Skip to main content
Log in

Platelet Function in Cardiovascular Disease: Activation of Molecules and Activation by Molecules

  • Published:
Cardiovascular Toxicology Aims and scope Submit manuscript

Abstract

Globally, one of the major causes of death is the cardiovascular disease (CVD), and platelets play an important role in thrombosis and atherosclerosis that led to death. Platelet activation can be done by different molecules, genes, pathways, and chemokines. Lipids activate platelets by inflammatory factors, and platelets are activated by receptors of peptide hormones, signaling and secreted proteins, microRNAs (miRNAs), and oxidative stress which also affect the platelet activation in older age. In addition, surface molecules on platelets can interact with other cells and chemokines in activated platelets and cause inflammation thrombosis events and CVD. However, these molecules activating platelets or being activated by platelets can be suggested as the markers to predict the clinical outcome of CVD and can be targeted to reduce thrombosis and atherosclerosis. However, hindering these molecules by other factors such as genes and receptors can reduce platelet activation and aggregation and targeting these molecules can control platelet interactions, thrombosis, and CVD. In addition, dual therapy with the receptor blockers and novel drugs results in better management of CVD patients. Overall, our review will emphasize on the molecules involved in the activation of platelets and on the molecules that are activated by platelets in CVD and discuss the molecules that can be blocked or targeted to reduce the thrombosis events and control CVD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Fuentes, F., Palomo, I., & Fuentes, E. (2017). Platelet oxidative stress as a novel target of cardiovascular risk in frail older people. Vascular Pharmacology,93, 14–19.

    Article  PubMed  CAS  Google Scholar 

  2. Haybar, H., Khodadi, E., Zibara, K., & Saki, N. (2018). Platelet activation polymorphisms in ischemia. Cardiovascular & Hematological Disorders: Drug Targets,18(2), 153–161.

    Article  CAS  Google Scholar 

  3. Montenont, E., Echagarruga, C., Allen, N., Araldi, E., Suarez, Y., & Berger, J. S. (2016). Platelet WDR1 suppresses platelet activity and associates with cardiovascular disease. Blood,128(16), 2033–2042.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Chatterjee, M., Rath, D., Schlotterbeck, J., Rheinlaender, J., Walker-Allgaier, B., Alnaggar, N., et al. (2017). Regulation of oxidized platelet lipidome: Implications for coronary artery disease. European Heart Journal,38(25), 1993–2005.

    Article  CAS  PubMed  Google Scholar 

  5. Elbatarny, H. S., Netherton, S. J., Ovens, J. D., Ferguson, A. V., & Maurice, D. H. (2007). Adiponectin, ghrelin, and leptin differentially influence human platelet and human vascular endothelial cell functions: Implication in obesity-associated cardiovascular diseases. European Journal of Pharmacology,558(1–3), 7–13.

    Article  CAS  PubMed  Google Scholar 

  6. Lepropre, S., Kautbally, S., Octave, M., Ginion, A., Onselaer, M.-B., Steinberg, G. R., et al. (2018). AMPK-ACC signaling modulates platelet phospholipids and potentiates thrombus formation. Blood,132(11), 1180–1192.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. A Gleissner, C. (2012). Platelet-derived chemokines in atherogenesis: What’s new? Current Vascular Pharmacology,10(5), 563–569.

    Article  PubMed  Google Scholar 

  8. Brandt, E., Ludwig, A., Petersen, F., & Flad, H. D. (2000). Platelet-derived CXC chemokines: Old players in new games. Immunological Reviews,177(1), 204–216.

    Article  CAS  PubMed  Google Scholar 

  9. Masselli, E., Carubbi, C., Pozzi, G., Martini, S., Aversa, F., Galli, D., et al. (2017). Platelet expression of PKCepsilon oncoprotein in myelofibrosis is associated with disease severity and thrombotic risk. Annals of Translational Medicine,5(13), 273.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Parguina, A. F., Grigorian-Shamajian, L., Agra, R. M., Teijeira-Fernandez, E., Rosa, I., Alonso, J., et al. (2010). Proteins involved in platelet signaling are differentially regulated in acute coronary syndrome: A proteomic study. PLoS ONE,5(10), e13404.

    Article  PubMed  CAS  Google Scholar 

  11. Gurbel, P. A., Fox, K. A., Tantry, U. S., ten Cate, H., & Weitz, J. I. (2019). Combination antiplatelet and oral anticoagulant therapy in patients with coronary and peripheral artery disease: Focus on the COMPASS trial. Circulation,139(18), 2170–2185.

    Article  CAS  PubMed  Google Scholar 

  12. Swieringa, F., Spronk, H. M., Heemskerk, J. W., & van der Meijden, P. E. (2018). Integrating platelet and coagulation activation in fibrin clot formation. Research and Practice in Thrombosis and Haemostasis,2(3), 450–460.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Akkerman, J. W. N. (2008). From low-density lipoprotein to platelet activation. The International Journal of Biochemistry & Cell Biology,40(11), 2374–2378.

    Article  CAS  Google Scholar 

  14. Salomon, G. (2012). Structural identification and cardiovascular activities of oxidized phospholipids. Circulation Research,111, 930–946.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Podrez, E. A., Byzova, T. V., Febbraio, M., Salomon, R. G., Ma, Y., Valiyaveettil, M., et al. (2007). Platelet CD36 links hyperlipidemia, oxidant stress and a prothrombotic phenotype. Nature Medicine,13(9), 1086.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Chatterjee, M., von Ungern-Sternberg, S., Seizer, P., Schlegel, F., Büttcher, M., Sindhu, N., et al. (2015). Platelet-derived CXCL12 regulates monocyte function, survival, differentiation into macrophages and foam cells through differential involvement of CXCR4–CXCR7. Cell Death & Disease,6(11), e1989.

    Article  CAS  Google Scholar 

  17. Chatterjee, M., & Gawaz, M. (2013). Platelet-derived CXCL 12 (SDF-1α): Basic mechanisms and clinical implications. Journal of Thrombosis and Haemostasis,11(11), 1954–1967.

    Article  CAS  PubMed  Google Scholar 

  18. Weber, C. (2005). Platelets and chemokines in atherosclerosis: Partners in crime. Circulation Research,96(6), 612–616.

    Article  CAS  PubMed  Google Scholar 

  19. Rath, D., Chatterjee, M., Borst, O., Müller, K., Stellos, K., Mack, A. F., et al. (2013). Expression of stromal cell-derived factor-1 receptors CXCR4 and CXCR7 on circulating platelets of patients with acute coronary syndrome and association with left ventricular functional recovery. European Heart Journal,35(6), 386–394.

    Article  PubMed  CAS  Google Scholar 

  20. Li, X., Zhu, M., Penfold, M. E., Koenen, R. R., Thiemann, A., Heyll, K., et al. (2014). Activation of CXCR7 limits atherosclerosis and improves hyperlipidemia by increasing cholesterol uptake in adipose tissue. Circulation,129(11), 1244–1253.

    Article  CAS  PubMed  Google Scholar 

  21. Stellos, K., Ruf, M., Sopova, K., Kilias, A., Rahmann, A., Stamatelopoulos, K., et al. (2011). Plasma levels of stromal cell-derived factor-1 in patients with coronary artery disease: Effect of clinical presentation and cardiovascular risk factors. Atherosclerosis,219(2), 913–916.

    Article  CAS  PubMed  Google Scholar 

  22. Kile, B. T., Panopoulos, A. D., Stirzaker, R. A., Hacking, D. F., Tahtamouni, L. H., Willson, T. A., et al. (2007). Mutations in the cofilin partner Aip1/Wdr1 cause autoinflammatory disease and macrothrombocytopenia. Blood,110(7), 2371–2380.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Kueh, H. Y., Charras, G. T., Mitchison, T. J., & Brieher, W. M. (2008). Actin disassembly by cofilin, coronin, and Aip1 occurs in bursts and is inhibited by barbed-end cappers. The Journal of Cell Biology,182(2), 341–353.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Rodal, A. A., Tetreault, J. W., Lappalainen, P., Drubin, D. G., & Amberg, D. C. (1999). Aip1p interacts with cofilin to disassemble actin filaments. The Journal of Cell Biology,145(6), 1251–1264.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Chu, S., Becker, R., Berger, P., Bhatt, D., Eikelboom, J., Konkle, B., et al. (2010). Mean platelet volume as a predictor of cardiovascular risk: A systematic review and meta-analysis. Journal of Thrombosis and Haemostasis,8(1), 148–156.

    Article  CAS  PubMed  Google Scholar 

  26. Karpatkin, S. (1969). Heterogeneity of human platelets: II. Functional evidence suggestive of young and old platelets. The Journal of Clinical Investigation,48(6), 1083–1087.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Elbatarny, H. S., & Maurice, D. H. (2005). Leptin-mediated activation of human platelets: Involvement of a leptin receptor and phosphodiesterase 3A-containing cellular signaling complex. American Journal of Physiology-Endocrinology and Metabolism,289(4), E695–E702.

    Article  CAS  PubMed  Google Scholar 

  28. Michelson, A. D., Barnard, M. R., Krueger, L. A., Valeri, C. R., & Furman, M. I. (2001). Circulating monocyte-platelet aggregates are a more sensitive marker of in vivo platelet activation than platelet surface P-selectin: Studies in baboons, human coronary intervention, and human acute myocardial infarction. Circulation,104(13), 1533–1537.

    Article  CAS  PubMed  Google Scholar 

  29. Trovati, M., & Anfossi, G. (2002). Influence of insulin and of insulin resistance on platelet and vascular smooth muscle cell function. Journal of Diabetes and Its Complications,16(1), 35–40.

    Article  PubMed  Google Scholar 

  30. Shoji, T., Koyama, H., Fukumoto, S., Maeno, T., Yokoyama, H., Shinohara, K., et al. (2006). Platelet activation is associated with hypoadiponectinemia and carotid atherosclerosis. Atherosclerosis,188(1), 190–195.

    Article  CAS  PubMed  Google Scholar 

  31. Koyama, H., Maeno, T., Fukumoto, S., Shoji, T., Yamane, T., Yokoyama, H., et al. (2003). Platelet P-selectin expression is associated with atherosclerotic wall thickness in carotid artery in humans. Circulation,108(5), 524–529.

    Article  CAS  PubMed  Google Scholar 

  32. Pereira, J., Soto, M., Palomo, I., Ocqueteau, M., Coetzee, L.-M., Astudillo, S., et al. (2002). Platelet aging in vivo is associated with activation of apoptotic pathways: Studies in a model of suppressed thrombopoiesis in dogs. Thrombosis and Haemostasis,87(05), 905–909.

    Article  CAS  PubMed  Google Scholar 

  33. Pastori, D., Pignatelli, P., Carnevale, R., & Violi, F. (2015). Nox-2 up-regulation and platelet activation: Novel insights. Prostaglandins & Other Lipid Mediators,120, 50–55.

    Article  CAS  Google Scholar 

  34. Dayal, S., Wilson, K. M., Motto, D. G., Miller, F. J., Jr., Chauhan, A. K., & Lentz, S. R. (2013). Hydrogen peroxide promotes aging-related platelet hyperactivation and thrombosis. Circulation,127, 1308–1316.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Fuentes, E., & Palomo, I. (2016). Role of oxidative stress on platelet hyperreactivity during aging. Life Sciences,148, 17–23.

    Article  CAS  PubMed  Google Scholar 

  36. Carnevale, R., Loffredo, L., Pignatelli, P., Nocella, C., Bartimoccia, S., Di Santo, S., et al. (2012). Dark chocolate inhibits platelet isoprostanes via NOX2 down-regulation in smokers. Journal of Thrombosis and Haemostasis,10(1), 125–132.

    Article  CAS  PubMed  Google Scholar 

  37. Mangiacapra, F., De Bruyne, B., Muller, O., Trana, C., Ntalianis, A., Bartunek, J., et al. (2010). High residual platelet reactivity after clopidogrel: Extent of coronary atherosclerosis and periprocedural myocardial infarction in patients with stable angina undergoing percutaneous coronary intervention. Cardiovascular Interventions.,3(1), 35–40.

    Article  PubMed  Google Scholar 

  38. Parodi, G., Marcucci, R., Valenti, R., Gori, A. M., Migliorini, A., Giusti, B., et al. (2011). High residual platelet reactivity after clopidogrel loading and long-term cardiovascular events among patients with acute coronary syndromes undergoing PCI. JAMA,306(11), 1215–1223.

    Article  CAS  PubMed  Google Scholar 

  39. Flierl, U., Bauersachs, J., & Schäfer, A. (2015). Modulation of platelet and monocyte function by the chemokine fractalkine (CX 3 CL 1) in cardiovascular disease. European Journal of Clinical Investigation,45(6), 624–633.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  41. Lievens, D., & von Hundelshausen, P. (2011). Platelets in atherosclerosis. Thrombosis and Haemostasis,105(05), 827–838.

    Google Scholar 

  42. Langer, H. F., Bigalke, B., Seizer, P., Stellos, K., Fateh-Moghadam, S., Gawaz, M. (2010). Interaction of platelets and inflammatory endothelium in the development and progression of coronary artery disease. In Seminars in thrombosis and hemostasis. Thieme Medical Publishers.

  43. Schäfer, A., Schulz, C., Fraccarollo, D., et al. (2007). The CX3C chemokine fractalkine induces vascular dysfunction by generation of superoxide anions. Arteriosclerosis, Thrombosis, and Vascular Biology,27, 55–62.

    Article  PubMed  CAS  Google Scholar 

  44. Schulz, C., Schäfer, A., Stolla, M., et al. (2007). Chemokine fractalkine mediates leukocyte recruitment to inflammatory endothelial cells in flowing whole blood, a critical role for P-selectin expressed on activated platelets. Circulation,116, 764–773.

    Article  CAS  PubMed  Google Scholar 

  45. Schäfer, A., Schulz, C., Eigenthaler, M., Fraccarollo, D., Kobsar, A., Gawaz, M., et al. (2004). Novel role of the membrane-bound chemokine fractalkine in platelet activation and adhesion. Blood,103(2), 407–412.

    Article  PubMed  CAS  Google Scholar 

  46. Postea, O., Vasina, E. M., Cauwenberghs, S., et al. (2012). Contribution of platelet CX(3)CR1 to platelet-monocyte complex formation and vascular recruitment during hyperlipidemia. Arteriosclerosis, Thrombosis, and Vascular Biology,32, 1186–1193.

    Article  CAS  PubMed  Google Scholar 

  47. Flierl, U., Fraccarollo, D., Lausenmeyer, E., Rosenstock, T., Schulz, C., Massberg, S., et al. (2012). Fractalkine activates a signal transduction pathway similar to P2Y12 and is associated with impaired clopidogrel responsiveness. Arteriosclerosis, Thrombosis, and Vascular Biology,32(8), 1832–1840.

    Article  CAS  PubMed  Google Scholar 

  48. García, Á., Senis, Y. A., Antrobus, R., Hughes, C. E., Dwek, R. A., Watson, S. P., et al. (2006). A global proteomics approach identifies novel phosphorylated signaling proteins in GPVI-activated platelets: Involvement of G6f, a novel platelet Grb2-binding membrane adapter. Proteomics,6(19), 5332–5343.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Senis, Y. A., Antrobus, R., Severin, S., Parguina, A. F., Rosa, I., Zitzmann, N., et al. (2009). Proteomic analysis of integrin αIIbβ3 outside-in signaling reveals Src-kinase-independent phosphorylation of Dok-1 and Dok-3 leading to SHIP-1 interactions. Journal of Thrombosis and Haemostasis,7(10), 1718–1726.

    Article  CAS  PubMed  Google Scholar 

  50. Tadokoro, S., Shattil, S. J., Eto, K., Tai, V., Liddington, R. C., de Pereda, J. M., et al. (2003). Talin binding to integrin ß tails: A final common step in integrin activation. Science,302(5642), 103–106.

    Article  CAS  PubMed  Google Scholar 

  51. Honda, S., Shirotani-Ikejima, H., Tadokoro, S., Maeda, Y., Kinoshita, T., Tomiyama, Y., et al. (2009). Integrin-linked kinase associated with integrin activation. Blood,113(21), 5304–5313.

    Article  CAS  PubMed  Google Scholar 

  52. Legate, K. R., Montañez, E., Kudlacek, O., & Füssler, R. (2006). ILK, PINCH and parvin: The tIPP of integrin signalling. Nature Reviews Molecular Cell Biology,7(1), 20.

    Article  CAS  PubMed  Google Scholar 

  53. Tucker, K. L., Sage, T., Stevens, J. M., Jordan, P. A., Jones, S., Barrett, N. E., et al. (2008). A dual role for integrin-linked kinase in platelets: Regulating integrin function and α-granule secretion. Blood,112(12), 4523–4531.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Mallat, Z., Benamer, H., Hugel, B., Benessiano, J., Steg, P. G., Freyssinet, J. M., et al. (2000). Elevated levels of shed membrane microparticles with procoagulant potential in the peripheral circulating blood of patients with acute coronary syndromes. Circulation,101(8), 841–843.

    Article  CAS  PubMed  Google Scholar 

  55. Brill, A., Dashevsky, O., Rivo, J., Gozal, Y., & Varon, D. (2005). Platelet-derived microparticles induce angiogenesis and stimulate post-ischemic revascularization. Cardiovascular Research,67(1), 30–38.

    Article  CAS  PubMed  Google Scholar 

  56. Coppinger, J. A., Cagney, G., Toomey, S., Kislinger, T., Belton, O., McRedmond, J. P., et al. (2004). Characterization of the proteins released from activated platelets leads to localization of novel platelet proteins in human atherosclerotic lesions. Blood,103(6), 2096–2104.

    Article  CAS  PubMed  Google Scholar 

  57. Dobaczewski, M., Gonzalez-Quesada, C., & Frangogiannis, N. G. (2010). The extracellular matrix as a modulator of the inflammatory and reparative response following myocardial infarction. Journal of Molecular and Cellular Cardiology,48(3), 504–511.

    Article  CAS  PubMed  Google Scholar 

  58. Schellings, M. W., Vanhoutte, D., Swinnen, M., Cleutjens, J. P., Debets, J., van Leeuwen, R. E., et al. (2009). Absence of SPARC results in increased cardiac rupture and dysfunction after acute myocardial infarction. Journal of Experimental Medicine,206(1), 113–123.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Shahjahani, M., Khodadi, E., Seghatoleslami, M., Asl, J. M., Golchin, N., Zaieri, Z. D., et al. (2015). Rare cytogenetic abnormalities and alteration of microRNAs in acute myeloid leukemia and response to therapy. Oncology Reviews,9(1), 261.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  60. Khodadi, E., Asnafi, A. A., Mohammadi-Asl, J., Hosseini, S. A., Malehi, A. S., & Saki, N. (2017). Evaluation of miR-21 and miR-150 expression in immune thrombocytopenic purpura pathogenesis: A case-control study. Frontiers in Biology,12(5), 361–369.

    Article  CAS  Google Scholar 

  61. Yao, R., Ma, Y., Du, Y., Liao, M., Li, H., Liang, W., et al. (2011). The altered expression of inflammation-related microRNAs with microRNA-155 expression correlates with Th17 differentiation in patients with acute coronary syndrome. Cellular & Molecular Immunology,8(6), 486.

    Article  CAS  Google Scholar 

  62. Gatsiou, A., Boeckel, J. N., Randriamboavonjy, V., & Stellos, K. (2012). MicroRNAs in platelet biogenesis and function: Implications in vascular homeostasis and inflammation. Current Vascular Pharmacology,10(5), 524–531.

    Article  CAS  PubMed  Google Scholar 

  63. Widera, C., Gupta, S. K., Lorenzen, J. M., Bang, C., Bauersachs, J., Bethmann, K., et al. (2011). Diagnostic and prognostic impact of six circulating microRNAs in acute coronary syndrome. Journal of Molecular and Cellular Cardiology,51(5), 872–875.

    Article  CAS  PubMed  Google Scholar 

  64. Siasos, G., Kollia, C., Tsigkou, V., Basdra, E. K., Lymperi, M., Oikonomou, E., et al. (2013). MicroRNAs: Novel diagnostic and prognostic biomarkers in atherosclerosis. Current Topics in Medicinal Chemistry,13(13), 1503–1517.

    Article  CAS  PubMed  Google Scholar 

  65. Bartel, D. P. (2009). MicroRNAs: Target recognition and regulatory functions. Cell,136(2), 215–233.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Onselaer, M. B., Oury, C., Hunter, R., Eeckhoudt, S., Barile, N., Lecut, C., et al. (2014). The Ca2 +/calmodulin-dependent kinase kinase β-AMP-activated protein kinase-α1 pathway regulates phosphorylation of cytoskeletal targets in thrombin-stimulated human platelets. Journal of Thrombosis and Haemostasis,12(6), 973–986.

    Article  CAS  PubMed  Google Scholar 

  67. Pula, G., Schuh, K., Nakayama, K., Nakayama, K. I., Walter, U., & Poole, A. W. (2006). PKCδ regulates collagen-induced platelet aggregation through inhibition of VASP-mediated filopodia formation. Blood,108(13), 4035–4044.

    Article  CAS  PubMed  Google Scholar 

  68. Pitsilos, S., Hunt, J., Mohler, E. R., Prabhakar, A. M., Poncz, M., Dawicki, J., et al. (2003). Platelet factor 4 localization in carotid atherosclerotic plaques: Correlation with clinical parameters. Thrombosis and Haemostasis,89(06), 1112–1120.

    Article  CAS  Google Scholar 

  69. Von Hundelshausen, P., Koenen, R. R., Sack, M., Mause, S. F., Adriaens, W., Proudfoot, A. E., et al. (2005). Heterophilic interactions of platelet factor 4 and RANTES promote monocyte arrest on endothelium. Blood,105(3), 924–930.

    Article  CAS  Google Scholar 

  70. Scheuerer, B., Ernst, M., Dürrbaum-Landmann, I., Fleischer, J., Grage-Griebenow, E., Brandt, E., et al. (2000). The CXC-chemokine platelet factor 4 promotes monocyte survival and induces monocyte differentiation into macrophages. Blood,95(4), 1158–1166.

    Article  CAS  PubMed  Google Scholar 

  71. Von Hundelshausen, P., Weber, K. S., Huo, Y., Proudfoot, A. E., Nelson, P. J., Ley, K., et al. (2001). RANTES deposition by platelets triggers monocyte arrest on inflamed and atherosclerotic endothelium. Circulation,103(13), 1772–1777.

    Article  Google Scholar 

  72. Smith, D. F., Galkina, E., Ley, K., & Huo, Y. (2005). GRO family chemokines are specialized for monocyte arrest from flow. American Journal of Physiology-Heart and Circulatory Physiology,289(5), H1976–H1984.

    Article  CAS  PubMed  Google Scholar 

  73. Abi-Younes, S., Sauty, A., Mach, F., Sukhova, G., Libby, P., & Luster, A. (2000). The stromal cell–derived factor-1 chemokine is a potent platelet agonist highly expressed in atherosclerotic plaques. Circulation Research,86(2), 131–138.

    Article  CAS  PubMed  Google Scholar 

  74. Abi-Younes, S., Si-Tahar, M., & Luster, A. D. (2001). The CC chemokines MDC and TARC induce platelet activation via CCR4. Thrombosis Research,101(4), 279–289.

    Article  CAS  PubMed  Google Scholar 

  75. Gear, A. R., & Camerini, D. (2003). Platelet chemokines and chemokine receptors: Linking hemostasis, inflammation, and host defense. Microcirculation,10(3–4), 335–350.

    Article  CAS  PubMed  Google Scholar 

  76. Lippi, G., Franchini, M., & Targher, G. (2011). Arterial thrombus formation in cardiovascular disease. Nature Reviews Cardiology,8(9), 502.

    Article  PubMed  Google Scholar 

  77. Strehl, A., Munnix, I. C., Kuijpers, M. J., van der Meijden, P. E., Cosemans, J. M., Feijge, M. A., et al. (2007). Dual role of platelet protein kinase C in thrombus formation stimulation OF pro-aggregatory and suppression of procoagulant activity in plateletS. Journal of Biological Chemistry,282(10), 7046–7055.

    Article  CAS  PubMed  Google Scholar 

  78. Masselli, E., Carubbi, C., Gobbi, G., Mirandola, P., Galli, D., Martini, S., et al. (2015). Protein kinase Cɛ inhibition restores megakaryocytic differentiation of hematopoietic progenitors from primary myelofibrosis patients. Leukemia,29(11), 2192.

    Article  CAS  PubMed  Google Scholar 

  79. Dann, R., Hadi, T., Montenont, E., Boytard, L., Alebrahim, D., Feinstein, J., et al. (2018). Platelet-derived MRP-14 induces monocyte activation in patients with symptomatic peripheral artery disease. Journal of the American College of Cardiology,71(1), 53–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Huo, Y., Schober, A., Forlow, S. B., Smith, D. F., Hyman, M. C., Jung, S., et al. (2003). Circulating activated platelets exacerbate atherosclerosis in mice deficient in apolipoprotein E. Nature Medicine,9(1), 61.

    Article  CAS  PubMed  Google Scholar 

  81. Vorchheimer, D. A., Becker, R., eds. (2006). Platelets in atherothrombosis. Mayo Clinic Proceedings; Elsevier.

  82. Wang, Y., Fang, C., Gao, H., Bilodeau, M. L., Zhang, Z., Croce, K., et al. (2014). Platelet-derived S100 family member myeloid-related protein-14 regulates thrombosis. The Journal of Clinical Investigation,124(5), 2160–2171.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Liu, G., Liang, B., Song, X., Bai, R., Qin, W., Sun, X., et al. (2016). P-selectin increases angiotensin II-induced cardiac inflammation and fibrosis via platelet activation. Molecular Medicine Reports,13(6), 5021–5028.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Edelstein, L. C., Simon, L. M., Montoya, R. T., Holinstat, M., Chen, E. S., Bergeron, A., et al. (2013). Racial differences in human platelet PAR4 reactivity reflect expression of PCTP and miR-376c. Nature Medicine,19(12), 1609.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Rao, A. K. (2017). Transcription factor RUNX1 regulates platelet PCTP (phosphatidylcholine transfer protein): Implications for cardiovascular events. Circulation,136(10), 927–939.

    Article  PubMed  PubMed Central  Google Scholar 

  86. Lonial, S., Waller, E. K., Richardson, P. G., Jagannath, S., Orlowski, R. Z., Giver, C. R., et al. (2005). Risk factors and kinetics of thrombocytopenia associated with bortezomib for relapsed, refractory multiple myeloma. Blood,106, 3777–3784.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Nayak, M. K., Kulkarni, P. P., & Dash, D. (2013). Regulatory role of proteasome in determination of platelet life span. Journal of Biological Chemistry,288(10), 6826–6834.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Shen, Y., Zhou, X., Wang, Z., Yang, G., Jiang, Y., Sun, C., et al. (2011). Coagulation profiles and thromboembolic events of bortezomib plus thalidomide and dexamethasone therapy in newly diagnosed multiple myeloma. Leukemia Research,35, 147–151.

    Article  CAS  PubMed  Google Scholar 

  89. Gupta, N., Li, W., Willard, B., Silverstein, R. L., & McIntyre, T. M. (2014). Proteasome proteolysis supports stimulated platelet function and thrombosis. Arteriosclerosis, Thrombosis, and Vascular Biology,34(1), 160–168.

    Article  CAS  PubMed  Google Scholar 

  90. Gurbel, P. A., & Tantry, U. S. (2010). Combination antithrombotic therapies. Circulation,121, 569–583.

    Article  PubMed  Google Scholar 

  91. Gibson, C. M., Chakrabarti, A. K., Mega, J., Bode, C., Bassand, J.-P., Verheugt, F. W., et al. (2013). Reduction of stent thrombosis in patients with acute coronary syndromes treated with rivaroxaban in ATLAS-ACS 2 TIMI 51. Journal of the American College of Cardiology,62(4), 286–290.

    Article  CAS  PubMed  Google Scholar 

  92. Bhatt, D. L., Fox, K. A., Hacke, W., Berger, P. B., Black, H. R., Boden, W. E., et al. (2006). Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events. New England Journal of Medicine,354(16), 1706–1717.

    Article  CAS  PubMed  Google Scholar 

  93. Bonaca, M. P., Bhatt, D. L., Cohen, M., Steg, P. G., Storey, R. F., Jensen, E. C., et al. (2015). Long-term use of ticagrelor in patients with prior myocardial infarction. New England Journal of Medicine,372(19), 1791–1800.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

We wish to thank all our colleagues in Research Center of Thalassemia & Hemoglobinopathy, Health research institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

Funding

Funding resources were not applicable to this study.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Elahe Khodadi.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Handling Editor: Y. James Kang.

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Khodadi, E. Platelet Function in Cardiovascular Disease: Activation of Molecules and Activation by Molecules. Cardiovasc Toxicol 20, 1–10 (2020). https://doi.org/10.1007/s12012-019-09555-4

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12012-019-09555-4

Keywords

Navigation