Extracellular microvesicle microRNAs in children with sickle cell anaemia with divergent clinical phenotypes

British Journal of Haematology

Volumn 174, Issue 5, 2016, Pages 786-798

  Khalyfa, Abdelnaby ^a   Khalyfa, Ahamed A ^a   Akbarpour, Mahzad ^a   Connes, Phillippe ^b,c,d,e   Romana, Marc ^b,c   Lapping Carr, Gabrielle ^a   Zhang, Chunling ^f   Andrade, Jorge ^f   Gozal, David ^a  

^a UNIVERSITY OF CHICAGO   (United States)

^b French West Indies University   (Guadeloupe)

^c Laboratoire d'Excellence du Globule Rouge (LABEX GR Ex) PRES Sorbonne   (France)

^d INSTITUT UNIVERSITAIRE DE FRANCE   (France)

^e Univ Lyon University Jean Monnet Saint Etienne   (France)

^f UNIVERSITY OF CHICAGO   (United States)

Author keywords

endothelial function; exosomes; sickle cell anaemia

Indexed keywords

MICRORNA;

ADOLESCENT; ARTICLE; CELL ACTIVATION; CELL ADHESION; CHILD; CHILD HEALTH; CLINICAL ARTICLE; CONTROLLED STUDY; DISEASE COURSE; DISEASE SEVERITY; DNA MICROARRAY; ENDOTHELIUM CELL; EXOSOME; EXTRACELLULAR MICROVESICLE; GENE TARGETING; HUMAN; HUMAN CELL; MEMBRANE MICROPARTICLE; MONOCYTE; MOUSE; NONHUMAN; PHENOTYPE; PRIMARY CELL CULTURE; PRIORITY JOURNAL; QUANTITATIVE ANALYSIS; REAL TIME POLYMERASE CHAIN REACTION; SCHOOL CHILD; SICKLE CELL ANEMIA;

EID: 84987762488     PISSN: 00071048     EISSN: 13652141     Source Type: Journal    
DOI: 10.1111/bjh.14104     Document Type: Article

References (66)

1. Ballas, S.K., Lieff, S., Benjamin, L.J., Dampier, C.D., Heeney, M.M., Hoppe, C., Johnson, C.S., Rogers, Z.R., Smith-Whitley, K., Wang, W.C. & Telen, M.J. for the Comprehensive Sickle Cell Centers Investigators (2010) Definitions of the phenotypic manifestations of sickle cell disease. American Journal of Hematology, 85, 6–13.
2. Baranyai, T., Herczeg, K., Onodi, Z., Voszka, I., Modos, K., Marton, N., Nagy, G., Mager, I., Wood, M.J., El Andaloussi, S., Palinkas, Z., Kumar, V., Nagy, P., Kittel, A., Buzas, E.I., Ferdinandy, P. & Giricz, Z. (2015) Isolation of exosomes from blood plasma: qualitative and quantitative comparison of ultracentrifugation and size exclusion chromatography methods. PLoS ONE, 10, e0145686.
3. Bartel, D.P. (2009) MicroRNAs: target recognition and regulatory functions. Cell, 136, 215–233.
4. Bobrie, A., Colombo, M., Raposo, G. & Thery, C. (2011) Exosome secretion: molecular mechanisms and roles in immune responses. Traffic, 12, 1659–1668.
5. Camus, S.M., Gausseres, B., Bonnin, P., Loufrani, L., Grimaud, L., Charue, D., De Moraes, J.A., Renard, J.M., Tedgui, A., Boulanger, C.M., Tharaux, P.L. & Blanc-Brude, O.P. (2012) Erythrocyte microparticles can induce kidney vaso-occlusions in a murine model of sickle cell disease. Blood, 120, 5050–5058.
6. Camus, S.M., De Moraes, J.A., Bonnin, P., Abbyad, P., Le Jeune, S., Lionnet, F., Loufrani, L., Grimaud, L., Lambry, J.C., Charue, D., Kiger, L., Renard, J.M., Larroque, C., Le Clesiau, H., Tedgui, A., Bruneval, P., Barja-Fidalgo, C., Alexandrou, A., Tharaux, P.L., Boulanger, C.M. & Blanc-Brude, O.P. (2015) Circulating cell membrane microparticles transfer heme to endothelial cells and trigger vasoocclusions in sickle cell disease. Blood, 125, 3805–3814.
7. Chistiakov, D.A., Orekhov, A.N. & Bobryshev, Y.V. (2015) Extracellular vesicles and atherosclerotic disease. Cellular and Molecular Life Sciences, 72, 2697–2708.
8. Colombo, M., Raposo, G. & Thery, C. (2014) Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. Annual Review of Cell and Developmental Biology, 30, 255–289.
9. Connes, P., Lamarre, Y., Waltz, X., Ballas, S.K., Lemonne, N., Etienne-Julan, M., Hue, O., Hardy-Dessources, M.D. & Romana, M. (2014) Haemolysis and abnormal haemorheology in sickle cell anaemia. British Journal of Haematology, 165, 564–572.
10. Cossetti, C., Iraci, N., Mercer, T.R., Leonardi, T., Alpi, E., Drago, D., Alfaro-Cervello, C., Saini, H.K., Davis, M.P., Schaeffer, J., Vega, B., Stefanini, M., Zhao, C., Muller, W., Garcia-Verdugo, J.M., Mathivanan, S., Bachi, A., Enright, A.J., Mattick, J.S. & Pluchino, S. (2014) Extracellular vesicles from neural stem cells transfer IFN-gamma via Ifngr1 to activate Stat1 signaling in target cells. Molecular Cell, 56, 193–204.
11. Dampier, C., Setty, B.N., Eggleston, B., Brodecki, D., O'Neal, P. & Stuart, M. (2004) Vaso-occlusion in children with sickle cell disease: clinical characteristics and biologic correlates. Journal of Pediatric Hematology/oncology, 26, 785–790.
12. Das, S. & Halushka, M.K. (2015) Extracellular vesicle microRNA transfer in cardiovascular disease. Cardiovasc Pathol, 24, 199–206.
13. Dennis, G. Jr, Sherman, B.T., Hosack, D.A., Yang, J., Gao, W., Lane, H.C. & Lempicki, R.A. (2003) DAVID: database for annotation, visualization, and integrated discovery. Genome Biology, 4, P3.
14. Dworkis, D.A., Klings, E.S., Solovieff, N., Li, G., Milton, J.N., Hartley, S.W., Melista, E., Parente, J., Sebastiani, P., Steinberg, M.H. & Baldwin, C.T. (2011) Severe sickle cell anemia is associated with increased plasma levels of TNF-R1 and VCAM-1. American Journal of Hematology, 86, 220–223.
15. Enderle, D., Spiel, A., Coticchia, C.M., Berghoff, E., Mueller, R., Schlumpberger, M., Sprenger-Haussels, M., Shaffer, J.M., Lader, E., Skog, J. & Noerholm, M. (2015) Characterization of RNA from exosomes and other extracellular vesicles isolated by a novel spin column-based method. PLoS ONE, 10, e0136133.
16. Foucan, L., Ekouevi, D., Etienne-Julan, M., Salmi, L.R. & Diara, J.P. & Paediatric Cohort of Guadeloupe. (2006) Early onset dactylitis associated with the occurrence of severe events in children with sickle cell anaemia. The Paediatric Cohort of Guadeloupe (1984-99). Paediatric and Perinatal Epidemiology, 20, 59–66.
17. Gallart-Palau, X., Serra, A., Wong, A.S., Sandin, S., Lai, M.K., Chen, C.P., Kon, O.L. & Sze, S.K. (2015) Extracellular vesicles are rapidly purified from human plasma by PRotein Organic Solvent PRecipitation (PROSPR). Scientific Reports, 5, 14664.
18. Gharib, S.A., Khalyfa, A., Abdelkarim, A., Bhushan, B. & Gozal, D. (2012) Integrative miRNA-mRNA profiling of adipose tissue unravels transcriptional circuits induced by sleep fragmentation. PLoS ONE, 7, e37669.
19. Guo, Z., Wu, R., Gong, J., Zhu, W., Li, Y., Wang, Z., Li, N. & Li, J. (2015) Altered microRNA expression in inflamed and non-inflamed terminal ileal mucosa of adult patients with active Crohn's disease. Journal of Gastroenterology and Hepatology, 30, 109–116.
20. Hebbel, R.P., Vercellotti, G. & Nath, K.A. (2009) A systems biology consideration of the vasculopathy of sickle cell anemia: the need for multi-modality chemo-prophylaxsis. Cardiovasc Hematol Disord Drug Targets, 9, 271–292.
21. Hoefer, I.E., Steffens, S., Ala-Korpela, M., Back, M., Badimon, L., Bochaton-Piallat, M.L., Boulanger, C.M., Caligiuri, G., Dimmeler, S., Egido, J., Evans, P.C., Guzik, T., Kwak, B.R., Landmesser, U., Mayr, M., Monaco, C., Pasterkamp, G., Tunon, J. & Weber, C., on behalf of the ESC Working Group Atherosclerosis and Vascular Biology. (2015) Novel methodologies for biomarker discovery in atherosclerosis. European Heart Journal, 36, 2635–2642.
22. Inati, A., Chabtini, L., Mounayar, M. & Taher, A. (2009) Current understanding in the management of sickle cell disease. Hemoglobin, 33, S107–S115.
23. Ismail, N., Wang, Y., Dakhlallah, D., Moldovan, L., Agarwal, K., Batte, K., Shah, P., Wisler, J., Eubank, T.D., Tridandapani, S., Paulaitis, M.E., Piper, M.G. & Marsh, C.B. (2013) Macrophage microvesicles induce macrophage differentiation and miR-223 transfer. Blood, 121, 984–995.
24. Jakubowski, J.A., Zhou, C., Winters, K.J., Lachno, D.R., Howard, J., Payne, C.D., Mant, T., Jurcevic, S. & Frelinger, A.L. 3rd (2015) The effect of prasugrel on ADP-stimulated markers of platelet activation in patients with sickle cell disease. Platelets, 26, 474–479.
25. Kapustin, A.N., Chatrou, M.L., Drozdov, I., Zheng, Y., Davidson, S.M., Soong, D., Furmanik, M., Sanchis, P., De Rosales, R.T., Alvarez-Hernandez, D., Shroff, R., Yin, X., Muller, K., Skepper, J.N., Mayr, M., Reutelingsperger, C.P., Chester, A., Bertazzo, S., Schurgers, L.J. & Shanahan, C.M. (2015) Vascular smooth muscle cell calcification is mediated by regulated exosome secretion. Circulation Research, 116, 1312–1323.
26. Kasar, M., Boga, C., Yeral, M., Asma, S., Kozanoglu, I. & Ozdogu, H. (2014) Clinical significance of circulating blood and endothelial cell microparticles in sickle-cell disease. Journal of Thrombosis and Thrombolysis, 38, 167–175.
27. Kato, G.J., Gladwin, M.T. & Steinberg, M.H. (2007) Deconstructing sickle cell disease: reappraisal of the role of hemolysis in the development of clinical subphenotypes. Blood Reviews, 21, 37–47.
28. Kato, G.J., Hebbel, R.P., Steinberg, M.H. & Gladwin, M.T. (2009) Vasculopathy in sickle cell disease: Biology, pathophysiology, genetics, translational medicine, and new research directions. American Journal of Hematology, 84, 618–625.
29. Kaymaz, B.T., Gunel, N.S., Ceyhan, M., Cetintas, V.B., Ozel, B., Yandim, M.K., Kipcak, S., Aktan, C., Gokbulut, A.A., Baran, Y. & Can, B.K. (2015) Revealing genome-wide mRNA and microRNA expression patterns in leukemic cells highlighted “hsa-miR-2278” as a tumor suppressor for regain of chemotherapeutic imatinib response due to targeting STAT5A. Tumour Biology, 36, 7915–7927.
30. Kutlar, A. & Embury, S.H. (2014) Cellular adhesion and the endothelium: P-selectin. Hematology/oncology Clinics of North America, 28, 323–339.
31. Kutlar, A., Ataga, K.I., McMahon, L., Howard, J., Galacteros, F., Hagar, W., Vichinsky, E., Cheung, A.T., Matsui, N. & Embury, S.H. (2012) A potent oral P-selectin blocking agent improves microcirculatory blood flow and a marker of endothelial cell injury in patients with sickle cell disease. American Journal of Hematology, 87, 536–539.
32. Lamarre, Y., Romana, M., Waltz, X., Lalanne-Mistrih, M.L., Tressieres, B., Divialle-Doumdo, L., Hardy-Dessources, M.D., Vent-Schmidt, J., Petras, M., Broquere, C., Maillard, F., Tarer, V., Etienne-Julan, M. & Connes, P. (2012) Hemorheological risk factors of acute chest syndrome and painful vaso-occlusive crisis in children with sickle cell disease. Haematologica, 97, 1641–1647.
33. Lasser, C. (2015) Exosomes in diagnostic and therapeutic applications: biomarker, vaccine and RNA interference delivery vehicle. Expert Opin Biol Ther, 15, 103–117.
34. Lo Cicero, A., Stahl, P.D. & Raposo, G. (2015) Extracellular vesicles shuffling intercellular messages: for good or for bad. Current Opinion in Cell Biology, 35, 69–77.
35. Lobb, R.J., Becker, M., Wen, S.W., Wong, C.S., Wiegmans, A.P., Leimgruber, A. & Moller, A. (2015) Optimized exosome isolation protocol for cell culture supernatant and human plasma. J Extracell Vesicles, 4, 27031.
36. Lozano, R., Naghavi, M., Foreman, K., Lim, S., Shibuya, K., Aboyans, V., Abraham, J., Adair, T., Aggarwal, R., Ahn, S.Y., Alvarado, M., Anderson, H.R., Anderson, L.M., Andrews, K.G., Atkinson, C., Baddour, L.M., Barker-Collo, S., Bartels, D.H., Bell, M.L., Benjamin, E.J., Bennett, D., Bhalla, K., Bikbov, B., Bin Abdulhak, A., Birbeck, G., Blyth, F., Bolliger, I., Boufous, S., Bucello, C., Burch, M., Burney, P., Carapetis, J., Chen, H., Chou, D., Chugh, S.S., Coffeng, L.E., Colan, S.D., Colquhoun, S., Colson, K.E., Condon, J., Connor, M.D., Cooper, L.T., Corriere, M., Cortinovis, M., de Vaccaro, K.C., Couser, W., Cowie, B.C., Criqui, M.H., Cross, M., Dabhadkar, K.C., Dahodwala, N., De Leo, D., Degenhardt, L., Delossantos, A., Denenberg, J., Des Jarlais, D.C., Dharmaratne, S.D., Dorsey, E.R., Driscoll, T., Duber, H., Ebel, B., Erwin, P.J., Espindola, P., Ezzati, M., Feigin, V., Flaxman, A.D., Forouzanfar, M.H., Fowkes, F.G., Franklin, R., Fransen, M., Freeman, M.K., Gabriel, S.E., Gakidou, E., Gaspari, F., Gillum, R.F., Gonzalez-Medina, D., Halasa, Y.A., Haring, D., Harrison, J.E., Havmoeller, R., Hay, R.J., Hoen, B., Hotez, P.J., Hoy, D., Jacobsen, K.H., James, S.L., Jasrasaria, R., Jayaraman, S., Johns, N., Karthikeyan, G., Kassebaum, N., Keren, A., Khoo, J.P., Knowlton, L.M., Kobusingye, O., Koranteng, A., Krishnamurthi, R., Lipnick, M., Lipshultz, S.E., Ohno, S.L., Mabweijano, J., MacIntyre, M.F., Mallinger, L., March, L., Marks, G.B., Marks, R., Matsumori, A., Matzopoulos, R., Mayosi, B.M., McAnulty, J.H., McDermott, M.M., McGrath, J., Mensah, G.A., Merriman, T.R., Michaud, C., Miller, M., Miller, T.R., Mock, C., Mocumbi, A.O., Mokdad, A.A., Moran, A., Mulholland, K., Nair, M.N., Naldi, L., Narayan, K.M., Nasseri, K., Norman, P., O'Donnell, M., Omer, S.B., Ortblad, K., Osborne, R., Ozgediz, D., Pahari, B., Pandian, J.D., Rivero, A.P., Padilla, R.P., Perez-Ruiz, F., Perico, N., Phillips, D., Pierce, K., Pope, C.A. 3rd, Porrini, E., Pourmalek, F., Raju, M., Ranganathan, D., Rehm, J.T., Rein, D.B., Remuzzi, G., Rivara, F.P., Roberts, T., De Leon, F.R., Rosenfeld, L.C., Rushton, L., Sacco, R.L., Salomon, J.A., Sampson, U., Sanman, E., Schwebel, D.C., Segui-Gomez, M., Shepard, D.S., Singh, D., Singleton, J., Sliwa, K., Smith, E., Steer, A., Taylor, J.A., Thomas, B., Tleyjeh, I.M., Towbin, J.A., Truelsen, T., Undurraga, E.A., Venketasubramanian, N., Vijayakumar, L., Vos, T., Wagner, G.R., Wang, M., Wang, W., Watt, K., Weinstock, M.A., Weintraub, R., Wilkinson, J.D., Woolf, A.D., Wulf, S., Yeh, P.H., Yip, P., Zabetian, A., Zheng, Z.J., Lopez, A.D., Murray, C.J., AlMazroa, M.A. & Memish, Z.A. (2012) Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet, 380, 2095–2128.
37. Maslanka, K., Uhrynowska, M., Lopacz, P., Wrobel, A., Smolenska-Sym, G., Guz, K., Lachert, E., Ostas, A. & Brojer, E. (2015) Analysis of leucocyte antibodies, cytokines, lysophospholipids and cell microparticles in blood components implicated in post-transfusion reactions with dyspnoea. Vox Sanguinis, 108, 27–36.
38. Mitchell, P.S., Parkin, R.K., Kroh, E.M., Fritz, B.R., Wyman, S.K., Pogosova-Agadjanyan, E.L., Peterson, A., Noteboom, J., O'Briant, K.C., Allen, A., Lin, D.W., Urban, N., Drescher, C.W., Knudsen, B.S., Stirewalt, D.L., Gentleman, R., Vessella, R.L., Nelson, P.S., Martin, D.B. & Tewari, M. (2008) Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci U S A, 105, 10513–10518.
39. Napoli, C., Lerman, L.O., de Nigris, F., Gossl, M., Balestrieri, M.L. & Lerman, A. (2006) Rethinking primary prevention of atherosclerosis-related diseases. Circulation, 114, 2517–2527.
40. Nebor, D., Romana, M., Santiago, R., Vachiery, N., Picot, J., Broquere, C., Chaar, V., Doumdo, L., Odievre, M.H., Benkerrou, M. & Elion, J. (2013) Fetal hemoglobin and hydroxycarbamide moduate both plasma concentration and cellular origin of circulating microparticles in sickle cell anemia children. Haematologica, 98, 862–867.
41. Nebor, D., Bowers, A., Connes, P., Hardy-Dessources, M.D., Knight-Madden, J., Cumming, V., Reid, M. & Romana, M. (2014) Plasma concentration of platelet-derived microparticles is related to painful vaso-occlusive phenotype severity in sickle cell anemia. PLoS ONE, 9, e87243.
42. Nicoloso, M.S., Spizzo, R., Shimizu, M., Rossi, S. & Calin, G.A. (2009) MicroRNAs–the micro steering wheel of tumour metastases. Nature Reviews Cancer, 9, 293–302.
43. Ozdogu, H., Boga, C., Sozer, O., Sezgin, N., Kizilkilic, E., Maytalman, E. & Yalcintas, D. (2007) The apoptosis of blood polymorphonuclear leukocytes in sickle cell disease. Cytometry B Clin Cytom, 72, 276–280.
44. Pegtel, D.M., Cosmopoulos, K., Thorley-Lawson, D.A., van Eijndhoven, M.A., Hopmans, E.S., Lindenberg, J.L., de Gruijl, T.D., Wurdinger, T. & Middeldorp, J.M. (2010) Functional delivery of viral miRNAs via exosomes. Proc Natl Acad Sci U S A, 107, 6328–6333.
45. Piccin, A., Murphy, C., Eakins, E., Kunde, J., Corvetta, D., Di Pierro, A., Negri, G., Guido, M., Sainati, L., Mc Mahon, C., Smith, O.P. & Murphy, W. (2015) Circulating microparticles, protein C, free protein S and endothelial vascular markers in children with sickle cell anaemia. J Extracell Vesicles, 4, 28414.
46. Pigati, L., Yaddanapudi, S.C., Iyengar, R., Kim, D.J., Hearn, S.A., Danforth, D., Hastings, M.L. & Duelli, D.M. (2010) Selective release of microRNA species from normal and malignant mammary epithelial cells. PLoS ONE, 5, e13515.
47. Pitchford, S.C., Furze, R.C., Jones, C.P., Wengner, A.M. & Rankin, S.M. (2009) Differential mobilization of subsets of progenitor cells from the bone marrow. Cell Stem Cell, 4, 62–72.
48. Platt, O.S., Thorington, B.D., Brambilla, D.J., Milner, P.F., Rosse, W.F., Vichinsky, E. & Kinney, T.R. (1991) Pain in sickle cell disease. Rates and risk factors. New England Journal of Medicine, 325, 11–16.
49. Rees, D.C., Williams, T.N. & Gladwin, M.T. (2010) Sickle-cell disease. Lancet, 376, 2018–2031.
50. Robbins, P.D. & Morelli, A.E. (2014) Regulation of immune responses by extracellular vesicles. Nature Reviews Immunology, 14, 195–208.
51. Savina, A., Furlan, M., Vidal, M. & Colombo, M.I. (2003) Exosome release is regulated by a calcium-dependent mechanism in K562 cells. Journal of Biological Chemistry, 278, 20083–20090.
52. Schmittgen, T.D. & Livak, K.J. (2008) Analyzing real-time PCR data by the comparative C(T) method. Nature Protocols, 3, 1101–1108.
53. Simons, M. & Raposo, G. (2009) Exosomes–vesicular carriers for intercellular communication. Current Opinion in Cell Biology, 21, 575–581.
54. Skog, J., Wurdinger, T., van Rijn, S., Meijer, D.H., Gainche, L., Sena-Esteves, M., Curry, W.T. Jr, Carter, B.S., Krichevsky, A.M. & Breakefield, X.O. (2008) Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nature Cell Biology, 10, 1470–1476.
55. Steinberg, M.H. (2005) Predicting clinical severity in sickle cell anaemia. British Journal of Haematology, 129, 465–481.
56. Stuart, M.J. & Nagel, R.L. (2004) Sickle-cell disease. Lancet, 364, 1343–1360.
57. Tantawy, A.A., Adly, A.A., Ismail, E.A., Habeeb, N.M. & Farouk, A. (2013) Circulating platelet and erythrocyte microparticles in young children and adolescents with sickle cell disease: relation to cardiovascular complications. Platelets, 24, 605–614.
58. Tarer, V., Etienne-Julan, M., Diara, J.P., Belloy, M.S., Mukizi-Mukaza, M., Elion, J. & Romana, M. (2006) Sickle cell anemia in Guadeloupean children: pattern and prevalence of acute clinical events. European Journal of Haematology, 76, 193–199.
59. Thery, C., Boussac, M., Veron, P., Ricciardi-Castagnoli, P., Raposo, G., Garin, J. & Amigorena, S. (2001) Proteomic analysis of dendritic cell-derived exosomes: a secreted subcellular compartment distinct from apoptotic vesicles. J Immunol, 166, 7309–7318.
60. Thery, C., Ostrowski, M. & Segura, E. (2009) Membrane vesicles as conveyors of immune responses. Nature Reviews Immunology, 9, 581–593.
61. Tian, T., Wang, Y., Wang, H., Zhu, Z. & Xiao, Z. (2010) Visualizing of the cellular uptake and intracellular trafficking of exosomes by live-cell microscopy. Journal of Cellular Biochemistry, 111, 488–496.
62. van Tits, L.J., van Heerde, W.L., Landburg, P.P., Boderie, M.J., Muskiet, F.A., Jacobs, N., Duits, A.J. & Schnog, J.B. (2009) Plasma annexin A5 and microparticle phosphatidylserine levels are elevated in sickle cell disease and increase further during painful crisis. Biochemical and Biophysical Research Communications, 390, 161–164.
63. Valadi, H., Ekstrom, K., Bossios, A., Sjostrand, M., Lee, J.J. & Lotvall, J.O. (2007) Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nature Cell Biology, 9, 654–659.
64. Vlachos, I.S., Kostoulas, N., Vergoulis, T., Georgakilas, G., Reczko, M., Maragkakis, M., Paraskevopoulou, M.D., Prionidis, K., Dalamagas, T. & Hatzigeorgiou, A.G. (2012) DIANA miRPath v. 2.0: investigating the combinatorial effect of microRNAs in pathways. Nucleic Acids Research, 40, W498–W504.
65. Yanez-Mo, M., Siljander, P.R., Andreu, Z., Zavec, A.B., Borras, F.E., Buzas, E.I., Buzas, K., Casal, E., Cappello, F., Carvalho, J., Colas, E., Cordeiro-da Silva, A., Fais, S., Falcon-Perez, J.M., Ghobrial, I.M., Giebel, B., Gimona, M., Graner, M., Gursel, I., Gursel, M., Heegaard, N.H., Hendrix, A., Kierulf, P., Kokubun, K., Kosanovic, M., Kralj-Iglic, V., Kramer-Albers, E.M., Laitinen, S., Lasser, C., Lener, T., Ligeti, E., Line, A., Lipps, G., Llorente, A., Lotvall, J., Mancek-Keber, M., Marcilla, A., Mittelbrunn, M., Nazarenko, I., Nolte-'t Hoen, E.N., Nyman, T.A., O'Driscoll, L., Olivan, M., Oliveira, C., Pallinger, E., Del Portillo, H.A., Reventos, J., Rigau, M., Rohde, E., Sammar, M., Sanchez-Madrid, F., Santarem, N., Schallmoser, K., Ostenfeld, M.S., Stoorvogel, W., Stukelj, R., Van der Grein, S.G., Vasconcelos, M.H., Wauben, M.H. & De Wever, O. (2015) Biological properties of extracellular vesicles and their physiological functions. J Extracell Vesicles, 4, 27066.
66. Zhang, C. (2010) MicroRNAs in vascular biology and vascular disease. J Cardiovasc Transl Res, 3, 235–240.