Internal and Emergency Medicine

, Volume 8, Issue 4, pp 291–296 | Cite as

Microparticles and microRNAs: new players in the complex field of coagulation

  • Claudia Camaioni
  • Massimo Gustapane
  • Pio Cialdella
  • Roberta Della Bona
  • Luigi Marzio Biasucci
IM - REVIEW

Abstract

Atherosclerosis is a complex process that begins with endothelial dysfunction, and continues with several inflammatory processes leading, eventually, to plaque rupture and formation of arterial thrombus. Increased platelet reactivity and classical coagulation pathways are not the only players of the whole thrombotic process: microparticles (MPs), irregularly shaped small vesicles released from the plasma membrane after cell activation, apoptosis, or exposure to shear stress have been demonstrated to be involved in such a process. MicroRNAs (MiRs), small-non-coding single-strand RNAs acting as post-transcriptional modulator of target gene expression are expressed in the large majority of eukaryotes. MiRs are implicated in several phenomena: control of metabolism, control of cell-differentiation, control of cell-proliferation and control of cell-apoptosis, therefore contributing to physiologic and pathogenic processes in hematologic, genetic, infective and cardiac diseases. Microparticles operate as a delivery system of MiRs, playing an active and important role in processes such as coagulation and thrombosis. These novel findings also suggest MPs and, in particular MIRs, as possible and promising therapeutic targets.

Keywords

Microparticles Thrombosis Coagulation MicroRNA Atherosclerosis 

References

  1. 1.
    Corti R, Fuster V, Badimon JJ (2003) Pathogenetic concepts of acute coronary syndromes. J Am Coll Cardiol 19 41(4 Suppl S):7S–14SGoogle Scholar
  2. 2.
    Morel O, Jesel L, Freyssinet JM, Toti F (2011) Cellular mechanisms underlying the formation of circulating microparticles. Arteriosc Thromb Vasc Biol 31:15–26CrossRefGoogle Scholar
  3. 3.
    Chargaff E, West R (1946) The biological significance of the thromboplastic protein of blood. J Biol Chem 166:189–197PubMedGoogle Scholar
  4. 4.
    Wolf P (1967) The nature and significance of platelet products in human plasma. Br J Haematol 13:269–288PubMedCrossRefGoogle Scholar
  5. 5.
    Freyssinet JM (2003) Cellular microparticles: what are they bad or good for? J Thromb Haemost 1:1655–1662PubMedCrossRefGoogle Scholar
  6. 6.
    Mackman N (2009) On the trail of microparticles. Circ Res 104:925–927PubMedCrossRefGoogle Scholar
  7. 7.
    Martínez MC, Tesse A, Zobairi F, Andriantsitohaina R (2005) Shed membrane microparticles from circulating and vascular cells in regulating vascular function. Am J Physiol Heart Circ Physiol 288:H1004–H1009PubMedCrossRefGoogle Scholar
  8. 8.
    Banfi C, Brioschi M, Wait R et al (2005) Proteome of endothelial cell-derived procoagulant microparticles. Proteomics 5:4443–4455PubMedCrossRefGoogle Scholar
  9. 9.
    Peterson DB, Sander T, Kaul S et al (2008) Comparative proteomic analysis of PAI-1 and TNF-alpha-derived endothelial microparticles. Proteomics 8:2430–2446PubMedCrossRefGoogle Scholar
  10. 10.
    Sander TL, Ou JS, Densmore JC et al (2008) Protein composition of plasminogen activator inhibitor type 1-derived endothelial microparticles. Shock 29:504–511PubMedCrossRefGoogle Scholar
  11. 11.
    Hugel B, Martínez MC, Kunzelmann C, Freyssinet JM (2005) Membrane microparticles: two sides of the coin physiology 20:22–27Google Scholar
  12. 12.
    Piccin A, Murphy WG, Smith OP (2007) Circulating microparticles: pathophysiology and clinical implications. Blood Rev 21:157–171PubMedCrossRefGoogle Scholar
  13. 13.
    Varga-Szabo D, Braun A, Nieswandt B (2009) Calcium signaling in platelets. J Thromb Haemost 7:1057–1066PubMedCrossRefGoogle Scholar
  14. 14.
    Chang CP, Zhao J, Wiedmer T, Sims PJ (1993) Contribution of platelet microparticle formation and granule secretion to the transmembrane migration of phosphatidylserine. J Biol Chem 268:7171–7178PubMedGoogle Scholar
  15. 15.
    Ay C, Freyssinet JM, Sailer T et al (2009) Circulating procoagulant microparticles in patients with venous thromboembolism. Thromb Res 123:724–726PubMedCrossRefGoogle Scholar
  16. 16.
    Morel O, Toti F, Morel N, Freyssinet JM (2009) Microparticles in endothelial cell and vascular homeostasis: are they really noxious? Haematologica 94:313–317PubMedGoogle Scholar
  17. 17.
    Berckmans RJ, Neiuwland R, Boing AN et al (2001) Cell-derived microparticles circulate in healthy humans and support low grade thrombin generation. Thromb Haemost 85:639–646PubMedGoogle Scholar
  18. 18.
    Dvorak HF, Quay SC, Orenstein NS, Dvorak AM, Hahn P, Bitzer AM, Carvalho AC (1981) Tumor shedding and coagulation. Science 212:923–924PubMedCrossRefGoogle Scholar
  19. 19.
    Drake TA, Morrissey JH, Edgington TS (1989) Selective cellular expression of tissue factor in human tissues. Implications for disorders of hemostasis and thrombosis. Am J Pathol 134:1087–1097PubMedGoogle Scholar
  20. 20.
    Giesen PL, Rauch U, Bohrmann B et al (1999) Blood-borne tissue factor: another view of thrombosis. Proc Natl Acad Sci USA A96:2311–2315CrossRefGoogle Scholar
  21. 21.
    Bogdanov VY, Balasubramanian V, Hathcock J, Vele O, Lieb M, Nemerson Y (2003) Alternatively spliced human tissue factor: a circulating, soluble, thrombogenic protein. Nat Med 9:458–462PubMedCrossRefGoogle Scholar
  22. 22.
    Furie B (2009) Pathogenesis of thrombosis. Hematol Am Soc Hematol Educ Program 2009:255–258CrossRefGoogle Scholar
  23. 23.
    Falati S, Liu Q, Gross P et al (2003) Accumulation of tissue factor into developing thrombi in vivo is depended upon microparticle P-selectin glycoprotein ligand 1 and platelet P-selectin. J Exp Med 197:1585–1598PubMedCrossRefGoogle Scholar
  24. 24.
    Eppihimer MJ, Schaub RG (2000) P-Selectin-dependent inhibition of thrombosis during venous stasis. ArteriosclerThrombVasc Biol 20:2483–2488CrossRefGoogle Scholar
  25. 25.
    Morel O, Toti F, Hugel B, Bakouboula B, Camoin-Jau L, Dignat-George F, Freyssinet JM (2006) Procoagulant microparticles: disrupting the vascular homeostasis equation? ArterioscThrombVasc Biol 26:2594–2604Google Scholar
  26. 26.
    Morel O, Pereira B, Averous G et al (2009) Increased levels of procoagulant tissue factor-bearing microparticles within the occluded coronary artery of patients with ST-segment elevation myocardial infarction: role of endothelial damage and leukocyte activation. Atherosclerosis 204:636–641PubMedCrossRefGoogle Scholar
  27. 27.
    Shai E, Varon D (2011) Development, cell differentiation, angiogenesis—microparticles and their roles in angiogenesis. Arteriosc Thromb Vasc Biol 31:10–4. (Review)Google Scholar
  28. 28.
    Bernal-Mizrachi L, Bernal-Mizrach L, W Jy, Fierro C et al (2004) Endothelial microparticles correlate with high-risk angiographic lesions in acute coronary syndromes. Int J Cardiol 97:439–446PubMedCrossRefGoogle Scholar
  29. 29.
    Bulut D, Tuns H, Mugge A (2009) CD31+/Annexin V + microparticles in healthy offsprings of patients with coronary artery disease. Eur J Clin Invest 39:17–22PubMedCrossRefGoogle Scholar
  30. 30.
    Combes V, Simon AC, Grau GE, Arnoux D, Camoin L, Sabatier F, Mutin M, Sanmarco M, Sampol J, Dignat-George F (1999) In vitro generation of endothelial microparticles and possible prothrombotic activity in patients with lupus anticoagulant. J Clin Invest 104:93–102PubMedCrossRefGoogle Scholar
  31. 31.
    Zwicker JI (2010) Predictive value of tissue factor bearing microparticles in cancer associated thrombosis. Thromb Res 125(Suppl 2):S89–S91PubMedCrossRefGoogle Scholar
  32. 32.
    Griffiths-Jones S (2004) The microRNA Registry. Nucleic Acids Res 32:D109–D111PubMedCrossRefGoogle Scholar
  33. 33.
    Hunter MP, Ismail N, Zhang X, et al (2008) Detection of microRNA expression in human peripheral blood microvesicles. PLoS One 3:e3694Google Scholar
  34. 34.
    Poy MN, Eliasson L, Krutzfeldt J, Kuwajima S, Ma X et al (2004) A pancreatic islet-specific microRNA regulates insulin secretion. Nature 432:226–230PubMedCrossRefGoogle Scholar
  35. 35.
    Hatfield S, Ruohola-Baker H (2008) MicroRNA and stem cell function. Cell Tissue Res 331:57–66PubMedCrossRefGoogle Scholar
  36. 36.
    Georgantas RWIII, Hildreth R, Morisot S, Alder J, Liu CG et al (2007) CD34 + hematopoietic stem-progenitor cell microRNA expression and function: a circuit diagram of differentiation control. Proc Natl Acad Sci USA 104:2750–2755PubMedCrossRefGoogle Scholar
  37. 37.
    Valadi H, Ekström K, Bossios A, Sjöstrand M, Lee JJ, Lötvall JO (2007) Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 9:654–659PubMedCrossRefGoogle Scholar
  38. 38.
    Taylor DD, Gercel-Taylor C (2008) MicroRNA signatures of tumor-derived exosomes as diagnostic biomarkers of ovarian cancer. GynecolOncol 110:13–21Google Scholar
  39. 39.
    Fazi F, Rosa A, Fatica A, Gelmetti V, De Marchis ML, Nervi C, Bozzoni I et al (2005) A minicircuitry comprised of microRNA-223 and transcription factors NFI-A and C/EBP alpha regulates human granulopoiesis. Cell 123:819–831PubMedCrossRefGoogle Scholar
  40. 40.
    Johnnidis JB, Harris MH, Wheeler RT, Stehling-Sun S, Lam MH, Kirak O et al (2008) Regulation of progenitor cell proliferation and granulocyte function by microRNA-223. Nature 451:1125–1129PubMedCrossRefGoogle Scholar
  41. 41.
    Lu H, Buchan RJ, Cook SA (2010) MicroRNA-223 regulates GLUT4 expression and cardiomyocyte glucose metabolism. Cardiovasc Res 86:410–420PubMedCrossRefGoogle Scholar
  42. 42.
    Ratajczak J, Wysoczynski M, Hayek F, Janowska-Wieczorek A, Ratajczak MZ MZ et al (2006) Membrane-derived microvesicles: important and underappreciated mediators of cell-to-cell communication. Leukemia 20:1487–1495PubMedCrossRefGoogle Scholar
  43. 43.
    van Niel G, Porto-Carreiro I, Simoes S, Raposo G et al (2006) Exosomes: a common pathway for a specialized function. J Biochem 140:13–21PubMedCrossRefGoogle Scholar
  44. 44.
    Landry P, Plante I, Ouellet DL, Perron MP, Rousseau G, Provost P et al (2009) Existence of a microRNA pathway in anucleate platelets. Nat Struct Mol Biol 6:961–966CrossRefGoogle Scholar
  45. 45.
    Kondkar AA, Bray MS, Leal SM, Nagalla S, Liu DJ, Jin Y, Dong JF, Ren Q, Whiteheart SW, Shaw C, Bray PF et al (2010) VAMP8/endobrevin is overexpressed in hyperreactive human platelets: suggested role for platelet microRNA. J Thromb Haemost 8:369–378PubMedCrossRefGoogle Scholar
  46. 46.
    Arachiche A, Kerbiriou-Nabias D, Garcin I, Letellier T, Dachary-Prigent J (2009) Rapid procoagulant phosphatidylserine exposure relies on high cytosolic calcium rather than on mitochondrial depolarization. Arteriosc Thromb Vasc Biol 29:1883–1889Google Scholar
  47. 47.
    Al-Massarani G, Vacher-Coponat H, Paul P, Arnaud L, Loundou A, Robert S, Moal V, Berland Y, Dignat-George F, Camoin-Jau L et al (2009) Kidney transplantation decreases the level and procoagulant activity of circulating microparticles. Am J Transpl 9:550–557CrossRefGoogle Scholar
  48. 48.
    Bergmeier W, Oh-Hora M, McCarl CA, Roden RC, Bray PF, Feske S et al (2009) R93W mutation in Orai1 causes impaired calcium influx in platelets. Blood 113:675–678PubMedCrossRefGoogle Scholar
  49. 49.
    Hanafusa N, Satonaka H, Doi K, Yatomi Y, Noiri E, Fujita T et al (2010) Platelet-derived microparticles are removed by a membrane plasma separator. ASAIO J 56:323–325PubMedGoogle Scholar
  50. 50.
    Krützfeldt J, Rajewsky N, Braich R, Rajeev KG, Tuschl T, Manoharan M, Stoffel M et al (2005) Silencing of microRNAs in vivo with ‘antagomirs’. Nature 438:685–689PubMedCrossRefGoogle Scholar

Copyright information

© SIMI 2011

Authors and Affiliations

  • Claudia Camaioni
    • 1
  • Massimo Gustapane
    • 1
  • Pio Cialdella
    • 1
  • Roberta Della Bona
    • 1
  • Luigi Marzio Biasucci
    • 1
  1. 1.Institute of CardiologyCatholic University of the Sacred HeartRomeItaly

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