The involvement of circulating microparticles in inflammation, coagulation and cardiovascular diseases.

Microparticles (MPs) are small vesicles, ranging in size from 0.1 microm to 2 microm, originating from plasma membranes of endothelial cells, platelets, leukocytes and erythrocytes. MPs can transfer antigens and receptors to cell types that are different from their cell of origin. Circulating MPs provide a procoagulant aminophospholipid surface for the assembly of the specific enzymes of coagulation. Both tissue factor and phosphatidylserine are exposed on MP outer membranes. In addition, MPs can play a significant role in vascular function and inflammation by modulating nitric oxide and prostacyclin production in endothelial cells, and stimulating cytokine release and tissue factor induction in endothelial cells, as well as monocyte chemotaxis and adherence to the endothelium. Finally, increased levels of MPs have been found in the presence of acute coronary syndromes, ischemic stroke, diabetes, systemic and pulmonary hypertension, and hypertriglyceridemia. From a practical point of view, MPs could be considered to be important markers of cardiovascular risk, as well as surrogate end points for assessing the efficacy of new drugs and therapies.

[1]  B. Lentz,et al.  Exposure of platelet membrane phosphatidylserine regulates blood coagulation. , 2003, Progress in lipid research.

[2]  J. Freyssinet,et al.  Monocyte vesiculation is a possible mechanism for dissemination of membrane-associated procoagulant activities and adhesion molecules after stimulation by lipopolysaccharide. , 1994, Journal of immunology.

[3]  R. Hebbel,et al.  Sickle blood contains tissue factor-positive microparticles derived from endothelial cells and monocytes. , 2003, Blood.

[4]  A. Shet.  Characterizing blood microparticles: Technical aspects and challenges , 2008, Vascular health and risk management.

[5]  Tomohiro Sakamoto,et al.  Elevated levels of VE-cadherin-positive endothelial microparticles in patients with type 2 diabetes mellitus and coronary artery disease. , 2005, Journal of the American College of Cardiology.

[6]  K. Usadel,et al.  Chronic selective hypertriglyceridemia impairs endothelium-dependent vasodilatation in rats. , 1999, Cardiovascular research.

[7]  G. Leftheriotis,et al.  Endothelial dysfunction caused by circulating microparticles from patients with metabolic syndrome. , 2008, The American journal of pathology.

[8]  M. Mesri,et al.  Leukocyte Microparticles Stimulate Endothelial Cell Cytokine Release and Tissue Factor Induction in a JNK1 Signaling Pathway* , 1999, The Journal of Biological Chemistry.

[9]  F. Dignat-George,et al.  Immunologic phenotype of cultured endothelial cells: quantitative analysis of cell surface molecules. , 1997, Tissue antigens.

[10]  L. Horstman,et al.  Endothelial microparticles induce formation of platelet aggregates via a von Willebrand factor/ristocetin dependent pathway, rendering them resistant to dissociation , 2005, Journal of thrombosis and haemostasis : JTH.

[11]  C. Ludlam,et al.  Plasma microparticles and vascular disorders , 2007, British journal of haematology.

[12]  P. Wolf.  The Nature and Significance of Platelet Products in Human Plasma , 1967, British journal of haematology.

[13]  Richard A. Preston,et al.  Effects of Severe Hypertension on Endothelial and Platelet Microparticles , 2003, Hypertension.

[14]  R. Nieuwland,et al.  Cellular microparticles: new players in the field of vascular disease? , 2004, European journal of clinical investigation.

[15]  D. Giugliano,et al.  Pioglitazone reduces endothelial microparticles in the metabolic syndrome. , 2006, Arteriosclerosis, thrombosis, and vascular biology.

[16]  H. Movat,et al.  The in vivo quantitation and kinetics of monocyte migration into acute inflammatory tissue. , 1981, The American journal of pathology.

[17]  T. Nakayama,et al.  Level, distribution and correlates of platelet-derived microparticles in healthy individuals with special reference to the metabolic syndrome , 2008, Thrombosis and Haemostasis.

[18]  A. Zeiher,et al.  Vitamin C Inhibits Endothelial Cell Apoptosis in Congestive Heart Failure , 2001, Circulation.

[19]  T. Iwasaka,et al.  Effect of Ticlopidine on Monocyte-derived Microparticles and Activated Platelet Markers in Diabetes Mellitus , 2004, Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis.

[20]  M. Goligorsky,et al.  Endothelium-derived microparticles impair endothelial function in vitro. , 2004, American journal of physiology. Heart and circulatory physiology.

[21]  F. Braet,et al.  Using Antibody Arrays to Detect Microparticles from Acute Coronary Syndrome Patients Based on Cluster of Differentiation (CD) Antigen Expression* , 2009, Molecular & Cellular Proteomics.

[22]  Mona D. Shah,et al.  Flow cytometric measurement of microparticles: Pitfalls and protocol modifications , 2008, Platelets.

[23]  A. Schroit,et al.  Pathophysiologic implications of membrane phospholipid asymmetry in blood cells. , 1997, Blood.

[24]  José A López,et al.  Tissue-factor-bearing microvesicles arise from lipid rafts and fuse with activated platelets to initiate coagulation. , 2005, Blood.

[25]  A. Enjeti,et al.  Detection and Measurement of Microparticles: An Evolving Research Tool for Vascular Biology , 2007, Seminars in thrombosis and hemostasis.

[26]  J. Rosing,et al.  Prothrombin activation on phospholipid membranes with positive electrostatic potential. , 1988, Biochemistry.

[27]  B. Weill,et al.  Aggregates of endothelial microparticles and platelets circulate in peripheral blood. Variations during stable coronary disease and acute myocardial infarction. , 2003, Thrombosis research.

[28]  G. Zimmerman,et al.  Novel leukocyte agonists are released by endothelial cells exposed to peroxide. , 1992, The Journal of biological chemistry.

[29]  F. Siddiqui,et al.  The presence and release of tissue factor from human platelets , 2002, Platelets.

[30]  Toshiji Iwasaka,et al.  Effects of Losartan and Simvastatin on Monocyte-Derived Microparticles in Hypertensive Patients With and Without Type 2 Diabetes Mellitus , 2004, Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis.

[31]  A. Tedgui,et al.  Circulating microparticles: a potential prognostic marker for atherosclerotic vascular disease. , 2006, Hypertension.

[32]  O. Morel,et al.  [Markers of thrombotic disease: procoagulant microparticles]. , 2007, Annales pharmaceutiques francaises.

[33]  S. Nomura,et al.  High-shear-stress-induced activation of platelets and microparticles enhances expression of cell adhesion molecules in THP-1 and endothelial cells. , 2001, Atherosclerosis.

[34]  Nikos Werner,et al.  Circulating CD31+/Annexin V+ Apoptotic Microparticles Correlate With Coronary Endothelial Function in Patients With Coronary Artery Disease , 2006, Arteriosclerosis, thrombosis, and vascular biology.

[35]  V. Richard,et al.  Sonic hedgehog carried by microparticles corrects endothelial injury through nitric oxide release , 2007, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[36]  M. Razmara,et al.  Glycoprotein IIb/IIIa blockade inhibits platelet aminophospholipid exposure by potentiating translocase and attenuating scramblase activity , 2007, Cellular and Molecular Life Sciences.

[37]  M. U. Nollert,et al.  Leukocyte-leukocyte interactions mediated by platelet microparticles under flow. , 2000, Blood.

[38]  Zwaal Rf,et al.  Platelet phospholipid asymmetry and its significance in hemostasis. , 1983 .

[39]  O. Morel,et al.  Marqueurs des pathologies thrombotiques: Les microparticules procoagulantes☆ , 2007 .

[40]  M. Li,et al.  Different effects of various anti‐GPIIb‐IIIa agents on shear‐induced platelet activation and expression of procoagulant activity , 2003, Journal of thrombosis and haemostasis : JTH.

[41]  H. Hemker,et al.  Generation of prothrombin-converting activity and the exposure of phosphatidylserine at the outer surface of platelets. , 1982, European journal of biochemistry.

[42]  L. Horstman,et al.  Platelet microparticles: a wide-angle perspective. , 1999, Critical reviews in oncology/hematology.

[43]  G. FitzGerald,et al.  Arachidonic Acid in Platelet Microparticles Up-regulates Cyclooxygenase-2-dependent Prostaglandin Formation via a Protein Kinase C/Mitogen-activated Protein Kinase-dependent Pathway* , 1999, The Journal of Biological Chemistry.

[44]  R. Nieuwland,et al.  Microparticles in cardiovascular diseases. , 2003, Cardiovascular research.

[45]  H. Hemker,et al.  The role of phospholipid and factor VIIIa in the activation of bovine factor X. , 1981, The Journal of biological chemistry.

[46]  A. Tedgui,et al.  Role of microparticles in atherothrombosis , 2008, Journal of internal medicine.

[47]  G. FitzGerald,et al.  Modulation of monocyte-endothelial cell interactions by platelet microparticles. , 1998, The Journal of clinical investigation.

[48]  J. Chou,et al.  Accumulation of Tissue Factor into Developing Thrombi In Vivo Is Dependent upon Microparticle P-Selectin Glycoprotein Ligand 1 and Platelet P-Selectin , 2003, The Journal of experimental medicine.

[49]  W. Rathmann,et al.  Impaired glucose tolerance is associated with increased serum concentrations of interleukin 6 and co-regulated acute-phase proteins but not TNF-α or its receptors , 2002, Diabetologia.

[50]  M. Mesri,et al.  Endothelial cell activation by leukocyte microparticles. , 1998, Journal of immunology.

[51]  C. Hack,et al.  Human cell‐derived microparticles promote thrombus formation in vivo in a tissue factor‐dependent manner , 2003, Journal of thrombosis and haemostasis : JTH.

[52]  G. Grau,et al.  In vitro generation of endothelial microparticles and possible prothrombotic activity in patients with lupus anticoagulant. , 1999, The Journal of clinical investigation.

[53]  B. Binder,et al.  Oxidized Membrane Vesicles and Blebs From Apoptotic Cells Contain Biologically Active Oxidized Phospholipids That Induce Monocyte‐Endothelial Interactions , 2002, Arteriosclerosis, thrombosis, and vascular biology.

[54]  Y. Castier,et al.  Cellular origins and thrombogenic activity of microparticles isolated from human atherosclerotic plaques. , 2007, Journal of the American College of Cardiology.

[55]  L. Azevedo,et al.  Circulating microparticles as therapeutic targets in cardiovascular diseases. , 2007, Recent patents on cardiovascular drug discovery.

[56]  R. Nieuwland,et al.  Antigenic characterization of endothelial cell‐derived microparticles and their detection ex vivo , 2003, Journal of thrombosis and haemostasis : JTH.

[57]  R. Nieuwland,et al.  Elevated Numbers of Tissue-Factor Exposing Microparticles Correlate With Components of the Metabolic Syndrome in Uncomplicated Type 2 Diabetes Mellitus , 2002, Circulation.

[58]  J. Dacie,et al.  A Simple Method of Studying the Generation of Thrombin in Recalcified Plasma , 1953, Journal of clinical pathology.

[59]  R. Andriantsitohaina,et al.  Rosiglitazone, a Peroxisome Proliferator-Activated Receptor-γ Agonist, Prevents Microparticle-Induced Vascular Hyporeactivity through the Regulation of Proinflammatory Proteins , 2008, Journal of Pharmacology and Experimental Therapeutics.

[60]  Merlin C. Thomas,et al.  PPAR Agonists and Cardiovascular Disease in Diabetes , 2008, PPAR research.

[61]  A. Baird,et al.  Circulating endothelial microparticles in acute ischemic stroke: a link to severity, lesion volume and outcome , 2006, Journal of thrombosis and haemostasis : JTH.

[62]  V. Fadok,et al.  The role of phosphatidylserine in recognition of apoptotic cells by phagocytes , 1998, Cell Death and Differentiation.

[63]  A. Simon,et al.  Endothelial microparticles in diseases , 2008, Cell and Tissue Research.

[64]  G. Plotnick,et al.  Effect of a single high-fat meal on endothelial function in healthy subjects. , 1997, The American journal of cardiology.

[65]  J. Freyssinet,et al.  Membrane microparticles: two sides of the coin. , 2005, Physiology.

[66]  Patrice Darmon,et al.  Type 1 and type 2 diabetic patients display different patterns of cellular microparticles. , 2002, Diabetes.

[67]  A. Piccin,et al.  Circulating microparticles: pathophysiology and clinical implications. , 2007, Blood reviews.

[68]  E. Sahai,et al.  Membrane blebbing during apoptosis results from caspase-mediated activation of ROCK I , 2001, Nature Cell Biology.

[69]  R. North,et al.  Rapid secretion of interleukin-1β by microvesicle shedding , 2001 .

[70]  S. Virani,et al.  Postprandial Hypertriglyceridemia Increases Circulating Levels of Endothelial Cell Microparticles , 2004, Circulation.

[71]  Christian Weber,et al.  Platelet Microparticles: A Transcellular Delivery System for RANTES Promoting Monocyte Recruitment on Endothelium , 2005, Arteriosclerosis, thrombosis, and vascular biology.

[72]  J. Freyssinet,et al.  Procoagulant membrane microparticles correlate with the severity of pulmonary arterial hypertension. , 2008, American journal of respiratory and critical care medicine.

[73]  G. FitzGerald,et al.  Transcellular activation of platelets and endothelial cells by bioactive lipids in platelet microparticles. , 1997, The Journal of clinical investigation.

[74]  E. Remold-O’Donnell,et al.  HEMOSTASIS , THROMBOSIS , AND VASCULAR BIOLOGY Role of Caspase in a Subset of Human Platelet Activation Responses , 1999 .

[75]  T. Iwasaka,et al.  The effects of pitavastatin, eicosapentaenoic acid and combined therapy on platelet-derived microparticles and adiponectin in hyperlipidemic, diabetic patients , 2009, Platelets.

[76]  Justo Aznar,et al.  Effect of eprosartan on cytoplasmic free calcium mobilization, platelet activation, and microparticle formation in hypertension. , 2004, American journal of hypertension.

[77]  J. Freyssinet,et al.  Procoagulant Microparticles: ‘Criminal Partners’ in Atherothrombosis and Deleterious Cellular Exchanges , 2006, Pathophysiology of Haemostasis and Thrombosis.

[78]  F. George.  Microparticles in vascular diseases. , 2008, Thrombosis research.

[79]  L. Horstman,et al.  Endothelial microparticles correlate with high-risk angiographic lesions in acute coronary syndromes , 2004 .

[80]  R. Andriantsitohaina,et al.  Shed membrane microparticles from circulating and vascular cells in regulating vascular function. , 2005, American journal of physiology. Heart and circulatory physiology.

[81]  R. Nieuwland,et al.  Measuring circulating cell‐derived microparticles , 2004, Journal of thrombosis and haemostasis : JTH.

[82]  A. Hafezi-Moghadam,et al.  Interaction of P-selectin and PSGL-1 generates microparticles that correct hemostasis in a mouse model of hemophilia A , 2003, Nature Medicine.

[83]  L. Horstman,et al.  Elevated endothelial microparticles in thrombotic thrombocytopenic purpura: findings from brain and renal microvascular cell culture and patients with active disease , 2001, British journal of haematology.

[84]  L. Horstman,et al.  More on: cellular microparticles: what are they bad or good for? , 2004, Journal of thrombosis and haemostasis : JTH.

[85]  L. Arnaud,et al.  Standardization of platelet‐derived microparticle counting using calibrated beads and a Cytomics FC500 routine flow cytometer: a first step towards multicenter studies? , 2009, Journal of thrombosis and haemostasis : JTH.

[86]  J. Freyssinet,et al.  Cellular microparticles: a disseminated storage pool of bioactive vascular effectors , 2004, Current opinion in hematology.

[87]  T. Iwasaka,et al.  Losartan and Simvastatin Inhibit Platelet Activation in Hypertensive Patients , 2004, Journal of Thrombosis and Thrombolysis.

[88]  J. Freyssinet,et al.  Shed membrane microparticles with procoagulant potential in human atherosclerotic plaques: a role for apoptosis in plaque thrombogenicity. , 1999, Circulation.

[89]  R. Andriantsitohaina,et al.  Microparticles are vectors of paradoxical information in vascular cells including the endothelium: role in health and diseases. , 2008, Pharmacological reports : PR.

[90]  C. Esmon,et al.  Complement proteins C5b-9 induce vesiculation of the endothelial plasma membrane and expose catalytic surface for assembly of the prothrombinase enzyme complex. , 1990, The Journal of biological chemistry.

[91]  M. Nishikawa,et al.  Effect of Cilostazol on Soluble Adhesion Molecules and Platelet-derived Microparticles in Patients with Diabetes , 1998, Thrombosis and Haemostasis.

[92]  J. Freyssinet.  Cellular microparticles: what are they bad or good for? , 2003, Journal of thrombosis and haemostasis : JTH.

[93]  L. Miguet,et al.  Microparticles: a new tool for plasma membrane sub-cellular proteomic. , 2007, Sub-cellular biochemistry.

[94]  C. Hack,et al.  Cell-derived Microparticles Circulate in Healthy Humans and Support Low Grade Thrombin Generation , 2001, Thrombosis and Haemostasis.

[95]  A. Leroyer,et al.  [Circulating endothelial microparticles: a new marker of vascular injury]. , 2008, Annales de cardiologie et d'angeiologie.

[96]  Chantal M Boulanger,et al.  Circulating endothelial microparticles are associated with vascular dysfunction in patients with end-stage renal failure. , 2005, Journal of the American Society of Nephrology : JASN.

[97]  G. Hankey,et al.  Endothelial and platelet activation in acute ischemic stroke and its etiological subtypes. , 2003, Stroke.

[98]  Laurence Zitvogel,et al.  Exosomes: composition, biogenesis and function , 2002, Nature Reviews Immunology.

[99]  C. Lindsell,et al.  Endothelial microparticle levels are similar in acute ischemic stroke and stroke mimics due to activation and not apoptosis/necrosis. , 2007, Academic emergency medicine : official journal of the Society for Academic Emergency Medicine.

[100]  C. Esmon,et al.  Assembly of the platelet prothrombinase complex is linked to vesiculation of the platelet plasma membrane. Studies in Scott syndrome: an isolated defect in platelet procoagulant activity. , 1989, The Journal of biological chemistry.

[101]  P. Devaux,et al.  Static and dynamic lipid asymmetry in cell membranes. , 1991, Biochemistry.

[102]  H. Prydz,et al.  The changing faces of tissue factor biology , 2007, Thrombosis and Haemostasis.

[103]  M. Toborek,et al.  High-Energy Diets, Fatty Acids and Endothelial Cell Function: Implications for Atherosclerosis , 2001, Journal of the American College of Nutrition.

[104]  J. Freyssinet,et al.  Procoagulant Microparticles: Disrupting the Vascular Homeostasis Equation? , 2006, Arteriosclerosis, thrombosis, and vascular biology.

[105]  J. Freyssinet,et al.  Elevated levels of shed membrane microparticles with procoagulant potential in the peripheral circulating blood of patients with acute coronary syndromes. , 2000, Circulation.

[106]  Giuseppe Rainaldi,et al.  Effect of the administration of n-3 polyunsaturated fatty acids on circulating levels of microparticles in patients with a previous myocardial infarction , 2008, Haematologica.