffman, M. R., Arepally, G. M., et al. (2009). Platelet functions beyond hemostasis. Journal of Thrombosis and Haemostasis, 7, 1759–1766.

    Article  PubMed  CAS  Google Scholar 

  76. Li, C., Li, J., Li, Y., Lang, S., Yougbare, I., Zhu, G., et al. (2012). Crosstalk between platelets and the immune system: Old systems with new discoveries. Advances in Hematology, 2012, 384685. Epub 2012 Sep 12.

    Article  PubMed  Google Scholar 

  77. Aslam, R., Speck, E. R., Kim, M., et al. (2006). Platelet Toll-like receptor expression modulates lipopolysaccharide-induced thrombocytopenia and tumor necrosis factor-α production in vivo. Blood, 107(2), 637–641.

    Article  PubMed  CAS  Google Scholar 

  78. Littman, D. R., & Rudensky, A. Y. (2010). Th17 and regulatory T cells in mediating and restraining inflammation. Cell, 140(6), 845–858.

    Article  PubMed  CAS  Google Scholar 

  79. Austrup, F., Vestweber, D., Borges, E., et al. (1997). P- and E-selectin mediate recruitment of T-helper-1 but not T-helper-2 cells into inflamed tissues. Nature, 385(6611), 81–83.

    Article  PubMed  CAS  Google Scholar 

  80. Elzey, B. D., Tian, J., Jensen, R. J., et al. (2003). Platelet-mediated modulation of adaptive immunity: A communication link between innate and adaptive immune compartments. Immunity, 19(1), 9–19.

    Article  PubMed  CAS  Google Scholar 

  81. Kopp, H. G., Placke, T., & Salih, H. R. (2009). Platelet-derived transforming growth factor-β down-regulates NKG2D thereby inhibiting natural killer cell antitumor reactivity. Cancer Research, 69(19), 7775–7783.

    Article  PubMed  CAS  Google Scholar 

  82. Baenziger, N. L., Brodie, G. N., & Majerus, P. W. (1971). A thrombin-sensitive protein of human platelet membranes. Proceedings of the National Academy of Sciences of the United States of America, 68(1), 240–243.

    Article  PubMed  CAS  Google Scholar 

  83. Crawford, S. E., Stellmach, V., Murphy-Ullrich, J. E., et al. (1998). Thrombospondin-1 is a major activator of TGF-β1 in vivo. Cell, 93(7), 1159–1170.

    Article  PubMed  CAS  Google Scholar 

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  1. Section of Cardiology, Department of Cardio-Thoracic and Respiratory Sciences, Second University of Naples, Naples, Italy

    Giovanni Cimmino & Paolo Golino

  2. Division of Cardiology, Second University of Naples, c/o Ospedale S. Sebastiano Via Tescione, 1, 81100, Caserta, Italy

    Paolo Golino

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Cimmino, G., Golino, P. Platelet Biology and Receptor Pathways. J. of Cardiovasc. Trans. Res. 6, 299–309 (2013). https://doi.org/10.1007/s12265-012-9445-9

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