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DOI: 10.1055/s-0037-1599081
Extracellular Vesicles in the Antiphospholipid Syndrome
Publikationsverlauf
Publikationsdatum:
05. Mai 2017 (online)
![](https://www.thieme-connect.de/media/sth/201805/lookinside/thumbnails/10-1055-s-0037-1599081_02439-1.jpg)
Abstract
Antiphospholipid antibodies (aPL), particularly those directed against β2-glycoprotein I, cause activation of vascular cells (endothelial cells, platelets, monocytes) and release of extracellular vesicles (EVs), which include exosomes and microparticles (MPs). MPs, particularly endothelial MPs, have been most extensively studied in antiphospholipid syndrome (APS). Compared with healthy controls, patients with aPL have significantly higher levels of circulating endothelial and platelet MPs, including MPs expressing immunological and functional tissue factor. Although a consistent relationship of EVs with APS-related thrombosis and obstetric events has not yet been demonstrated, elevated levels of MPs occurring remote from thrombotic events suggest a chronic state of vascular activation in APS. In addition to being a marker of cellular activation, EVs express bioactive lipids, proteins, and nucleic acids, particularly microribonucleic acid (microRNA). EVs may potentially play a pathogenic role in APS by stimulating thrombosis through tissue factor-dependent and independent mechanisms and by promoting vascular activation. Further research is needed to understand these mechanisms and to determine whether EVs may be a useful biomarker to identify patients with aPL at highest risk of clinical events.
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References
- 1 Giannakopoulos B, Passam F, Rahgozar S, Krilis SA. Current concepts on the pathogenesis of the antiphospholipid syndrome. Blood 2007; 109 (02) 422-430
- 2 Chaturvedi S, McCrae KR. Recent advances in the antiphospholipid antibody syndrome. Curr Opin Hematol 2014; 21 (05) 371-379
- 3 Miyakis S, Lockshin MD, Atsumi T. , et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost 2006; 4 (02) 295-306
- 4 Cervera R, Piette JC, Font J. , et al; Euro-Phospholipid Project Group. Antiphospholipid syndrome: clinical and immunologic manifestations and patterns of disease expression in a cohort of 1,000 patients. Arthritis Rheum 2002; 46 (04) 1019-1027
- 5 Asherson RA, Cervera R, de Groot PG. , et al; Catastrophic Antiphospholipid Syndrome Registry Project Group. Catastrophic antiphospholipid syndrome: international consensus statement on classification criteria and treatment guidelines. Lupus 2003; 12 (07) 530-534
- 6 Cervera R, Serrano R, Pons-Estel GJ. , et al; Euro-Phospholipid Project Group (European Forum on Antiphospholipid Antibodies). Morbidity and mortality in the antiphospholipid syndrome during a 10-year period: a multicentre prospective study of 1000 patients. Ann Rheum Dis 2015; 74 (06) 1011-1018
- 7 Cervera R, Espinosa G. Update on the catastrophic antiphospholipid syndrome and the “CAPS Registry.”. Semin Thromb Hemost 2012; 38 (04) 333-338
- 8 Bucciarelli S, Espinosa G, Cervera R. The CAPS Registry: morbidity and mortality of the catastrophic antiphospholipid syndrome. Lupus 2009; 18 (10) 905-912
- 9 Gebhart J, Posch F, Koder S. , et al. Increased mortality in patients with the lupus anticoagulant: the Vienna Lupus Anticoagulant and Thrombosis Study (LATS). Blood 2015; 125 (22) 3477-3483
- 10 Urbanus RT, de Laat B. Antiphospholipid antibodies and the protein C pathway. Lupus 2010; 19 (04) 394-399
- 11 Rossetto V, Spiezia L, Franz F. , et al. The role of antiphospholipid antibodies toward the protein C/protein S system in venous thromboembolic disease. Am J Hematol 2009; 84 (09) 594-596
- 12 Wahl D, Membre A, Perret-Guillaume C, Regnault V, Lecompte T. Mechanisms of antiphospholipid-induced thrombosis: effects on the protein C system. Curr Rheumatol Rep 2009; 11 (01) 77-81
- 13 Esmon CT. The anticoagulant and anti-inflammatory roles of the protein C anticoagulant pathway. J Autoimmun 2000; 15 (02) 113-116
- 14 Marciniak E, Romond EH. Impaired catalytic function of activated protein C: a new in vitro manifestation of lupus anticoagulant. Blood 1989; 74 (07) 2426-2432
- 15 Borrell M, Sala N, de Castellarnau C, Lopez S, Gari M, Fontcuberta J. Immunoglobulin fractions isolated from patients with antiphospholipid antibodies prevent the inactivation of factor Va by activated protein C on human endothelial cells. Thromb Haemost 1992; 68 (03) 268-272
- 16 de Laat B, Eckmann CM, van Schagen M, Meijer AB, Mertens K, van Mourik JA. Correlation between the potency of a beta2-glycoprotein I-dependent lupus anticoagulant and the level of resistance to activated protein C. Blood Coagul Fibrinolysis 2008; 19 (08) 757-764
- 17 Galli M, Willems GM, Rosing J. , et al. Anti-prothrombin IgG from patients with anti-phospholipid antibodies inhibits the inactivation of factor Va by activated protein C. Br J Haematol 2005; 129 (02) 240-247
- 18 Nojima J, Kuratsune H, Suehisa E, Iwatani Y, Kanakura Y. Acquired activated protein C resistance associated with IgG antibodies against beta2-glycoprotein I and prothrombin as a strong risk factor for venous thromboembolism. Clin Chem 2005; 51 (03) 545-552
- 19 Izumi T, Pound ML, Su Z, Iverson GM, Ortel TL. Anti-beta(2)-glycoprotein I antibody-mediated inhibition of activated protein C requires binding of beta(2)-glycoprotein I to phospholipids. Thromb Haemost 2002; 88 (04) 620-626
- 20 Smirnov MD, Triplett DT, Comp PC, Esmon NL, Esmon CT. On the role of phosphatidylethanolamine in the inhibition of activated protein C activity by antiphospholipid antibodies. J Clin Invest 1995; 95 (01) 309-316
- 21 Shibata S, Harpel PC, Gharavi A, Rand J, Fillit H. Autoantibodies to heparin from patients with antiphospholipid antibody syndrome inhibit formation of antithrombin III-thrombin complexes. Blood 1994; 83 (09) 2532-2540
- 22 Liestøl S, Sandset PM, Jacobsen EM, Mowinckel MC, Wisløff F. Decreased anticoagulant response to tissue factor pathway inhibitor type 1 in plasmas from patients with lupus anticoagulants. Br J Haematol 2007; 136 (01) 131-137
- 23 Bu C, Gao L, Xie W. , et al. beta2-glycoprotein i is a cofactor for tissue plasminogen activator-mediated plasminogen activation. Arthritis Rheum 2009; 60 (02) 559-568
- 24 Rand JH, Wu XX, Quinn AS. , et al. Human monoclonal antiphospholipid antibodies disrupt the annexin A5 anticoagulant crystal shield on phospholipid bilayers: evidence from atomic force microscopy and functional assay. Am J Pathol 2003; 163 (03) 1193-1200
- 25 Rand JH, Wu XX, Quinn AS, Chen PP, Hathcock JJ, Taatjes DJ. Hydroxychloroquine directly reduces the binding of antiphospholipid antibody-beta2-glycoprotein I complexes to phospholipid bilayers. Blood 2008; 112 (05) 1687-1695
- 26 Hulstein JJ, Lenting PJ, de Laat B, Derksen RH, Fijnheer R, de Groot PG. beta2-Glycoprotein I inhibits von Willebrand factor dependent platelet adhesion and aggregation. Blood 2007; 110 (05) 1483-1491
- 27 Giannakopoulos B, Krilis SA. The pathogenesis of the antiphospholipid syndrome. N Engl J Med 2013; 368 (11) 1033-1044
- 28 Simantov R, LaSala JM, Lo SK. , et al. Activation of cultured vascular endothelial cells by antiphospholipid antibodies. J Clin Invest 1995; 96 (05) 2211-2219
- 29 Zhang J, McCrae KR. Annexin A2 mediates endothelial cell activation by antiphospholipid/anti-beta2 glycoprotein I antibodies. Blood 2005; 105 (05) 1964-1969
- 30 Del Papa N, Guidali L, Sala A. , et al. Endothelial cells as target for antiphospholipid antibodies. Human polyclonal and monoclonal anti-beta 2-glycoprotein I antibodies react in vitro with endothelial cells through adherent beta 2-glycoprotein I and induce endothelial activation. Arthritis Rheum 1997; 40 (03) 551-561
- 31 Branch DW, Rodgers GM. Induction of endothelial cell tissue factor activity by sera from patients with antiphospholipid syndrome: a possible mechanism of thrombosis. Am J Obstet Gynecol 1993; 168 (1 Pt 1): 206-210
- 32 Mineo C. Inhibition of nitric oxide and antiphospholipid antibody-mediated thrombosis. Curr Rheumatol Rep 2013; 15 (05) 324
- 33 Allen KL, Fonseca FV, Betapudi V, Willard B, Zhang J, McCrae KR. A novel pathway for human endothelial cell activation by antiphospholipid/anti-b2 glycoprotein I antibodies. Blood 2012; 119 (03) 884-893
- 34 Ramesh S, Morrell CN, Tarango C. , et al. Antiphospholipid antibodies promote leukocyte-endothelial cell adhesion and thrombosis in mice by antagonizing eNOS via b2GPI and apoER2. J Clin Invest 2011; 121 (01) 120-131
- 35 Wu M, Barnard J, Kundu S, McCrae KR. A novel pathway of cellular activation mediated by antiphospholipid antibody-induced extracellular vesicles. J Thromb Haemost 2015; 13 (10) 1928-1940
- 36 Pierangeli SS, Vega-Ostertag ME, Raschi E. , et al. Toll-like receptor and antiphospholipid mediated thrombosis: in vivo studies. Ann Rheum Dis 2007; 66 (10) 1327-1333
- 37 Romay-Penabad Z, Montiel-Manzano MG, Shilagard T. , et al. Annexin A2 is involved in antiphospholipid antibody-mediated pathogenic effects in vitro and in vivo. Blood 2009; 114 (14) 3074-3083
- 38 Romay-Penabad Z, Aguilar-Valenzuela R, Urbanus RT. , et al. Apolipoprotein E receptor 2 is involved in the thrombotic complications in a murine model of the antiphospholipid syndrome. Blood 2011; 117 (04) 1408-1414
- 39 Montiel-Manzano G, Romay-Penabad Z, Papalardo de Martínez E. , et al. In vivo effects of an inhibitor of nuclear factor-kappa B on thrombogenic properties of antiphospholipid antibodies. Ann N Y Acad Sci 2007; 1108: 540-553
- 40 Sorice M, Longo A, Capozzi A. , et al. Anti-beta2-glycoprotein I antibodies induce monocyte release of tumor necrosis factor alpha and tissue factor by signal transduction pathways involving lipid rafts. Arthritis Rheum 2007; 56 (08) 2687-2697
- 41 Vega-Ostertag M, Harris EN, Pierangeli SS. Intracellular events in platelet activation induced by antiphospholipid antibodies in the presence of low doses of thrombin. Arthritis Rheum 2004; 50 (09) 2911-2919
- 42 Pennings MT, Derksen RH, van Lummel M. , et al. Platelet adhesion to dimeric beta-glycoprotein I under conditions of flow is mediated by at least two receptors: glycoprotein Ibalpha and apolipoprotein E receptor 2′. J Thromb Haemost 2007; 5 (02) 369-377
- 43 Shi T, Giannakopoulos B, Yan X. , et al. Anti-beta2-glycoprotein I antibodies in complex with beta2-glycoprotein I can activate platelets in a dysregulated manner via glycoprotein Ib-IX-V. Arthritis Rheum 2006; 54 (08) 2558-2567
- 44 Mulla MJ, Brosens JJ, Chamley LW. , et al. Antiphospholipid antibodies induce a pro-inflammatory response in first trimester trophoblast via the TLR4/MyD88 pathway. Am J Reprod Immunol 2009; 62 (02) 96-111
- 45 van der Pol E, Böing AN, Gool EL, Nieuwland R. Recent developments in the nomenclature, presence, isolation, detection and clinical impact of extracellular vesicles. J Thromb Haemost 2016; 14 (01) 48-56
- 46 György B, Szabó TG, Pásztói M. , et al. Membrane vesicles, current state-of-the-art: emerging role of extracellular vesicles. Cell Mol Life Sci 2011; 68 (16) 2667-2688
- 47 Lynch SF, Ludlam CA. Plasma microparticles and vascular disorders. Br J Haematol 2007; 137 (01) 36-48
- 48 Théry C, Zitvogel L, Amigorena S. Exosomes: composition, biogenesis and function. Nat Rev Immunol 2002; 2 (08) 569-579
- 49 Denzer K, Kleijmeer MJ, Heijnen HF, Stoorvogel W, Geuze HJ. Exosome: from internal vesicle of the multivesicular body to intercellular signaling device. J Cell Sci 2000; 113 (Pt 19): 3365-3374
- 50 Mathivanan S, Ji H, Simpson RJ. Exosomes: extracellular organelles important in intercellular communication. J Proteomics 2010; 73 (10) 1907-1920
- 51 Properzi F, Logozzi M, Fais S. Exosomes: the future of biomarkers in medicine. Biomarkers Med 2013; 7 (05) 769-778
- 52 Keerthikumar S, Chisanga D, Ariyaratne D. , et al. ExoCarta: a web-based compendium of exosomal cargo. J Mol Biol 2016; 428 (04) 688-692
- 53 Turturici G, Tinnirello R, Sconzo G, Geraci F. Extracellular membrane vesicles as a mechanism of cell-to-cell communication: advantages and disadvantages. Am J Physiol Cell Physiol 2014; 306 (07) C621-C633
- 54 Kahner BN, Dorsam RT, Kunapuli SP. Role of P2Y receptor subtypes in platelet-derived microparticle generation. Front Biosci 2008; 13: 433-439
- 55 Principe S, Hui AB, Bruce J, Sinha A, Liu FF, Kislinger T. Tumor-derived exosomes and microvesicles in head and neck cancer: implications for tumor biology and biomarker discovery. Proteomics 2013; 13 (10-11): 1608-1623
- 56 Skog J, Würdinger T, van Rijn S. , et al. Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol 2008; 10 (12) 1470-1476
- 57 Pap E. The role of microvesicles in malignancies. Adv Exp Med Biol 2011; 714: 183-199
- 58 Erdbrügger U, Lannigan J. Analytical challenges of extracellular vesicle detection: a comparison of different techniques. Cytometry A 2016; 89 (02) 123-134
- 59 Erdbrügger U, Rudy CK, Etter ME. , et al. Imaging flow cytometry elucidates limitations of microparticle analysis by conventional flow cytometry. Cytometry A 2014; 85 (09) 756-770
- 60 van der Pol E, Coumans F, Varga Z, Krumrey M, Nieuwland R. Innovation in detection of microparticles and exosomes. J Thromb Haemost 2013; 11 (Suppl. 01) 36-45
- 61 Ayers L, Kohler M, Harrison P. , et al. Measurement of circulating cell-derived microparticles by flow cytometry: sources of variability within the assay. Thromb Res 2011; 127 (04) 370-377
- 62 Yuana Y, Bertina RM, Osanto S. Pre-analytical and analytical issues in the analysis of blood microparticles. Thromb Haemost 2011; 105 (03) 396-408
- 63 Lacroix R, Robert S, Poncelet P, Kasthuri RS, Key NS, Dignat-George F. ; ISTH SSC Workshop. Standardization of platelet-derived microparticle enumeration by flow cytometry with calibrated beads: results of the International Society on Thrombosis and Haemostasis SSC Collaborative workshop. J Thromb Haemost 2010; 8 (11) 2571-2574
- 64 Owens III AP, Mackman N. Microparticles in hemostasis and thrombosis. Circ Res 2011; 108 (10) 1284-1297
- 65 Willemze R, Bradford RL, Mooberry MJ, Roubey RA, Key NS. Plasma microparticle tissue factor activity in patients with antiphospholipid antibodies with and without clinical complications. Thromb Res 2014; 133 (02) 187-189
- 66 Khorana AA, Francis CW, Menzies KE. , et al. Plasma tissue factor may be predictive of venous thromboembolism in pancreatic cancer. J Thromb Haemost 2008; 6 (11) 1983-1985
- 67 Hisada Y, Alexander W, Kasthuri R. , et al. Measurement of microparticle tissue factor activity in clinical samples: a summary of two tissue factor-dependent FXa generation assays. Thromb Res 2016; 139: 90-97
- 68 Gao C, Xie R, Yu C. , et al. Procoagulant activity of erythrocytes and platelets through phosphatidylserine exposure and microparticles release in patients with nephrotic syndrome. Thromb Haemost 2012; 107 (04) 681-689
- 69 Lovrić Z. Definition of polytrauma: discussion on the objective definition based on quantitative estimation of multiply injured patients during wartime. Injury 2015; 46 (Suppl. 06) S24-S26
- 70 Combes V, Simon AC, Grau GE. , et al. In vitro generation of endothelial microparticles and possible prothrombotic activity in patients with lupus anticoagulant. J Clin Invest 1999; 104 (01) 93-102
- 71 Dignat-George F, Camoin-Jau L, Sabatier F. , et al. Endothelial microparticles: a potential contribution to the thrombotic complications of the antiphospholipid syndrome. Thromb Haemost 2004; 91 (04) 667-673
- 72 Pericleous C, Clarke LA, Brogan PA. , et al. Endothelial microparticle release is stimulated in vitro by purified IgG from patients with the antiphospholipid syndrome. Thromb Haemost 2013; 109 (01) 72-78
- 73 Chaturvedi S, Cockrell E, Espinola R. , et al. Circulating microparticles in patients with antiphospholipid antibodies: characterization and associations. Thromb Res 2015; 135 (01) 102-108
- 74 Zhou H, Wolberg AS, Roubey RA. Characterization of monocyte tissue factor activity induced by IgG antiphospholipid antibodies and inhibition by dilazep. Blood 2004; 104 (08) 2353-2358
- 75 Vikerfors A, Mobarrez F, Bremme K. , et al. Studies of microparticles in patients with the antiphospholipid syndrome (APS). Lupus 2012; 21 (07) 802-805
- 76 Jy W, Tiede M, Bidot CJ. , et al. Platelet activation rather than endothelial injury identifies risk of thrombosis in subjects positive for antiphospholipid antibodies. Thromb Res 2007; 121 (03) 319-325
- 77 Antwi-Baffour S, Kholia S, Aryee YK. , et al. Human plasma membrane-derived vesicles inhibit the phagocytosis of apoptotic cells--possible role in SLE. Biochem Biophys Res Commun 2010; 398 (02) 278-283
- 78 Joseph JE, Harrison P, Mackie IJ, Isenberg DA, Machin SJ. Increased circulating platelet-leucocyte complexes and platelet activation in patients with antiphospholipid syndrome, systemic lupus erythematosus and rheumatoid arthritis. Br J Haematol 2001; 115 (02) 451-459
- 79 Martínez-Zamora MA, Tàssies D, Creus M. , et al. Higher levels of procoagulant microparticles in women with recurrent miscarriage are not associated with antiphospholipid antibodies. Hum Reprod 2016; 31 (01) 46-52
- 80 Alijotas-Reig J, Palacio-Garcia C, Llurba E, Vilardell-Tarres M. Cell-derived microparticles and vascular pregnancy complications: a systematic and comprehensive review. Fertil Steril 2013; 99 (02) 441-449
- 81 Alijotas-Reig J, Palacio-Garcia C, Farran-Codina I, Ruiz-Romance M, Llurba E, Vilardell-Tarres M. Circulating cell-derived microparticles in severe preeclampsia and in fetal growth restriction. Am J Reprod Immunol 2012; 67 (02) 140-151
- 82 Bretelle F, Sabatier F, Desprez D. , et al. Circulating microparticles: a marker of procoagulant state in normal pregnancy and pregnancy complicated by preeclampsia or intrauterine growth restriction. Thromb Haemost 2003; 89 (03) 486-492
- 83 Bucciarelli P, Martinelli I, Artoni A. , et al. Circulating microparticles and risk of venous thromboembolism. Thromb Res 2012; 129 (05) 591-597
- 84 Leroyer AS, Anfosso F, Lacroix R. , et al. Endothelial-derived microparticles: biological conveyors at the crossroad of inflammation, thrombosis and angiogenesis. Thromb Haemost 2010; 104 (03) 456-463
- 85 Fourcade O, Simon MF, Viodé C. , et al. Secretory phospholipase A2 generates the novel lipid mediator lysophosphatidic acid in membrane microvesicles shed from activated cells. Cell 1995; 80 (06) 919-927
- 86 Haserück N, Erl W, Pandey D. , et al. The plaque lipid lysophosphatidic acid stimulates platelet activation and platelet-monocyte aggregate formation in whole blood: involvement of P2Y1 and P2Y12 receptors. Blood 2004; 103 (07) 2585-2592
- 87 Siess W, Zangl KJ, Essler M. , et al. Lysophosphatidic acid mediates the rapid activation of platelets and endothelial cells by mildly oxidized low density lipoprotein and accumulates in human atherosclerotic lesions. Proc Natl Acad Sci U S A 1999; 96 (12) 6931-6936
- 88 Thomas GM, Brill A, Mezouar S. , et al. Tissue factor expressed by circulating cancer cell-derived microparticles drastically increases the incidence of deep vein thrombosis in mice. J Thromb Haemost 2015; 13 (07) 1310-1319
- 89 Key NS. Analysis of tissue factor positive microparticles. Thromb Res 2010; 125 (Suppl. 01) S42-S45
- 90 van Es N, Bleker S, Sturk A, Nieuwland R. Clinical significance of tissue factor-exposing microparticles in arterial and venous thrombosis. Semin Thromb Hemost 2015; 41 (07) 718-727
- 91 Zwicker JI, Liebman HA, Neuberg D. , et al. Tumor-derived tissue factor-bearing microparticles are associated with venous thromboembolic events in malignancy. Clin Cancer Res 2009; 15 (22) 6830-6840
- 92 Bharthuar A, Khorana AA, Hutson A. , et al. Circulating microparticle tissue factor, thromboembolism and survival in pancreaticobiliary cancers. Thromb Res 2013; 132 (02) 180-184
- 93 Sabatier F, Roux V, Anfosso F, Camoin L, Sampol J, Dignat-George F. Interaction of endothelial microparticles with monocytic cells in vitro induces tissue factor-dependent procoagulant activity. Blood 2002; 99 (11) 3962-3970
- 94 Van Der Meijden PE, Van Schilfgaarde M, Van Oerle R, Renné T, ten Cate H, Spronk HM. Platelet- and erythrocyte-derived microparticles trigger thrombin generation via factor XIIa. J Thromb Haemost 2012; 10 (07) 1355-1362
- 95 Pisetsky DS, Lipsky PE. Microparticles as autoadjuvants in the pathogenesis of SLE. Nat Rev Rheumatol 2010; 6 (06) 368-372
- 96 Ullal AJ, Reich III CF, Clowse M. , et al. Microparticles as antigenic targets of antibodies to DNA and nucleosomes in systemic lupus erythematosus. J Autoimmun 2011; 36 (3-4): 173-180
- 97 Montecalvo A, Shufesky WJ, Stolz DB. , et al. Exosomes as a short-range mechanism to spread alloantigen between dendritic cells during T cell allorecognition. J Immunol 2008; 180 (05) 3081-3090
- 98 Morelli AE, Larregina AT, Shufesky WJ. , et al. Endocytosis, intracellular sorting, and processing of exosomes by dendritic cells. Blood 2004; 104 (10) 3257-3266
- 99 MacKenzie A, Wilson HL, Kiss-Toth E, Dower SK, North RA, Surprenant A. Rapid secretion of interleukin-1beta by microvesicle shedding. Immunity 2001; 15 (05) 825-835
- 100 Brodsky SV, Zhang F, Nasjletti A, Goligorsky MS. Endothelium-derived microparticles impair endothelial function in vitro. Am J Physiol Heart Circ Physiol 2004; 286 (05) H1910-H1915
- 101 Aksu K, Donmez A, Keser G. Inflammation-induced thrombosis: mechanisms, disease associations and management. Curr Pharm Des 2012; 18 (11) 1478-1493
- 102 Siljander P, Carpen O, Lassila R. Platelet-derived microparticles associate with fibrin during thrombosis. Blood 1996; 87 (11) 4651-4663
- 103 Raturi A, Miersch S, Hudson JW, Mutus B. Platelet microparticle-associated protein disulfide isomerase promotes platelet aggregation and inactivates insulin. Biochim Biophys Acta 2008; 1778 (12) 2790-2796
- 104 Reinhardt C, von Brühl ML, Manukyan D. , et al. Protein disulfide isomerase acts as an injury response signal that enhances fibrin generation via tissue factor activation. J Clin Invest 2008; 118 (03) 1110-1122
- 105 Mause SF, Weber C. Microparticles: protagonists of a novel communication network for intercellular information exchange. Circ Res 2010; 107 (09) 1047-1057
- 106 Loyer X, Vion AC, Tedgui A, Boulanger CM. Microvesicles as cell-cell messengers in cardiovascular diseases. Circ Res 2014; 114 (02) 345-353
- 107 Barry OP, Kazanietz MG, Praticò D, FitzGerald GA. Arachidonic acid in platelet microparticles up-regulates cyclooxygenase-2-dependent prostaglandin formation via a protein kinase C/mitogen-activated protein kinase-dependent pathway. J Biol Chem 1999; 274 (11) 7545-7556
- 108 Lakkaraju A, Rodriguez-Boulan E. Itinerant exosomes: emerging roles in cell and tissue polarity. Trends Cell Biol 2008; 18 (05) 199-209
- 109 van Niel G, Porto-Carreiro I, Simoes S, Raposo G. Exosomes: a common pathway for a specialized function. J Biochem 2006; 140 (01) 13-21
- 110 Pitt JM, Kroemer G, Zitvogel L. Extracellular vesicles: masters of intercellular communication and potential clinical interventions. J Clin Invest 2016; 126 (04) 1139-1143
- 111 Boon RA, Vickers KC. Intercellular transport of microRNAs. Arterioscler Thromb Vasc Biol 2013; 33 (02) 186-192
- 112 Laffont B, Corduan A, Rousseau M. , et al. Platelet microparticles reprogram macrophage gene expression and function. Thromb Haemost 2016; 115 (02) 311-323
- 113 Laffont B, Corduan A, Plé H. , et al. Activated platelets can deliver mRNA regulatory Ago2•microRNA complexes to endothelial cells via microparticles. Blood 2013; 122 (02) 253-261
- 114 Valadi H, Ekström K, Bossios A, Sjöstrand M, Lee JJ, Lötvall JO. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 2007; 9 (06) 654-659
- 115 EL Andaloussi S, Mäger I, Breakefield XO, Wood MJ. ; S ELA. Extracellular vesicles: biology and emerging therapeutic opportunities. Nat Rev Drug Discov 2013; 12 (05) 347-357