Semin Thromb Hemost 2009; 35(5): 488-496
DOI: 10.1055/s-0029-1234144
© Thieme Medical Publishers

Microparticles and Arterial Disease

Andrew Blann1 , Eduard Shantsila1 , Alena Shantsila1
  • 1Haemostasis, Thrombosis and Vascular Biology Unit, University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham, United Kingdom
Further Information

Publication History

Publication Date:
08 September 2009 (online)

ABSTRACT

Microparticles (MPs) are small (diameter <1 μm) fragments that seem likely to represent some form of physiology and/or pathophysiology of the originating cell, be it endothelial, platelet, or leukocyte. Increased numbers of MPs are found in various disease states, including cardiovascular disease, and a considerable weight of literature suggests a value in dissecting the various aspects of cell biology. A role in coagulation has been proposed because there is evidence that some MPs expose tissue factor. This article reviews the definitions, mechanisms of production, and links with pathophysiology of MPs in arterial disease, and thus whether or not they can contribute to improved patient care.

REFERENCES

  • 1 Davì G, Patrono C. Platelet activation and atherothrombosis.  N Engl J Med. 2007;  357(24) 2482-2494
  • 2 Blann A D, Lip G Y. Virchow’s triad revisited: the importance of soluble coagulation factors, the endothelium, and platelets.  Thromb Res. 2001;  101(4) 321-327
  • 3 Libby P. Inflammation in atherosclerosis.  Nature. 2002;  420(6917) 868-874
  • 4 Abrams C S, Ellison N, Budzynski A Z, Shattil S J. Direct detection of activated platelets and platelet-derived microparticles in humans.  Blood. 1990;  75(1) 128-138
  • 5 Scharf R E, Tomer A, Marzec U M, Teirstein P S, Ruggeri Z M, Harker L A. Activation of platelets in blood perfusing angioplasty-damaged coronary arteries. Flow cytometric detection.  Arterioscler Thromb. 1992;  12(12) 1475-1487
  • 6 Dachary-Prigent J, Freyssinet J M, Pasquet J M, Carron J C, Nurden A T. Annexin V as a probe of aminophospholipid exposure and platelet membrane vesiculation: a flow cytometry study showing a role for free sulfhydryl groups.  Blood. 1993;  81(10) 2554-2565
  • 7 Satta N, Toti F, Feugeas O et al.. Monocyte vesiculation is a possible mechanism for dissemination of membrane-associated procoagulant activities and adhesion molecules after stimulation by lipopolysaccharide.  J Immunol. 1994;  153(7) 3245-3255
  • 8 Mallat Z, Hugel B, Ohan J, Lesèche G, Freyssinet J M, Tedgui A. Shed membrane microparticles with procoagulant potential in human atherosclerotic plaques: a role for apoptosis in plaque thrombogenicity.  Circulation. 1999;  99(3) 348-353
  • 9 Combes V, Simon A C, Grau G E et al.. In vitro generation of endothelial microparticles and possible prothrombotic activity in patients with lupus anticoagulant.  J Clin Invest. 1999;  104(1) 93-102
  • 10 ISTH Scientific Subcommittee Minutes .Papers presented at: 54th Annual Scientific and Standardization Committee Meeting; July 2–5, 2008; Vienna, Austria; and 55th Annual Scientific and Standardization Committee Meeting July 6–11, 2009 Boston, MA; Available at: http://www.med.unc.edu/isth/ssc/04sscminutes/04wg_vascular_biology.html
  • 11 Perez-Pujol S, Marker P H, Key N S. Platelet microparticles are heterogeneous and highly dependent on the activation mechanism: studies using a new digital flow cytometer.  Cytometry A. 2007;  71(1) 38-45
  • 12 Lin Y H, Lee G B. Optically induced flow cytometry for continuous microparticle counting and sorting.  Biosens Bioelectron. 2008;  24(4) 572-578
  • 13 Macey M, Azam U, McCarthy D et al.. Evaluation of the anticoagulants EDTA and citrate, theophylline, adenosine, and dipyridamole (CTAD) for assessing platelet activation on the ADVIA 120 hematology system.  Clin Chem. 2002;  48(6 Pt 1) 891-899
  • 14 Jy W, Horstman L L, Jimenez J J et al.. Measuring circulating cell-derived microparticles.  J Thromb Haemost. 2004;  2 1842-1851
  • 15 Shah M D, Bergeron A L, Dong J F, López J A. Flow cytometric measurement of microparticles: pitfalls and protocol modifications.  Platelets. 2008;  19(5) 365-372
  • 16 Jimenez J J, Jy W, Mauro L M, Soderland C, Horstman L L, Ahn Y S. Endothelial cells release phenotypically and quantitatively distinct microparticles in activation and apoptosis.  Thromb Res. 2003;  109(4) 175-180
  • 17 Banfi C, Brioschi M, Wait R et al.. Proteome of endothelial cell-derived procoagulant microparticles.  Proteomics. 2005;  5(17) 4443-4455
  • 18 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(10) 1622-1630
  • 19 Abid Hussein M N, Böing A N, Biró E et al.. Phospholipid composition of in vitro endothelial microparticles and their in vivo thrombogenic properties.  Thromb Res. 2008;  121(6) 865-871
  • 20 Flaumenhaft R, Dilks J R, Richardson J et al.. Megakaryocyte-derived microparticles: direct visualization and distinction from platelet-derived microparticles.  Blood. 2009;  113(5) 1112-1121
  • 21 George J N, Pickett E B, Saucerman S et al.. Platelet surface glycoproteins. Studies on resting and activated platelets and platelet membrane microparticles in normal subjects, and observations in patients during adult respiratory distress syndrome and cardiac surgery.  J Clin Invest. 1986;  78(2) 340-348
  • 22 Garcia B A, Smalley D M, Cho H, Shabanowitz J, Ley K, Hunt D F. The platelet microparticle proteome.  J Proteome Res. 2005;  4(5) 1516-1521
  • 23 Biró E, Akkerman J W, Hoek F J et al.. The phospholipid composition and cholesterol content of platelet-derived microparticles: a comparison with platelet membrane fractions.  J Thromb Haemost. 2005;  3(12) 2754-2763
  • 24 Morel O, Toti F, Hugel B et al.. Procoagulant microparticles: disrupting the vascular homeostasis equation?.  Arterioscler Thromb Vasc Biol. 2006;  26(12) 2594-2604
  • 25 Barry O P, Praticò D, Savani R C, FitzGerald G A. Modulation of monocyte-endothelial cell interactions by platelet microparticles.  J Clin Invest. 1998;  102(1) 136-144
  • 26 Gambim M H, do Carmo AdeO, Marti L, Veríssimo-Filho S, Lopes L R, Janiszewski M. Platelet-derived exosomes induce endothelial cell apoptosis through peroxynitrite generation: experimental evidence for a novel mechanism of septic vascular dysfunction.  Crit Care. 2007;  11(5) R107
  • 27 Jy W, Mao W W, Horstman L, Tao J, Ahn Y S. Platelet microparticles bind, activate and aggregate neutrophils in vitro.  Blood Cells Mol Dis. 1995;  21(3) 217-231, discussion 231a
  • 28 Gasser O, Hess C, Miot S, Deon C, Sanchez J C, Schifferli J A. Characterisation and properties of ectosomes released by human polymorphonuclear neutrophils.  Exp Cell Res. 2003;  285(2) 243-257
  • 29 Mesri M, Altieri D C. Endothelial cell activation by leukocyte microparticles.  J Immunol. 1998;  161(8) 4382-4387
  • 30 Pluskota E, Woody N M, Szpak D et al.. Expression, activation, and function of integrin alphaMbeta2 (Mac-1) on neutrophil-derived microparticles.  Blood. 2008;  112(6) 2327-2335
  • 31 Scanu A, Molnarfi N, Brandt K J, Gruaz L, Dayer J M, Burger D. Stimulated T cells generate microparticles, which mimic cellular contact activation of human monocytes: differential regulation of pro- and anti-inflammatory cytokine production by high-density lipoproteins.  J Leukoc Biol. 2008;  83(4) 921-927
  • 32 Berckmans R J, Neiuwland R, Böing A N, Romijn F P, Hack C E, Sturk A. Cell-derived microparticles circulate in healthy humans and support low grade thrombin generation.  Thromb Haemost. 2001;  85(4) 639-646
  • 33 Ueba T, Haze T, Sugiyama M et al.. Level, distribution and correlates of platelet-derived microparticles in healthy individuals with special reference to the metabolic syndrome.  Thromb Haemost. 2008;  100(2) 280-285
  • 34 Wang J M, Huang Y J, Wang Y et al.. Increased circulating CD31+/CD42-microparticles are associated with impaired systemic artery elasticity in healthy subjects.  Am J Hypertens. 2007;  20(9) 957-964
  • 35 van der Zee P M, Biró E, Ko Y et al.. P-selectin- and CD63-exposing platelet microparticles reflect platelet activation in peripheral arterial disease and myocardial infarction.  Clin Chem. 2006;  52(4) 657-664
  • 36 Michelson A D, Rajasekhar D, Bednarek F J, Barnard M R. Platelet and platelet-derived microparticle surface factor V/Va binding in whole blood: differences between neonates and adults.  Thromb Haemost. 2000;  84(4) 689-694
  • 37 Nomura S, Miyazaki Y, Miyake T et al.. Detection of platelet-derived microparticles in patients with diabetes.  Am J Hematol. 1993;  44(3) 213
  • 38 Nomura S, Suzuki M, Katsura K et al.. Platelet-derived microparticles may influence the development of atherosclerosis in diabetes mellitus.  Atherosclerosis. 1995;  116(2) 235-240
  • 39 Tan K T, Tayebjee M H, Lim H S, Lip G Y. Clinically apparent atherosclerotic disease in diabetes is associated with an increase in platelet microparticle levels.  Diabet Med. 2005;  22(12) 1657-1662
  • 40 Ogata N, Imaizumi M, Nomura S et al.. Increased levels of platelet-derived microparticles in patients with diabetic retinopathy.  Diabetes Res Clin Pract. 2005;  68(3) 193-201
  • 41 Koga H, Sugiyama S, Kugiyama K et al.. Elevated levels of remnant lipoproteins are associated with plasma platelet microparticles in patients with type-2 diabetes mellitus without obstructive coronary artery disease.  Eur Heart J. 2006;  27(7) 817-823
  • 42 Bernard S, Loffroy R, Sérusclat 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(2) 429-435
  • 43 Ogata N, Nomura S, Shouzu A, Imaizumi M, Arichi M, Matsumura M. Elevation of monocyte-derived microparticles in patients with diabetic retinopathy.  Diabetes Res Clin Pract. 2006;  73(3) 241-248
  • 44 Sabatier F, Darmon P, Hugel B et al.. Type 1 and type 2 diabetic patients display different patterns of cellular microparticles.  Diabetes. 2002;  51(9) 2840-2845
  • 45 Preston R A, Jy W, Jimenez J J et al.. Effects of severe hypertension on endothelial and platelet microparticles.  Hypertension. 2003;  41(2) 211-217
  • 46 Wang J M, 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(5) 307-315
  • 47 Bakouboula B, Morel O, Faure A et al.. Procoagulant membrane microparticles correlate with the severity of pulmonary arterial hypertension.  Am J Respir Crit Care Med. 2008;  177(5) 536-543
  • 48 Amabile N, Heiss C, Real W M et al.. Circulating endothelial microparticle levels predict hemodynamic severity of pulmonary hypertension.  Am J Respir Crit Care Med. 2008;  177(11) 1268-1275
  • 49 Casey R G, Joyce M, Roche-Nagle G, Cox D, Bouchier-Hayes D J. Young male smokers have altered platelets and endothelium that precedes atherosclerosis.  J Surg Res. 2004;  116(2) 227-233
  • 50 Goichot B, Grunebaum L, Desprez D et al.. Circulating procoagulant microparticles in obesity.  Diabetes Metab. 2006;  32(1) 82-85
  • 51 Esposito K, Ciotola M, Schisano B et al.. Endothelial microparticles correlate with endothelial dysfunction in obese women.  J Clin Endocrinol Metab. 2006;  91(9) 3676-3679
  • 52 Bulut D, Maier K, Bulut-Streich N, Börgel J, Hanefeld C, Mügge A. Circulating endothelial microparticles correlate inversely with endothelial function in patients with ischemic left ventricular dysfunction.  J Card Fail. 2008;  14(4) 336-340
  • 53 Werner N, Wassmann S, Ahlers P, Kosiol S, Nickenig G. Circulating CD31+/annexin V+ apoptotic microparticles correlate with coronary endothelial function in patients with coronary artery disease.  Arterioscler Thromb Vasc Biol. 2006;  26(1) 112-116
  • 54 Héloire F, Weill B, Weber S, Batteux F. Aggregates of endothelial microparticles and platelets circulate in peripheral blood. Variations during stable coronary disease and acute myocardial infarction.  Thromb Res. 2003;  110(4) 173-180
  • 55 Leroyer A S, Rautou P E, Silvestre J S 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(16) 1302-1311
  • 56 Canault M, Leroyer A S, Peiretti F et al.. Microparticles of human atherosclerotic plaques enhance the shedding of the tumor necrosis factor-alpha converting enzyme/ADAM17 substrates, tumor necrosis factor and tumor necrosis factor receptor-1.  Am J Pathol. 2007;  171(5) 1713-1723
  • 57 Craft J A, Marsh N A. Increased generation of platelet-derived microparticles following percutaneous transluminal coronary angioplasty.  Blood Coagul Fibrinolysis. 2003;  14(8) 719-728
  • 58 Bernal-Mizrachi L, Jy W, Jimenez J J et al.. High levels of circulating endothelial microparticles in patients with acute coronary syndromes.  Am Heart J. 2003;  145(6) 962-970
  • 59 Zielińska M, Koniarek W, Goch J H et al.. Circulating endothelial microparticles in patients with acute myocardial infarction.  Kardiol Pol. 2005;  62(6) 531-542, discussion 543–544
  • 60 Katopodis J N, Kolodny L, Jy W et al.. Platelet microparticles and calcium homeostasis in acute coronary ischemias.  Am J Hematol. 1997;  54(2) 95-101
  • 61 Bernal-Mizrachi L, Jy W, Fierro C et al.. Endothelial microparticles correlate with high-risk angiographic lesions in acute coronary syndromes.  Int J Cardiol. 2004;  97(3) 439-446
  • 62 Huisse M G, Lanoy E, Tcheche D et al.. Prothrombotic markers and early spontaneous recanalization in ST-segment elevation myocardial infarction.  Thromb Haemost. 2007;  98(2) 420-426
  • 63 Matsumoto N, Nomura S, Kamihata H, Kimura Y, Iwasaka T. Association of platelet-derived microparticles with C-C chemokines on vascular complication in patients with acute myocardial infarction.  Clin Appl Thromb Hemost. 2002;  8(3) 279-286
  • 64 Singh N, Gemmell C H, Daly P A, Yeo E L. Elevated platelet-derived microparticle levels during unstable angina.  Can J Cardiol. 1995;  11(11) 1015-1021
  • 65 Michelsen A E, Brodin E, Brosstad F, Hansen J B. Increased level of platelet microparticles in survivors of myocardial infarction.  Scand J Clin Lab Invest. 2008;  68(5) 386-392
  • 66 Gawaz M, Neumann F J, Ott I, Schiessler A, Schömig A. Platelet function in acute myocardial infarction treated with direct angioplasty.  Circulation. 1996;  93(2) 229-237
  • 67 Simak J, Gelderman M P, Yu H, Wright V, Baird A E. Circulating endothelial microparticles in acute ischemic stroke: a link to severity, lesion volume and outcome.  J Thromb Haemost. 2006;  4(6) 1296-1302
  • 68 Williams J B, Jauch E C, Lindsell C J, Campos B. Endothelial microparticle levels are similar in acute ischemic stroke and stroke mimics due to activation and not apoptosis/necrosis.  Acad Emerg Med. 2007;  14(8) 685-690
  • 69 Lee Y J, Jy W, Horstman L L et al.. Elevated platelet microparticles in transient ischemic attacks, lacunar infarcts, and multiinfarct dementias.  Thromb Res. 1993;  72(4) 295-304
  • 70 Geiser T, Sturzenegger M, Genewein U, Haeberli A, Beer J H. Mechanisms of cerebrovascular events as assessed by procoagulant activity, cerebral microemboli, and platelet microparticles in patients with prosthetic heart valves.  Stroke. 1998;  29(9) 1770-1777
  • 71 Zeiger F, Stephan S, Hoheisel G, Pfeiffer D, Ruehlmann C, Koksch M. P-Selectin expression, platelet aggregates, and platelet-derived microparticle formation are increased in peripheral arterial disease.  Blood Coagul Fibrinolysis. 2000;  11(8) 723-728
  • 72 Nomura S, Imamura A, Okuno M et al.. Platelet-derived microparticles in patients with arteriosclerosis obliterans: enhancement of high shear-induced microparticle generation by cytokines.  Thromb Res. 2000;  98(4) 257-268
  • 73 Lechner D, Weltermann A. Circulating tissue factor-exposing microparticles.  Thromb Res. 2008;  122(suppl 1) S47-S54
  • 74 Tans G, Rosing J, Thomassen M C, Heeb M J, Zwaal R F, Griffin J H. Comparison of anticoagulant and procoagulant activities of stimulated platelets and platelet-derived microparticles.  Blood. 1991;  77(12) 2641-2648
  • 75 Sinauridze E I, Kireev D A, Popenko N Y et al.. Platelet microparticle membranes have 50- to 100-fold higher specific procoagulant activity than activated platelets.  Thromb Haemost. 2007;  97(3) 425-434
  • 76 Ilveskero S, Siljander P, Lassila R. Procoagulant activity on platelets adhered to collagen or plasma clot.  Arterioscler Thromb Vasc Biol. 2001;  21(4) 628-635
  • 77 Siljander P, Carpen O, Lassila R. Platelet-derived microparticles associate with fibrin during thrombosis.  Blood. 1996;  87(11) 4651-4663
  • 78 Hoffman M, Monroe D M, Roberts H R. Coagulation factor IXa binding to activated platelets and platelet-derived microparticles: a flow cytometric study.  Thromb Haemost. 1992;  68(1) 74-78
  • 79 Falati S, Liu Q, Gross P et al.. Accumulation of tissue factor into developing thrombi in vivo is dependent upon microparticle P-selectin glycoprotein ligand 1 and platelet P-selectin.  J Exp Med. 2003;  197(11) 1585-1598
  • 80 Poitevin S, Cochery-Nouvellon E, Dupont A, Nguyen P. Monocyte IL-10 produced in response to lipopolysaccharide modulates thrombin generation by inhibiting tissue factor expression and release of active tissue factor-bound microparticles.  Thromb Haemost. 2007;  97(4) 598-607
  • 81 Rauch U, Bonderman D, Bohrmann B et al.. Transfer of tissue factor from leukocytes to platelets is mediated by CD15 and tissue factor.  Blood. 2000;  96(1) 170-175
  • 82 Kushak R I, Nestoridi E, Lambert J, Selig M K, Ingelfinger J R, Grabowski E F. Detached endothelial cells and microparticles as sources of tissue factor activity.  Thromb Res. 2005;  116(5) 409-419
  • 83 Jy W, Jimenez J J, Mauro L M et al.. Endothelial microparticles induce formation of platelet aggregates via a von Willebrand factor/ristocetin dependent pathway, rendering them resistant to dissociation.  J Thromb Haemost. 2005;  3(6) 1301-1308
  • 84 Brodsky S V, Malinowski K, Golightly M, Jesty J, Goligorsky M S. Plasminogen activator inhibitor-1 promotes formation of endothelial microparticles with procoagulant potential.  Circulation. 2002;  106(18) 2372-2378
  • 85 Leroyer A S, Isobe H, Lesèche G et al.. Cellular origins and thrombogenic activity of microparticles isolated from human atherosclerotic plaques.  J Am Coll Cardiol. 2007;  49(7) 772-777
  • 86 Chironi G, Simon A, Hugel B et al.. Circulating leukocyte-derived microparticles predict subclinical atherosclerosis burden in asymptomatic subjects.  Arterioscler Thromb Vasc Biol. 2006;  26(12) 2775-2780
  • 87 Namba M, Tanaka A, Shimada K et al.. Circulating platelet-derived microparticles are associated with atherothrombotic events: a marker for vulnerable blood.  Arterioscler Thromb Vasc Biol. 2007;  27(1) 255-256
  • 88 Del Turco S, Basta G, Lazzerini G et al.. Effect of the administration of n-3 polyunsaturated fatty acids on circulating levels of microparticles in patients with a previous myocardial infarction.  Haematologica. 2008;  93(6) 892-899
  • 89 Matzdorff A C, Kühnel G, Kemkes-Matthes B, Pralle H, Voss R, Fareed J. Effect of glycoprotein IIb/IIIa inhibitors on CD62p expression, platelet aggregates, and microparticles in vitro.  J Lab Clin Med. 2000;  135(3) 247-255
  • 90 Nomura S, Shouzu A, Omoto S, Nishikawa M, Fukuhara S, Iwasaka T. Effect of valsartan on monocyte/endothelial cell activation markers and adiponectin in hypertensive patients with type 2 diabetes mellitus.  Thromb Res. 2006;  117(4) 385-392
  • 91 Serebruany V L, Malinin A I, Jerome S D et al.. Effects of clopidogrel and aspirin combination versus aspirin alone on platelet aggregation and major receptor expression in patients with heart failure: the Plavix Use for Treatment Of Congestive Heart Failure (PLUTO-CHF) trial.  Am Heart J. 2003;  146 713-720
  • 92 Nomura S, Takahashi N, Inami N et al.. Probucol and ticlopidine: effect on platelet and monocyte activation markers in hyperlipidemic patients with and without type 2 diabetes.  Atherosclerosis. 2004;  174(2) 329-335
  • 93 Diamant M, Tushuizen M E, Abid-Hussein M N et al.. Simvastatin-induced endothelial cell detachment and microparticle release are prenylation dependent.  Thromb Haemost. 2008;  100(3) 489-497
  • 94 Esposito K, Ciotola M, Giugliano D. Pioglitazone reduces endothelial microparticles in the metabolic syndrome.  Arterioscler Thromb Vasc Biol. 2006;  26(8) 1926
  • 95 Pirro M, Schillaci G, Bagaglia F et al.. Microparticles derived from endothelial progenitor cells in patients at different cardiovascular risk.  Atherosclerosis. 2008;  197(2) 757-767
  • 96 Pirro M, Schillaci G, Paltriccia R et al.. Increased ratio of CD31 + /CD42- microparticles to endothelial progenitors as a novel marker of atherosclerosis in hypercholesterolemia.  Arterioscler Thromb Vasc Biol. 2006;  26(11) 2530-2535
  • 97 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(7) 2432-2439
  • 98 George F D. Microparticles in vascular diseases.  Thromb Res. 2008;  122(Suppl 1) S55-S59
  • 99 Robert S, Poncelet P, Lacroix R et al.. Standardization of platelet-derived microparticle counting using calibrated beads and a Cytomics FC500 routine flow cytometer: a first step towards multicenter studies?.  J Thromb Haemost. 2009;  7(1) 190-197
  • 100 Shet A S. Characterizing blood microparticles: technical aspects and challenges.  Vasc Health Risk Manag. 2008;  4(4) 769-774

Dr. A.D. Blann

Haemostasis, Thrombosis and Vascular Biology Unit, University of Birmingham Centre for Cardiovascular Sciences

City Hospital, Birmingham B18 7QH, UK

Email: a.blann@bham.ac.uk