Endothelial-derived microparticles: Biological conveyors at the crossroad of inflammation, thrombosis and angiogenesis

Summary

Endothelial microparticles (EMP) are complex vesicular structures that can be shed by activated or apoptotic endothelial cells. EMP are composed of a phospholipid bilayer that exposes transmembrane proteins and receptors and encloses cytosolic components such as enzymes, transcription factors and mRNA derived from their parent cells. Thus, EMP behave as biological conveyors playing a key role in the tuning of vascular homeostasis. This review focuses on the multifaceted roles of EMP, notably in coagulation, inflammation and angiogenesis and also on the mechanisms that trigger their formation. In this context, EMP could compromise vascular homeostasis and then represent key players in the pathogenesis of several inflammatory and thrombotic diseases. Consequently, elucidating their role and their mechanisms of formation will bring new insights into the understanding of endothelial-associated diseases. Moreover, in the future, it can open novel therapeutic perspectives based on the inhibition of EMP release.

Keywords

Microparticles - endothelium - coagulation - inflammation - thrombosis - vascular homeostasis - vesiculation

• References

• 1 Wolf P. The nature and significance of platelet products in human plasma. Br J Haematol 1967; 13: 269-288.
• 2 Daleke DL. Regulation of transbilayer plasma membrane phospholipid asymmetry. J Lipid Res 2003; 44: 233-242.
• 3 Hamon Y, Broccardo C, Chambenoit O. et al. ABC1 promotes engulfment of apoptotic cells and transbilayer redistribution of phosphatidylserine. Nat Cell Biol 2000; 2: 399-406.
• 4 Zwaal RF, Schroit AJ. Pathophysiologic implications of membrane phospholipid asymmetry in blood cells. Blood 1997; 89: 1121-1132.
• 5 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: 93-102.
• 6 Szotowski B, Antoniak S, Goldin-Lang P. et al. Antioxidative treatment inhibits the release of thrombogenic tissue factor from irradiation- and cytokine-induced endothelial cells. Cardiovasc Res 2007; 73: 806-812.
• 7 Brodsky SV, Malinowski K, Golightly M. et al. Plasminogen activator inhibitor-1 promotes formation of endothelial microparticles with procoagulant potential. Circulation 2002; 106: 2372-2378.
• 8 Sapet C, Simoncini S, Loriod B. et al. Thrombin-induced endothelial microparticle generation: identification of a novel pathway involving ROCK-II activation by caspase-2. Blood 2006; 108: 1868-1876.
• 9 Simak J, Holada K, Vostal JG. Release of annexin V-binding membrane microparticles from cultured human umbilical vein endothelial cells after treatment with camptothecin. BMC Cell Biol 2002; 3: 11.
• 10 Wang JM, Wang Y, Huang JY. et al. C-Reactive protein-induced endothelial micro-particle generation in HUVECs is related to BH4-dependent NO formation. J Vasc Res 2007; 44: 241-248.
• 11 Faure V, Dou L, Sabatier F. et al. Elevation of circulating endothelial microparticles in patients with chronic renal failure. J Thromb Haemost 2006; 4: 566-573.
• 12 Boulanger CM, Amabile N, Guerin AP. et al. In vivo shear stress determines circulating levels of endothelial microparticles in end-stage renal disease. Hypertension 2007; 49: 902-908.
• 13 Simoncini S, Njock MS, Robert S. et al. TRAIL/Apo2L mediates the release of procoagulant endothelial microparticles induced by thrombin in vitro: a potential mechanism linking inflammation and coagulation. Circ Res 2009; 104: 943-951.
• 14 Curtis AM, Wilkinson PF, Gui M. et al. p38 mitogen-activated protein kinase targets the production of proinflammatory endothelial microparticles. J Thromb Haemost 2009; 7: 701-709.
• 15 Coleman ML, Sahai EA, Yeo M. et al. Membrane blebbing during apoptosis results from caspase-mediated activation of ROCK I. Nat Cell Biol 2001; 3: 339-345.
• 16 Sebbagh M, Renvoize C, Hamelin J. et al. Caspase-3-mediated cleavage of ROCK I induces MLC phosphorylation and apoptotic membrane blebbing. Nat Cell Biol 2001; 3: 346-352.
• 17 Abid Hussein MN, Nieuwland R, Hau CM. et al. Cell-derived microparticles contain caspase 3 in vitro and in vivo. J Thromb Haemost 2005; 3: 888-896.
• 18 Holdenrieder S, Stieber P, Bodenmuller H. et al. Circulating nucleosomes in serum. Ann NY Acad Sci 2001; 945: 93-102.
• 19 Abid Hussein MN, Meesters EW, Osmanovic N. et al. Antigenic characterization of endothelial cell-derived microparticles and their detection ex vivo. J Thromb Haemost 2003; 1: 2434-2443.
• 20 Garcia S, Chirinos J, Jimenez J. et al. Phenotypic assessment of endothelial micro-particles in patients with heart failure and after heart transplantation: switch from cell activation to apoptosis. J Heart Lung Transplant 2005; 24: 2184-2189.
• 21 Jimenez JJ, Jy W, Mauro LM. et al. Endothelial cells release phenotypically and quantitatively distinct microparticles in activation and apoptosis. Thromb Res 2003; 109: 175-180.
• 22 Miguet L, Pacaud K, Felden C. et al. Proteomic analysis of malignant lymphocyte membrane microparticles using double ionization coverage optimization. Proteomics 2006; 6: 153-171.
• 23 Banfi C, Brioschi M, Wait R. et al. Proteome of endothelial cell-derived procoagulant microparticles. Proteomics 2005; 5: 4443-4455.
• 24 Kushak RI, Nestoridi E, Lambert J. et al. Detached endothelial cells and microparticles as sources of tissue factor activity. Thromb Res 2005; 116: 409-419.
• 25 Perez-Casal M, Downey C, Cutillas-Moreno B. et al. Microparticle-associated endothelial protein C receptor and the induction of cytoprotective and anti-inflammatory effects. Haematologica 2009; 94: 387-394.
• 26 Perez-Casal M, Downey C, Fukudome K. et al. Activated protein C induces the release of microparticle-associated endothelial protein C receptor. Blood 2005; 105: 1515-1522.
• 27 Shet AS, Aras O, Gupta K. et al. Sickle blood contains tissue factor-positive micro-particles derived from endothelial cells and monocytes. Blood 2003; 102: 2678-2683.
• 28 Taraboletti G, D’Ascenzo S, Borsotti P. et al. Shedding of the matrix metalloproteinases MMP-2, MMP-9, and MT1-MMP as membrane vesicle-associated components by endothelial cells. Am J Pathol 2002; 160: 673-680.
• 29 Leroyer AS, Ebrahimian TG, Cochain C. et al. Microparticles from ischemic muscle promotes postnatal vasculogenesis. Circulation 2009; 119: 2808-2817.
• 30 Lacroix R, Sabatier F, Mialhe A. et al. Activation of plasminogen into plasmin at the surface of endothelial microparticles: a mechanism that modulates angiogenic properties of endothelial progenitor cells in vitro. Blood 2007; 110: 2432-2439.
• 31 Sabatier F, Roux V, Anfosso F. et al. Interaction of endothelial microparticles with monocytic cells in vitro induces tissue factor-dependent procoagulant activity. Blood 2002; 99: 3962-3970.
• 32 Agouni A, Mostefai HA, Porro C. et al. Sonic hedgehog carried by microparticles corrects endothelial injury through nitric oxide release. Faseb J 2007; 21: 2735-2741.
• 33 Biro E, Nieuwland R, Tak PP. et al. Activated complement components and complement activator molecules on the surface of cell-derived microparticles in patients with rheumatoid arthritis and healthy individuals. Ann Rheum Dis 2007; 66: 1085-1092.
• 34 Mayr M, Grainger D, Mayr U. et al. Proteomics, metabolomics, and immunomics on microparticles derived from human atherosclerotic plaques. Circ Cardiovasc Genet 2009; 2: 379-388.
• 35 Smalley DM, Root KE, Cho H. et al. Proteomic discovery of 21 proteins expressed in human plasma-derived but not platelet-derived microparticles. Thromb Haemost 2007; 97: 67-80.
• 36 Chen TS, Lai RC, Lee MM. et al. Mesenchymal stem cell secretes microparticles enriched in pre-microRNAs. Nucleic Acids Res 2010; 38: 215-224.
• 37 Deregibus MC, Cantaluppi V, Calogero R. et al. Endothelial progenitor cell derived microvesicles activate an angiogenic program in endothelial cells by a horizontal transfer of mRNA. Blood 2007; 110: 2440-2448.
• 38 Hunter MP, Ismail N, Zhang X. et al. Detection of microRNA expression in human peripheral blood microvesicles. PLoS One 2008; 3: e3694.
• 39 Koh W, Sheng CT, Tan B. et al. Analysis of deep sequencing microRNA expression profile from human embryonic stem cells derived mesenchymal stem cells reveals possible role of let-7 microRNA family in downstream targeting of hepatic nuclear factor 4 alpha. BMC Genomics 2010; 11 (Suppl. 01) S6.
• 40 Ratajczak J, Miekus K, Kucia M. et al. Embryonic stem cell-derived microvesicles reprogram hematopoietic progenitors: evidence for horizontal transfer of mRNA and protein delivery. Leukemia 2006; 20: 847-856.
• 41 Yuan A, Farber EL, Rapoport AL. et al. Transfer of microRNAs by embryonic stem cell microvesicles. PLoS One 2009; 4: e4722.
• 42 Abid Hussein MN, Boing AN, Biro E. et al. Phospholipid composition of in vitro endothelial microparticles and their in vivo thrombogenic properties. Thromb Res 2008; 121: 865-871.
• 43 Aras O, Shet A, Bach RR. et al. Induction of microparticle- and cell-associated intravascular tissue factor in human endotoxemia. Blood 2004; 103: 4545-4553.
• 44 Leroyer AS, Isobe H, Leseche G. et al. Cellular origins and thrombogenic activity of microparticles isolated from human atherosclerotic plaques. J Am Coll Cardiol 2007; 49: 772-777.
• 45 Mallat Z, Hugel B, Ohan J. et al. Shed membrane microparticles with procoagulant potential in human atherosclerotic plaques: a role for apoptosis in plaque thrombogenicity. Circulation 1999; 99: 348-353.
• 46 Mallat Z, Benamer H, Hugel B. et al. Elevated levels of shed membrane microparticles with procoagulant potential in the peripheral circulating blood of patients with acute coronary syndromes. Circulation 2000; 101: 841-843.
• 47 Del Conde I, Shrimpton CN, Thiagarajan P. et al. Tissue-factor-bearing microvesicles arise from lipid rafts and fuse with activated platelets to initiate coagulation. Blood 2005; 106: 1604-1611.
• 48 Mezentsev A, Merks RM, O’Riordan E. et al. Endothelial microparticles affect angiogenesis in vitro: role of oxidative stress. Am J Physiol Heart Circ Physiol 2005; 289: H1106-H1114.
• 49 Chahed S, Leroyer AS, Benzerroug M. et al. Increased vitreous shedding of micro-particles in proliferative diabetic retinopathy stimulates endothelial proliferation. Diabetes 2010; 59: 694-701.
• 50 Leroyer AS, Rautou PE, Silvestre JS. et al. CD40 ligand+ microparticles from human atherosclerotic plaques stimulate endothelial proliferation and angiogenesis a potential mechanism for intraplaque neovascularization. J Am Coll Cardiol 2008; 52: 1302-1311.
• 51 Amabile N, Guerin AP, Leroyer A. et al. Circulating endothelial microparticles are associated with vascular dysfunction in patients with end-stage renal failure. J Am Soc Nephrol 2005; 16: 3381-3388.
• 52 Boulanger CM, Scoazec A, Ebrahimian T. et al. Circulating microparticles from patients with myocardial infarction cause endothelial dysfunction. Circulation 2001; 104: 2649-2652.
• 53 VanWijk MJ, Nieuwland R, Boer K. et al. Microparticle subpopulations are increased in preeclampsia: possible involvement in vascular dysfunction?. Am J Obstet Gynecol. 2002; 187: 450-456.
• 54 Abid Hussein MN, Boing AN, Sturk A. et al. Inhibition of microparticle release triggers endothelial cell apoptosis and detachment. Thromb Haemost 2007; 98: 1096-1107.
• 55 Diamant M, Tushuizen ME, Abid-Hussein MN. et al. Simvastatin-induced endothelial cell detachment and microparticle release are prenylation dependent. Thromb Haemost 2008; 100: 489-497.
• 56 Nomura S. Statin and endothelial cell-derived microparticles. Thromb Haemost 2008; 100: 377-378.
• 57 Tramontano AF, O’Leary J, Black AD. et al. Statin decreases endothelial microparticle release from human coronary artery endothelial cells: implication for the Rho-kinase pathway. Biochem Biophys Res Commun 2004; 320: 34-38.
• 58 Majka M, Kijowski J, Lesko E. et al. Evidence that platelet-derived microvesicles may transfer platelet-specific immunoreactive antigens to the surface of endothelial cells and CD34+ hematopoietic stem/ progenitor cells--implication for the pathogenesis of immune thrombocytopenias. Folia Histochem Cytobiol 2007; 45: 27-32.
• 59 Mause SF, von Hundelshausen P, Zernecke A. et al. Platelet microparticles: a trans-cellular delivery system for RANTES promoting monocyte recruitment on endothelium. Arterioscler Thromb Vasc Biol 2005; 25: 1512-1518.
• 60 Kirsch T, Woywodt A, Beese M. et al. Engulfment of apoptotic cells by microvascular endothelial cells induces proinflammatory responses. Blood 2007; 109: 2854-2862.
• 61 Aliotta JM, Pereira M, Johnson KW. et al. Microvesicle entry into marrow cells mediates tissue-specific changes in mRNA by direct delivery of mRNA and induction of transcription. Exp Hematol 2010; 38: 233-245.
• 62 Zernecke A, Bidzhekov K, Noels H. et al. Delivery of microRNA-126 by apoptotic bodies induces CXCL12-dependent vascular protection. Sci Signal 2009; 2: ra81.
• 63 Bulut D, Tuns H, Mugge A. CD31+/Annexin V+ microparticles in healthy off-springs of patients with coronary artery disease. Eur J Clin Invest 2009; 39: 17-22.
• 64 Nozaki T, Sugiyama S, Koga H. et al. Significance of a multiple biomarkers strategy including endothelial dysfunction to improve risk stratification for cardiovascular events in patients at high risk for coronary heart disease. J Am Coll Cardiol 2009; 54: 601-608.
• 65 Jung KH, Chu K, Lee ST. et al. Circulating endothelial microparticles as a marker of cerebrovascular disease. Ann Neurol 2009; 66: 191-199.
• 66 Simak J, Gelderman MP, Yu H. et al. Circulating endothelial microparticles in acute ischemic stroke: a link to severity, lesion volume and outcome. J Thromb Haemost 2006; 4: 1296-1302.
• 67 Bernard S, Loffroy R, Serusclat A. et al. Increased levels of endothelial microparticles CD144 (VE-Cadherin) positives in type 2 diabetic patients with coronary noncalcified plaques evaluated by multidetector computed tomography (MDCT). Atherosclerosis 2009; 203: 429-435.
• 68 Feng B, Chen Y, Luo Y. et al. Circulating level of microparticles and their correlation with arterial elasticity and endothelium-dependent dilation in patients with type 2 diabetes mellitus. Atherosclerosis 2010; 208: 264-269.
• 69 Koga H, Sugiyama S, Kugiyama K. et al. Elevated levels of VE-cadherin-positive endothelial microparticles in patients with type 2 diabetes mellitus and coronary artery disease. J Am Coll Cardiol 2005; 45: 1622-1630.
• 70 Nomura S. Dynamic role of microparticles in type 2 diabetes mellitus. Curr Diabetes Rev 2009; 5: 245-251.
• 71 Agouni A, Lagrue-Lak-Hal AH, Ducluzeau PH. et al. Endothelial dysfunction caused by circulating microparticles from patients with metabolic syndrome. Am J Pathol 2008; 173: 1210-1219.
• 72 Amabile N, Heiss C, Chang V. et al. Increased CD62e(+) endothelial microparticle levels predict poor outcome in pulmonary hypertension patients. J Heart Lung Transplant 2009; 28: 1081-1086.
• 73 Preston RA, Jy W, Jimenez JJ. et al. Effects of severe hypertension on endothelial and platelet microparticles. Hypertension 2003; 41: 211-217.
• 74 Wang JM, Su C, Wang Y. et al. Elevated circulating endothelial microparticles and brachial-ankle pulse wave velocity in well-controlled hypertensive patients. J Hum Hypertens 2009; 23: 307-315.
• 75 Jimenez JJ, Jy W, Mauro LM. et al. Endothelial microparticles released in thrombotic thrombocytopenic purpura express von Willebrand factor and markers of endothelial activation. Br J Haematol 2003; 123: 896-902.
• 76 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: 667-673.
• 77 Pericleous C, Giles I, Rahman A. Are endothelial microparticles potential markers of vascular dysfunction in the antiphospholipid syndrome?. Lupus 2009; 18: 671-675.
• 78 Erdbruegger U, Grossheim M, Hertel B. et al. Diagnostic role of endothelial microparticles in vasculitis. Rheumatology (Oxford) 2008; 47: 1820-1825.
• 79 Georgescu A, Alexandru N, Popov D. et al. Chronic venous insufficiency is associated with elevated level of circulating microparticles. J Thromb Haemost 2009; 7: 1566-1575.
• 80 Chirinos JA, Heresi GA, Velasquez H. et al. Elevation of endothelial microparticles, platelets, and leukocyte activation in patients with venous thromboembolism. J Am Coll Cardiol 2005; 45: 1467-1471.
• 81 Helley D, Peffault de Latour R, Porcher R. et al. Evaluation of hemostasis and endothelial function in patients with paroxysmal nocturnal hemoglobinuria receiving eculizumab. Haematologica 2010; 95: 574-581.
• 82 Gonzalez-Quintero VH, Smarkusky LP, Jimenez JJ. et al. Elevated plasma endothelial microparticles: preeclampsia versus gestational hypertension. Am J Obstet Gynecol 2004; 191: 1418-1424.
• 83 Esposito K, Ciotola M, Schisano B. et al. Endothelial microparticles correlate with endothelial dysfunction in obese women. J Clin Endocrinol Metab 2006; 91: 3676-3679.
• 84 Minagar A, Jy W, Jimenez JJ. et al. Elevated plasma endothelial microparticles in multiple sclerosis. Neurology. 2001; 56: 1319-1324.
• 85 Morel O, Hugel B, Jesel L. et al. Sustained elevated amounts of circulating procoagulant membrane microparticles and soluble GPV after acute myocardial infarction in diabetes mellitus. Thromb Haemost 2004; 91: 345-353.
• 86 Sabatier F, Camoin-Jau L, Anfosso F. et al. Circulating endothelial cells, microparticles and progenitors: key players towards the definition of vascular competence. J Cell Mol Med 2009; 13: 454-471.
• 87 Morel O, Toti F, Hugel B. et al. Procoagulant microparticles: disrupting the vascular homeostasis equation?. Arterioscler Thromb Vasc Biol 2006; 26: 2594-2604.
• 88 Duval A, Helley D, Capron L. et al. Endothelial dysfunction in systemic lupus patients with low disease activity: evaluation by quantification and characterization of circulating endothelial microparticles, role of anti-endothelial cell antibodies. Rheumatology (Oxford) 2010; 49: 1049-1055.
• 89 van Ierssel SH, Van Craenenbroeck EM, Conraads VM. et al. Flow cytometric detection of endothelial microparticles (EMP): Effects of centrifugation and storage alter with the phenotype studied. Thromb Res 2010; 125: 332-339.
• 90 Boulanger CM, Leroyer AS, Amabile N. et al. Circulating endothelial microparticles: a new marker of vascular injury. Ann Cardiol Angeiol (Paris) 2008; 57: 149-154.
• 91 Nomura S, Inami N, Kimura Y. et al. Effect of nifedipine on adiponectin in hypertensive patients with type 2 diabetes mellitus. J Hum Hypertens 2007; 21: 38-44.
• 92 Nomura S, Shouzu A, Omoto S. et al. Benidipine improves oxidized LDL-dependent monocyte and endothelial dysfunction in hypertensive patients with type 2 diabetes mellitus. J Hum Hypertens 2005; 19: 551-557.
• 93 Nomura S, Shouzu A, Omoto S. et al. Effects of eicosapentaenoic acid on endothelial cell-derived microparticles, angiopoietins and adiponectin in patients with type 2 diabetes. J Atheroscler Thromb 2009; 16: 83-90.
• 94 Esposito K, Ciotola M, Giugliano D. Pioglitazone reduces endothelial microparticles in the metabolic syndrome. Arterioscler Thromb Vasc Biol 2006; 26: 1926.