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Hypertension. 2006;48:180-186
Published online before print June 26, 2006, doi: 10.1161/01.HYP.0000231507.00962.b5
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(Hypertension. 2006;48:180.)
© 2006 American Heart Association, Inc.

Brief Reviews

Circulating Microparticles

A Potential Prognostic Marker for Atherosclerotic Vascular Disease

Chantal M. Boulanger; Nicolas Amabile; Alain Tedgui

From the Institut National de la Santé et de la Recherche Médicale, Cardiovascular Research Center INSERM Lariboisière, Paris, France.

Correspondence to Chantal M. Boulanger, Inserm Unit 689, 41 bd de la Chapelle, 75475 Paris Cedex 10, France. E-mail chantal.boulanger{at}larib.inserm.fr


*    Introduction
up arrowTop
 *Introduction
down arrowMechanisms of MP Formation...
 down arrowDetection and Measurement of...
 down arrowPlasma Levels of MPs...
 down arrowReferences
 
Although the presence of subcellular procoagulant particles in highly centrifuged plasma has been known for many years, it was not until 1967 that shed membrane procoagulant fragments from activated platelets were described by Wolf 1 as "platelet dust." Since then, numerous studies have reported the in vitro release of vesicles from activated or apoptotic cells and their presence in human plasma. Among the different membrane vesicles that cells could release, "microparticles" (MPs) usually refer to those >100 nm in diameter (Figure 1) and derived from the plasma membrane. Smaller vesicles (40 to 100 nm) originating from the endoplasmic membranes are described as "exosomes," and larger particles (>1.5 µm) containing nuclear material are best known as "apoptotic bodies."2–4 Both MPs and apoptotic bodies externalize the anionic phospholipid phosphatidylserine, which plays a crucial role in the activation of both coagulation and complement cascades and supports the binding and activity of secreted phospholipase A2.


Figure 1
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  		Figure 1. Electron microscopy of circulating MPs from patients with acute coronary syndrome (courtesy of Drs Z. Mallat and M. Wassef).

This brief review summarizes the mechanisms leading to the formation and release of MPs, as well as the different approaches to detect their cellular origin in human plasma. This article also discusses the significance of circulating MPs of endothelial origin as both a marker and a trigger of endothelial dysfunction in cardiovascular diseases and the possible prognostic value of plasma MPs to assess cardiovascular risk.


*    Mechanisms of MP Formation and Release
up arrowTop
 up arrowIntroduction
 *Mechanisms of MP Formation...
down arrowDetection and Measurement of...
 down arrowPlasma Levels of MPs...
 down arrowReferences
 
The current knowledge on MP formation derives mainly from experiments on isolated or cultured cells showing that both cell activation and cell apoptosis can lead to MP release. However, in vivo mechanisms involved in MP formation and shedding remain mostly unknown.

The initial step in MP formation requires plasma membrane budding, leading to the formation of membrane blebs. This step requires increases in intracellular calcium, changes in membrane lipid asymmetry, and cytoskeleton protein reorganization (Figure 2).5–7 The formation of membrane vesicles is also associated with the loss of plasma membrane asymmetry, a characteristic of quiescent cells. This leads to exposure of phosphatidylserine on the outer leaflet as a consequence of the calcium-dependent activation of scramblase and floppase/ABC1 and the inhibition of translocase/flippase activities (Figure 2).5,8,9 Phosphatidylserine exposure is not always followed by the release of MPs, which may be regulated by the level of intracellular calcium. Moreover, MPs shedding necessitates modifications in cell structural architecture involving disruption of cytoskeleton proteins organization (Figure 2). In platelets, MP release seems to be controlled by calcium-dependent activation of calpain, a cytosolic cysteine protease involved in rearrangement of cytoskeleton proteins and protein cleavage to activate various receptors and proenzymes.5


Figure 2
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  		Figure 2. Possible pathways leading to membrane budding and MP release.

MP Formation and Release After Cell Activation
Platelets release MPs after activation by thrombin, ADP plus collagen, the complement complex C5b-9, the calcium ionophore A23187, and by high shear stress.10–13 Endothelial cells, monocytes, vascular smooth muscle cells, and hepatocytes can also release MPs after activation by bacterial lipopolysaccharides, inflammatory cytokines including tumor necrosis factor or interleukin-1, the complement complex C5b-9, aggregated low-density lipoproteins, or reactive oxygen species.14–17 Increase in intracellular calcium, most likely at the site of membrane vesicle formation, seems to be a critical step for MP release, but the role of cytoskeleton is not yet fully elucidated (Figure 2).18

Apoptosis-Induced MP Release
MPs released from apoptotic cells may be different in lipid and protein composition from membrane vesicles shed after cell activation and could possibly have different pathophysiological effects. Apoptosis is characterized by cell contraction and DNA fragmentation. Blebbing of the cellular membrane occurs rapidly after cells enter the apoptotic process. Bleb formation depends on actin cytoskeleton and actin-myosin contraction, which is regulated by caspase 3–induced Rho kinase I activation (Figure 2).6,7 Rho kinase activation is required for relocalization of DNA fragments from the nuclear region to membrane blebs, suggesting that MPs from apoptotic cells may contain nuclear material.7,19 Interestingly, statins inhibit MP release from cultured endothelial cells by altering the Rho kinase pathway.20

MP Composition
An important parameter that determines the biological effects of MPs is their protein and lipid composition, which may vary depending on the cell they originate from and the type of stimulus involved in their formation. For instance, the phospholipid composition of MPs isolated from synovial fluid of patients with rheumatoid arthritis differs from that of MPs isolated from the plasma of healthy subjects.21,22 In addition, the degree of phospholipid oxidation varies on the stimulus initiating the release of membrane vesicles.23 MPs also expose proteins that are specific to the cell that they stem from and that can be used for the determination of their cellular origin using antibodies directed against these specific epitopes. Proteomic analyses have revealed that the spectrum of proteins found in MPs released in vitro from cultured cells is influenced in part by the type of stimulus used to trigger cell vesiculation.24 This different pattern of protein expression may be helpful in distinguishing within a subpopulation of circulating MPs those released after apoptotic stimuli from MPs resulting of cell activation.25

Why Do Cells Release MPs?
The reason that cells shed MPs from their main body may be an attempt to reverse the apoptotic process by getting rid of unwanted signaling molecules like the proapoptotic caspase 3.26 The release of MPs would also allow cells to escape phagocytosis by removing quickly from the cell surface "eat-me-signals," such as phosphatidylserine.27 Alternatively, membrane shedding could constitute a signaling entity to phagocytes and neighbor cells, because their interaction modulates inflammation, immune responses, and repair mechanisms.28 Actually, the release of membrane vesicles to signal to neighbor or remote target cells is not a specific property of eukaryotic cells. Bacteria also shed membrane "bubbles" containing toxins aimed at other bacterial strains or their host.29


*    Detection and Measurement of MPs
up arrowTop
 up arrowIntroduction
 up arrowMechanisms of MP Formation...
 *Detection and Measurement of...
down arrowPlasma Levels of MPs...
 down arrowReferences
 
Plasma MPs can be detected and their cellular origin characterized using capture assays or flow cytometry, 2 complementary approaches reviewed in a recent forum.30 A crucial point in circulating MP analysis concerns the preanalytical steps involved in blood sampling and platelet-free plasma preparation.30 Both methods of MP analysis rely on antibody detection of specific cellular markers and annexin V binding of phosphatidylserine. Although the general understanding is that MPs express phosphatidylserine, which is detected by annexin V labeling, some plasma MPs analyzed by flow cytometry express specific markers of their cellular origin but do not bind annexin V even in the presence of high calcium concentrations. For example, in patients with sickle cell disease, circulating endothelial MPs were either positive or negative for annexin V.31 Similar finding were observed for monocyte-derived MPs but not for platelet- or erythrocyte-derived MPs in these patients.31 We observed recently that very few circulating platelet-derived CD41+MPs bind annexin V in some patients with end-stage renal failure, whereas most CD41+ MPs from other patients with the same disease were positive for annexin V (Figure 3).32 Taken all together, these observations suggest that if phosphatidylserine is exposed on the outer leaflet of these annexin V negative MPs, it may be unavailable for annexin V binding as already engaged in some other molecular interactions. Indeed, phosphatidylserine binds with high affinity to lactadherin, a milk-fat globule glycoprotein found on plasma exosomes, or to proteins from the coagulation cascade, such as protein S, an antithrombotic protein cofactor to protein C.33,34 These protein-protein interactions are involved in the phagocytosis of apoptotic cells by macrophages.34,35 Alternatively, the lack of experimental evidence for phosphatidylserine exposure by membrane MPs expressing specific cellular markers may suggest that other pathways in addition to the loss of membrane asymmetry may be involved in their formation and release, but this remains to be demonstrated.


Figure 3
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  		Figure 3. Circulating MPs from patients A and B were gated as events of 100 nm to 1 µm in diameter when compared with calibrator beads (CAL). Platelet MPs were identified as CD41-PC5 ({alpha}IIb integrin) positive events, whereas phosphatidylserine-positive MPs were identified with annexin V- fluorescein isothiocyanate (FITC) labeling in the presence of 5 mmol/L Ca++. Higher concentrations of calcium did not improve annexin V labeling. Control experiments were performed in the presence of annexin V-FITC without calcium and in the presence of CD41 respective isotypic immunoglobulin coupled to PC5 (data not shown). Fluorescence in both controls was restricted to the first decade of FL1 log and FL4 log scales. Colabeling of MPs with annexin V-FITC and CD41-PC5 identified 4 populations: AnnV-CD41-events (in gray), AnnV+CD41-MPs (in orange), AnnV-CD41+MPs (in green), and AnnV+CD41+MPs (in red).


*    Plasma Levels of MPs in Cardiovascular Diseases
up arrowTop
 up arrowIntroduction
 up arrowMechanisms of MP Formation...
 up arrowDetection and Measurement of...
 *Plasma Levels of MPs...
down arrowReferences
 
Circulating levels of MPs are augmented in most cardiovascular diseases when comparing a patient population with a matched group of healthy subjects (Table). Similar findings have been observed in patients with autoimmune and thrombotic diseases. The general consensus is that plasma levels of MPs reflect an equilibrium between their release and their removal by phagocytes. However, there is no information regarding the respective degree of involvement of each pathway in determining plasma levels of MPs in patients with cardiovascular diseases. Interestingly, red blood cell MPs, when injected intravenously to normal rats, are rapidly removed from the circulation by scavenger receptors on Kupffer cells.36


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  		Changes in Plasma Levels of Circulating MPs in Patients With Cardiovascular and Other Diseases

The observation that circulating MPs are increased after acute myocardial infarction (Table) raises the question of whether these MPs might come from the ruptured plaque.37 This possibility is highly unlikely because of the different pattern of cellular origin between plaque and plasma MPs.38 In addition, although MPs are much more abundant in atherosclerotic plaques than in plasma and account for the procoagulant activity of the lipid core,37 at least a dozen large lesions (such as those found in human carotid arteries) would have to rupture simultaneously to fully account for circulating levels of MPs in these patients.38

Circulating MPs are increased in patients with cardiovascular risk factors, such as hypertension, obesity, or cholesterol.39–41 Chronic treatment with antioxidants, such as vitamin C or carvedilol, decreases circulating endothelial MPs in patients with heart failure.42,43 In addition, in vitro experiments have indicated that statins impair endothelial MPs formation, whereas platelet MP release is not affected by aspirin, but reduced by ticlopidine, abciximab, or cilostazol.20,44–47

Circulating MPs: Bystander or Mediator?
Most of the experimental evidence available so far indicates that MPs influence diverse biological functions. However, one should be cautious in interpreting data from studies with MPs generated in vitro or from cultured cells, because they may not be fully representative of those found in vivo. The pattern of proteins found on MPs (which differs between vesiculation stimuli), as well as the level of oxidized lipids, are likely to influence their effects on target cells.23,24 In addition, in vitro concentrations of MPs should be consistent with those found in vivo for MPs of the same cellular origin.

Circulating MPs bear tissue factor at their surface and account for "blood-borne tissue factor."48 They are involved in the formation of tissue factor-platelet hybrids, a critical phenomenon in thrombus propagation, after transfer of tissue factor from leukocyte MPs to platelet membranes.48 This property may not be restricted to leukocyte-derived MPs, because the presence of tissue factor on platelet- erythrocyte- and hematopoietic cell-derived MPs leads also to thrombus propagation in vivo.49,50 In addition, similar observations were reported in vitro regarding endothelial MP-induced tissue factor expression and procoagulant activity in the monocyte cell line THP1.51 In vivo, MPs are captured by thrombus-associated platelets through the interaction of MP P-selectin glycoprotein ligand (PSGL)-1 with platelet P-selectin, leading to a concentration of tissue factor, which initiates and accelerates blood coagulation and fibrin formation.52,53

The first hint that MPs may affect endothelial biology came from studies investigating the effects of MPs derived from in vitro activated platelets on cultured endothelial cells, demonstrating the transcellular delivery of MP arachidonic acid leading to increased expression of endothelial cyclooxygenase type 2.54 Platelet MPs also simulate endothelial cells in vitro to release cytokines and express adhesion molecule.55 In addition, platelet MPs can directly interact with activated vascular endothelial cells by increasing leukocytes/monocytes arrest after transcellular delivery of the chemokine Regulated on Activation, Normal T Expressed and Secreted (RANTES).56

MPs also impair the release of NO from vascular endothelial cells. This was observed on isolated arteries exposed in vitro to circulating concentrations of MPs from patients with acute coronary syndromes, end-stage renal failure, or preeclampsia but not with MPs from healthy subjects.32,57,58 The endothelial dysfunction caused by circulating human MPs seems to be mediated by particles of endothelial origin and is associated with an impaired release of NO but no alteration in endothelial NO synthase expression (Figure 4).32,57 Similar results were reported for MPs released from cultured endothelial cells, smooth muscle cells, or from a lymphocyte cell line, although the molecular mechanisms may be different from those triggered by MPs isolated from human plasma.59–62 Other effects of MPs on vascular reactivity other than impairment of endothelial function have been reported as well. Platelet MPs generated ex vivo cause vascular contraction in vitro by acting as a source of thromboxane A2 for the vessel wall.63 In addition, impaired vascular reactivity because of increased expression of inducible NO synthase and cyclooxygenase-2 (COX2) in smooth muscle cells has been observed in the isolated mouse aorta after exposure to MPs derived from a T-cell line or from circulating MPs isolated from the plasma of diabetic patients.60 Further details on the molecular mechanisms of MP effects on vascular reactivity can be found in Martinez et al.64


Figure 4
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  		Figure 4. Paracrine effect(s) of endothelial MPs predisposing to endothelial dysfunction in vivo.

Finally, endothelial, platelet, and tumor cell-derived MPs seem to be able to stimulate angiogenesis, an effect mediated by reactive oxygen species, metalloproteinases, growth factors such as vascular endothelial growth factor, or sphingomyelin.65–69 Apoptotic bodies from endothelial cells (larger than MPs) could also contribute to tissue repair mechanisms by stimulating the differentiation of progenitor cells.70

Circulating MPs as a Potential Marker for Cardiovascular Diseases
Circulating MPs, mainly those derived from endothelial cells, also express markers of cellular injury, such as the soluble markers intercellular adhesion molecule-1, vascular cell adhesion molecule, E-selectin, or von Willebrand factor. Actually, many of these markers are both true soluble molecules and MP-bound forms, indicating that expression of these hallmarks of cell injury on endothelial MPs could reflect the degree of endothelial dysfunction.71

Recent experimental evidence suggests that plasma level of endothelial MPs is a specific marker of endothelial dysfunction in patients with cardiovascular diseases. Indeed, circulating levels of endothelial CD144+ (VE-cadherin) MPs inversely correlate with the amplitude of the flow-mediated dilatation in the brachial artery of patients with end-stage renal failure, whereas no correlation was observed for platelet or annexin V+ MPs.32 This relationship was independent of age and blood pressure.32 Similar findings were observed in patients with acute coronary syndromes.72 All together, these findings indicate that the more that circulating endothelial MPs are detected, the patient’s arteries are less likely to normally vasodilate in response to increases in flow rate or to acetylcholine. In addition, plasma levels of endothelial MPs correlate with indexes of arterial stiffness in hemodialyzed patients, suggesting that high plasma endothelial MPs also reflect alterations in arterial properties.32 Although the question of whether circulating levels of endothelial MPs cause or result from endothelial dysfunction is still much debated, in vitro evidence indicates that the augmented plasma levels of endothelial MPs, as observed in patients with end-stage renal diseases, could result from endothelial injury or apoptosis.32,73 Cytokines, activated platelets, or oxidized low-density lipoprotein could play a role as well. However, the in vivo stimuli of endothelial vesiculation in patients with cardiovascular diseases remain mostly unknown so far. Plasma endothelial MPs could originate from both circulating mature endothelial cells and endothelial cells lining the vessel wall. It is noteworthy that levels of circulating endothelial cells are also elevated in patients with cardiovascular diseases, as observed for endothelial MPs.74 Alternatively, we cannot exclude the possibility that some circulating MPs originate from progenitor cells, because they share similar marker proteins.

Prognostic Potential of Circulating MPs
Preliminary data indicate that plasma levels of MPs could be of prognostic value for the occurrence of cardiovascular diseases. In a 6-month follow-up study, circulating annexin V+ MPs appear as a robust predictor of the occurrence of secondary myocardial infarction or death in 500 patients with acute coronary syndromes.75 Furthermore, circulating leukocyte-derived MPs, unlike platelet-derived MPs, predict subclinical atherosclerosis burden appreciated by plaque numbers in carotid arteries, abdominal aorta, and femoral arteries in >200 asymptomatic subjects.41

Perspectives
Although the prognostic potential of circulating MPs is still in its infancy, the different studies mentioned above clearly demonstrate that their detection and quantification is an interesting and potentially valuable tool to appreciate cardiovascular risk of asymptomatic patients. Obviously, the response to this important question will first necessitate a standardized approach to MP detection and characterization. In addition, refinement in the detection of MP cellular origin will help shed light on the mechanisms leading to their release in the plasma and/or their clearance.


*    Acknowledgments
 
We thank Clément Nguyen for figure preparation.

Sources of Funding

The authors are part of the European Vascular Genomics Network of Excellence (Contract N° LSHM-CT-2003-503254).

Disclosures

None.

Received March 17, 2006; first decision April 6, 2006; accepted May 31, 2006.


*    References
up arrowTop
 up arrowIntroduction
 up arrowMechanisms of MP Formation...
 up arrowDetection and Measurement of...
 up arrowPlasma Levels of MPs...
 *References
 

  1. Wolf P. The nature and significance of platelet products in human plasma. Br J Haematol. 1967; 13: 269–288.[Medline] [Order article via Infotrieve]
  2. Hugel B, Martinez MC, Kunzelmann C, Freyssinet JM. Membrane microparticles: two sides of the coin. Physiology (Bethesda). 2005; 20: 22–27.[CrossRef][Medline] [Order article via Infotrieve]
  3. Thery C, Zitvogel L, Amigorena S. Exosomes: composition, biogenesis and function. Nat Rev Immunol. 2002; 2: 569–579.[Medline] [Order article via Infotrieve]
  4. VanWijk MJ, VanBavel E, Sturk A, Nieuwland R. Microparticles in cardiovascular diseases. Cardiovasc Res. 2003; 59: 277–287.[Abstract/Free Full Text]
  5. Zwaal RF, Schroit AJ. Pathophysiologic implications of membrane phospholipid asymmetry in blood cells. Blood. 1997; 89: 1121–1132.[Free Full Text]
  6. Sebbagh M, Renvoize C, Hamelin J, Riche N, Bertoglio J, Breard J. Caspase-3-mediated cleavage of ROCK I induces MLC phosphorylation and apoptotic membrane blebbing. Nat Cell Biol. 2001; 3: 346–352.[CrossRef][Medline] [Order article via Infotrieve]
  7. Coleman ML, Sahai EA, Yeo M, Bosch M, Dewar A, Olson MF. Membrane blebbing during apoptosis results from caspase-mediated activation of ROCK I. Nat Cell Biol. 2001; 3: 339–345.[CrossRef][Medline] [Order article via Infotrieve]
  8. Daleke DL. Regulation of transbilayer plasma membrane phospholipid asymmetry. J Lipid Res. 2003; 44: 233–242.[Abstract/Free Full Text]
  9. Hamon Y, Broccardo C, Chambenoit O, Luciani MF, Toti F, Chaslin S, Freyssinet JM, Devaux PF, McNeish J, Marguet D, Chimini G. ABC1 promotes engulfment of apoptotic cells and transbilayer redistribution of phosphatidylserine. Nat Cell Biol. 2000; 2: 399–406.[CrossRef][Medline] [Order article via Infotrieve]
  10. Sims PJ, Faioni EM, Wiedmer T, Shattil SJ. Complement proteins C5b-9 cause release of membrane vesicles from the platelet surface that are enriched in the membrane receptor for coagulation factor Va and express prothrombinase activity. J Biol Chem. 1988; 263: 18205–18212.[Abstract/Free Full Text]
  11. Miyazaki Y, Nomura S, Miyake T, Kagawa H, Kitada C, Taniguchi H, Komiyama Y, Fujimura Y, Ikeda Y, Fukuhara S. High shear stress can initiate both platelet aggregation and shedding of procoagulant containing microparticles. Blood. 1996; 88: 3456–3464.[Abstract/Free Full Text]
  12. Sakariassen KS, Holme PA, Orvim U, Barstad RM, Solum NO, Brosstad FR. Shear-induced platelet activation and platelet microparticle formation in native human blood. Thromb Res. 1998; 92: S33–S41.[CrossRef][Medline] [Order article via Infotrieve]
  13. Reininger AJ, Heijnen HF, Schumann H, Specht HM, Schramm W, Ruggeri ZM. Mechanism of platelet adhesion to von Willebrand factor and microparticle formation under high shear stress. Blood. 2006; 107: 3537–3545.[Abstract/Free Full Text]
  14. Combes V, Simon AC, Grau GE, Arnoux D, Camoin L, Sabatier F, Mutin M, Sanmarco M, Sampol J, Dignat-George F. In vitro generation of endothelial microparticles and possible prothrombotic activity in patients with lupus anticoagulant. J Clin Invest. 1999; 104: 93–102.[Medline] [Order article via Infotrieve]
  15. Satta N, Toti F, Feugeas O, Bohbot A, Dachary-Prigent J, Eschwege V, Hedman H, Freyssinet JM. Monocyte vesiculation is a possible mechanism for dissemination of membrane-associated procoagulant activities and adhesion molecules after stimulation by lipopolysaccharide. J Immunol. 1994; 153: 3245–3255.[Abstract]
  16. Llorente-Cortes V, Otero-Vinas M, Camino-Lopez S, Llampayas O, Badimon L. Aggregated low-density lipoprotein uptake induces membrane tissue factor procoagulant activity and microparticle release in human vascular smooth muscle cells. Circulation. 2004; 110: 452–459.[Abstract/Free Full Text]
  17. Patel KD, Zimmerman GA, Prescott SM, McIntyre TM. Novel leukocyte agonists are released by endothelial cells exposed to peroxide. J Biol Chem. 1992; 267: 15168–15175.[Abstract/Free Full Text]
  18. Miyoshi H, Umeshita K, Sakon M, Imajoh-Ohmi S, Fujitani K, Gotoh M, Oiki E, Kambayashi J, Monden M. Calpain activation in plasma membrane bleb formation during tert-butyl hydroperoxide-induced rat hepatocyte injury. Gastroenterology. 1996; 110: 1897–1904.[CrossRef][Medline] [Order article via Infotrieve]
  19. Holdenrieder S, Stieber P, Bodenmuller H, Busch M, Von Pawel J, Schalhorn A, Nagel D, Seidel D. Circulating nucleosomes in serum. Ann N Y Acad Sci. 2001; 945: 93–102.[Abstract/Free Full Text]
  20. Tramontano AF, O’Leary J, Black AD, Muniyappa R, Cutaia MV, El-Sherif N. 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.[CrossRef][Medline] [Order article via Infotrieve]
  21. Fourcade O, Simon MF, Viode C, Rugani N, Leballe F, Ragab A, Fournie B, Sarda L, Chap H. Secretory phospholipase A2 generates the novel lipid mediator lysophosphatidic acid in membrane microvesicles shed from activated cells. Cell. 1995; 80: 919–927.[CrossRef][Medline] [Order article via Infotrieve]
  22. Weerheim AM, Kolb AM, Sturk A, Nieuwland R. Phospholipid composition of cell-derived microparticles determined by one-dimensional high-performance thin-layer chromatography. Anal Biochem. 2002; 302: 191–198.[CrossRef][Medline] [Order article via Infotrieve]
  23. Huber J, Vales A, Mitulovic G, Blumer M, Schmid R, Witztum JL, Binder BR, Leitinger N. Oxidized membrane vesicles and blebs from apoptotic cells contain biologically active oxidized phospholipids that induce monocyte-endothelial interactions. Arterioscler Thromb Vasc Biol. 2002; 22: 101–107.[Abstract/Free Full Text]
  24. Miguet L, Pacaud K, Felden C, Hugel B, Martinez MC, Freyssinet JM, Herbrecht R, Potier N, van Dorsselaer A, Mauvieux L. Proteomic analysis of malignant lymphocyte membrane microparticles using double ionization coverage optimization. Proteomics. 2006; 6: 153–171.[CrossRef][Medline] [Order article via Infotrieve]
  25. Jimenez JJ, Jy W, Mauro LM, Soderland C, Horstman LL, Ahn YS. Endothelial cells release phenotypically and quantitatively distinct microparticles in activation and apoptosis. Thromb Res. 2003; 109: 175–180.[CrossRef][Medline] [Order article via Infotrieve]
  26. Jy W, Jimenez JJ, Mauro LM, Ahn YS, Newton KR, Mendez AJ, Arnold PI, Schultz DR. Agonist-induced capping of adhesion proteins and microparticle shedding in cultures of human renal microvascular endothelial cells. Endothelium. 2002; 9: 179–189.[CrossRef][Medline] [Order article via Infotrieve]
  27. Fadok VA, Bratton DL, Rose DM, Pearson A, Ezekewitz RA, Henson PM. A receptor for phosphatidylserine-specific clearance of apoptotic cells. Nature. 2000; 405: 85–90.[CrossRef][Medline] [Order article via Infotrieve]
  28. Golpon HA, Fadok VA, Taraseviciene-Stewart L, Scerbavicius R, Sauer C, Welte T, Henson PM, Voelkel NF. Life after corpse engulfment: phagocytosis of apoptotic cells leads to VEGF secretion and cell growth. Faseb J. 2004; 18: 1716–1718.[Abstract/Free Full Text]
  29. Mashburn LM, Whiteley M. Membrane vesicles traffic signals and facilitate group activities in a prokaryote. Nature. 2005; 437: 422–425.[CrossRef][Medline] [Order article via Infotrieve]
  30. Jy W, Horstman LL, Jimenez JJ, Ahn YS, Biro E, Nieuwland R, Sturk A, Dignat-George F, Sabatier F, Camoin-Jau L, Sampol J, Hugel B, Zobairi F, Freyssinet JM, Nomura S, Shet AS, Key NS, Hebbel RP. Measuring circulating cell-derived microparticles. J Thromb Haemost. 2004; 2: 1842–1843.[CrossRef][Medline] [Order article via Infotrieve]
  31. Shet AS, Aras O, Gupta K, Hass MJ, Rausch DJ, Saba N, Koopmeiners L, Key NS, Hebbel RP. Sickle blood contains tissue factor-positive microparticles derived from endothelial cells and monocytes. Blood. 2003; 102: 2678–2683.[Abstract/Free Full Text]
  32. Amabile N, Guerin AP, Leroyer A, Mallat Z, Nguyen C, Boddaert J, London GM, Tedgui A, Boulanger CM. Circulating endothelial microparticles are associated with vascular dysfunction in patients with end-stage renal failure. J Am Soc Nephrol. 2005; 16: 3381–3388.[Abstract/Free Full Text]
  33. Andersen MH, Graversen H, Fedosov SN, Petersen TE, Rasmussen JT. Functional analyses of two cellular binding domains of bovine lactadherin. Biochemistry. 2000; 39: 6200–6206.[CrossRef][Medline] [Order article via Infotrieve]
  34. Anderson HA, Maylock CA, Williams JA, Paweletz CP, Shu H, Shacter E. Serum-derived protein S binds to phosphatidylserine and stimulates the phagocytosis of apoptotic cells. Nat Immunol. 2003; 4: 87–91.[CrossRef][Medline] [Order article via Infotrieve]
  35. Hanayama R, Tanaka M, Miwa K, Shinohara A, Iwamatsu A, Nagata S. Identification of a factor that links apoptotic cells to phagocytes. Nature. 2002; 417: 182–187.[CrossRef][Medline] [Order article via Infotrieve]
  36. Willekens FL, Werre JM, Kruijt JK, Roerdinkholder-Stoelwinder B, Groenen-Dopp YA, van den Bos AG, Bosman GJ, van Berkel TJ. Liver Kupffer cells rapidly remove red blood cell-derived vesicles from the circulation by scavenger receptors. Blood. 2005; 105: 2141–2145.[Abstract/Free Full Text]
  37. Mallat Z, Hugel B, Ohan J, Leseche G, Freyssinet JM, Tedgui A. Shed membrane microparticles with procoagulant potential in human atherosclerotic plaques: a role for apoptosis in plaque thrombogenicity. Circulation. 1999; 99: 348–353.[Abstract/Free Full Text]
  38. Leroyer A, Lesèche G, Nguyen C, Tedgui A, Boulanger CM. Cellular origin of microparticles in human atherosclerotic plaques. Circulation. 2005; 112: U221. Abstract.
  39. Preston RA, Jy W, Jimenez JJ, Mauro LM, Horstman LL, Valle M, Aime G, Ahn YS. Effects of severe hypertension on endothelial and platelet microparticles. Hypertension. 2003; 41: 211–217.[Abstract/Free Full Text]
  40. Diamant M, Nieuwland R, Pablo RF, Sturk A, Smit JW, Radder JK. Elevated numbers of tissue-factor exposing microparticles correlate with components of the metabolic syndrome in uncomplicated type 2 diabetes mellitus. Circulation. 2002; 106: 2442–2447.[Abstract/Free Full Text]
  41. Chironi G, Hugel B, Bihorel Y, Del-Pino M, Gariepy J, Freyssinet JM, Simon A, Tedgui A. Leukocyte-derived microparticles as an independent marker of preclinical carotid atherosclerosis. Circulation. 2005; 112: U126. Abstract.[CrossRef]
  42. Rossig L, Haendeler J, Mallat Z, Hugel B, Freyssinet JM, Tedgui A, Dimmeler S, Zeiher AM. Congestive heart failure induces endothelial cell apoptosis: protective role of carvedilol. J Am Coll Cardiol. 2000; 36: 2081–2089.[Abstract/Free Full Text]
  43. Rossig L, Hoffmann J, Hugel B, Mallat Z, Haase A, Freyssinet JM, Tedgui A, Aicher A, Zeiher AM, Dimmeler S. Vitamin C inhibits endothelial cell apoptosis in congestive heart failure. Circulation. 2001; 104: 2182–2187.[Abstract/Free Full Text]
  44. Zumbach A, Marbet GA, Tsakiris DA. Influence of the genetic background on platelet function, microparticle and thrombin generation in the common laboratory mouse. Platelets. 2001; 12: 496–502.[CrossRef][Medline] [Order article via Infotrieve]
  45. Nomura S, Nagata H, Suzuki M, Iwata K, Kawakatsu T, Kido H, Fukuroi T, Yamaguchi K, Yanabu M, Soga T, Kokawa T, Yansunaga K. Effects of ticlopidine on monoclonal anti-CD9 antibody-induced platelet aggregation and microparticle generation. Thromb Res. 1992; 65: 95–104.[CrossRef][Medline] [Order article via Infotrieve]
  46. Yamazaki M, Uchiyama S, Xiong Y, Nakano T, Nakamura T, Iwata M. Effect of remnant-like particle on shear-induced platelet activation and its inhibition by antiplatelet agents. Thromb Res. 2005; 115: 211–218.[CrossRef][Medline] [Order article via Infotrieve]
  47. Goto S, Tamura N, Li M, Handa M, Ikeda Y, Handa S, Ruggeri ZM. Different effects of various anti-GPIIb-IIIa agents on shear-induced platelet activation and expression of procoagulant activity. J Thromb Haemost. 2003; 1: 2022–2030.[CrossRef][Medline] [Order article via Infotrieve]
  48. Giesen PL, Rauch U, Bohrmann B, Kling D, Roque M, Fallon JT, Badimon JJ, Himber J, Riederer MA, Nemerson Y. Blood-borne tissue factor: another view of thrombosis. Proc Natl Acad Sci U S A. 1999; 96: 2311–2315.[Abstract/Free Full Text]
  49. Biro E, Sturk-Maquelin KN, Vogel GM, Meuleman DG, Smit MJ, Hack CE, Sturk A, Nieuwland R. Human cell-derived microparticles promote thrombus formation in vivo in a tissue factor-dependent manner. J Thromb Haemost. 2003; 1: 2561–2568.[CrossRef][Medline] [Order article via Infotrieve]
  50. Chou J, Mackman N, Merrill-Skoloff G, Pedersen B, Furie BC, Furie B. Hematopoietic cell-derived microparticle tissue factor contributes to fibrin formation during thrombus propagation. Blood. 2004; 104: 3190–3197.[Abstract/Free Full Text]
  51. 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: 3962–3970.[Abstract/Free Full Text]
  52. Furie B, Furie BC. Role of platelet P-selectin and microparticle PSGL-1 in thrombus formation. Trends Mol Med. 2004; 10: 171–178.[CrossRef][Medline] [Order article via Infotrieve]
  53. Hrachovinova I, Cambien B, Hafezi-Moghadam A, Kappelmayer J, Camphausen RT, Widom A, Xia L, Kazazian HH Jr, Schaub RG, McEver RP, Wagner DD. Interaction of P-selectin and PSGL-1 generates microparticles that correct hemostasis in a mouse model of hemophilia A. Nat Med. 2003; 9: 1020–1025.[CrossRef][Medline] [Order article via Infotrieve]
  54. Barry OP, Pratico D, Lawson JA, FitzGerald GA. Transcellular activation of platelets and endothelial cells by bioactive lipids in platelet microparticles. J Clin Invest. 1997; 99: 2118–2127.[Medline] [Order article via Infotrieve]
  55. Nomura S, Tandon NN, Nakamura T, Cone J, Fukuhara S, Kambayashi J. High-shear-stress-induced activation of platelets and microparticles enhances expression of cell adhesion molecules in THP-1 and endothelial cells. Atherosclerosis. 2001; 158: 277–287.[CrossRef][Medline] [Order article via Infotrieve]
  56. Mause SF, von Hundelshausen P, Zernecke A, Koenen RR, Weber C. Platelet microparticles: a transcellular delivery system for RANTES promoting monocyte recruitment on endothelium. Arterioscler Thromb Vasc Biol. 2005; 25: 1512–1518.[Abstract/Free Full Text]
  57. Boulanger CM, Scoazec A, Ebrahimian T, Henry P, Mathieu E, Tedgui A, Mallat Z. Circulating microparticles from patients with myocardial infarction cause endothelial dysfunction. Circulation. 2001; 104: 2649–2652.[Abstract/Free Full Text]
  58. VanWijk MJ, Nieuwland R, Boer K, van der Post JA, VanBavel E, Sturk A. Microparticle subpopulations are increased in preeclampsia: possible involvement in vascular dysfunction? Am J Obstet Gynecol. 2002; 187: 450–456.[CrossRef][Medline] [Order article via Infotrieve]
  59. Martin S, Tesse A, Hugel B, Martinez MC, Morel O, Freyssinet JM, Andriantsitohaina R. Shed membrane particles from T lymphocytes impair endothelial function and regulate endothelial protein expression. Circulation. 2004; 109: 1653–1659.[Abstract/Free Full Text]
  60. Tesse A, Martinez MC, Hugel B, Chalupsky K, Muller CD, Meziani F, Mitolo-Chieppa D, Freyssinet JM, Andriantsitohaina R. Upregulation of proinflammatory proteins through NF-{kappa}B pathway by shed membrane microparticles results in vascular hyporeactivity. Arterioscler Thromb Vasc Biol. 2005; 25: 2522–2527.[Abstract/Free Full Text]
  61. Brodsky SV, Zhang F, Nasjletti A, Goligorsky MS. Endothelium-derived microparticles impair endothelial function in vitro. Am J Physiol Heart Circ Physiol. 2004; 286: H1910–H1915.[Abstract/Free Full Text]
  62. Essayagh S, Brisset AC, Terrisse AD, Dupouy D, Tellier L, Navarro C, Arnal JF, Sie P. Microparticles from apoptotic vascular smooth muscle cells induce endothelial dysfunction, a phenomenon prevented by ß3-integrin antagonists. Thromb Haemost. 2005; 94: 853–858.[Medline] [Order article via Infotrieve]
  63. Pfister SL. Role of platelet microparticles in the production of thromboxane by rabbit pulmonary artery. Hypertension. 2004; 43: 428–433.[Abstract/Free Full Text]
  64. Martinez MC, Tesse A, Zobairi F, Andriantsitohaina R. Shed membrane microparticles from circulating and vascular cells in regulating vascular function. Am J Physiol Heart Circ Physiol. 2005; 288: H1004–H1009.[Abstract/Free Full Text]
  65. Boulanger CM, Tedgui A. Dying for attention: microparticles and angiogenesis. Cardiovasc Res. 2005; 67: 1–3.[Free Full Text]
  66. Brill A, Dashevsky O, Rivo J, Gozal Y, Varon D. Platelet-derived microparticles induce angiogenesis and stimulate post-ischemic revascularization. Cardiovasc Res. 2005; 67: 30–38.[Abstract/Free Full Text]
  67. Kim CW, Lee HM, Lee TH, Kang C, Kleinman HK, Gho YS. Extracellular membrane vesicles from tumor cells promote angiogenesis via sphingomyelin. Cancer Res. 2002; 62: 6312–6317.[Abstract/Free Full Text]
  68. Mezentsev A, Merks RM, O’Riordan E, Chen J, Mendelev N, Goligorsky MS, Brodsky SV. Endothelial microparticles affect angiogenesis in vitro: role of oxidative stress. Am J Physiol Heart Circ Physiol. 2005; 289: H1106–H1114.[Abstract/Free Full Text]
  69. Taraboletti G, D’Ascenzo S, Borsotti P, Giavazzi R, Pavan A, Dolo V. 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.[Abstract/Free Full Text]
  70. Hristov M, Erl W, Linder S, Weber PC. Apoptotic bodies from endothelial cells enhance the number and initiate the differentiation of human endothelial progenitor cells in vitro. Blood. 2004; 104: 2761–2766.[Abstract/Free Full Text]
  71. Horstman LL, Jy W, Jimenez JJ, Ahn YS. Endothelial microparticles as markers of endothelial dysfunction. Front Biosci. 2004; 9: 1118–1135.[Medline] [Order article via Infotrieve]
  72. 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: 112–116.[Abstract/Free Full Text]
  73. Faure V, Dou L, Sabatier F, Cerini C, Sampol J, Berland Y, Brunet P, Dignat-George F. Elevation of circulating endothelial microparticles in patients with chronic renal failure. J Thromb Haemost. 2006; 4: 566–573.[CrossRef][Medline] [Order article via Infotrieve]
  74. Blann AD, Woywodt A, Bertolini F, Bull TM, Buyon JP, Clancy RM, Haubitz M, Hebbel RP, Lip GY, Mancuso P, Sampol J, Solovey A, Dignat-George F. Circulating endothelial cells. Biomarker of vascular disease. Thromb Haemost. 2005; 93: 228–235.[Medline] [Order article via Infotrieve]
  75. Mallat Z, Steg PG, Hugel B, Tanguy ML, Benessiano J, Fox K, Collet J, Henry P, Dabbous O, Montalescot G, Asselin B, Freyssinet JM, Tedgui A. Prognostic value of circulating shed membrane pro-coagulant microparticles in patients with severe acute coronary syndromes. A substudy from the global registry of acute coronary events (GRACE). Circulation. 2004; 110 (Suppl S): 575. Abstract.
  76. Mallat Z, Benamer H, Hugel B, Benessiano J, Steg PG, Freyssinet JM, Tedgui A. 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.[Abstract/Free Full Text]
  77. van der Zee PM, Biro E, Ko Y, de Winter RJ, Hack CE, Sturk A, Nieuwland R. P-selectin- and CD63-exposing platelet microparticles reflect platelet activation in peripheral arterial disease and myocardial infarction. Clin Chem. 2006; 52: 657–664.[Abstract/Free Full Text]
  78. Bernal-Mizrachi L, Jy W, Jimenez JJ, Pastor J, Mauro LM, Horstman LL, de Marchena E, Ahn YS. High levels of circulating endothelial microparticles in patients with acute coronary syndromes. Am Heart J. 2003; 145: 962–970.[CrossRef][Medline] [Order article via Infotrieve]
  79. Garcia S, Chirinos J, Jimenez J, Del Carpio Munoz F, Canoniero M, Jy W, Jimenez J, Horstman L, Ahn Y. Phenotypic assessment of endothelial microparticles in patients with heart failure and after heart transplantation: switch from cell activation to apoptosis. J Heart Lung Transplant. 2005; 24: 2184–2189.[CrossRef][Medline] [Order article via Infotrieve]
  80. Nomura S, Kanazawa S, Fukuhara S. Effects of efonidipine on platelet and monocyte activation markers in hypertensive patients with and without type 2 diabetes mellitus. J Hum Hypertens. 2002; 16: 539–547.[CrossRef][Medline] [Order article via Infotrieve]
  81. Tan KT, Tayebjee MH, Lim HS, Lip GY. Clinically apparent atherosclerotic disease in diabetes is associated with an increase in platelet microparticle levels. Diabet Med. 2005; 22: 1657–1662.[CrossRef][Medline] [Order article via Infotrieve]
  82. Koga H, Sugiyama S, Kugiyama K, Fukushima H, Watanabe K, Sakamoto T, Yoshimura M, Jinnouchi H, Ogawa H. 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: 817–823.[Abstract/Free Full Text]
  83. Sabatier F, Darmon P, Hugel B, Combes V, Sanmarco M, Velut JG, Arnoux D, Charpiot P, Freyssinet JM, Oliver C, Sampol J, Dignat-George F. Type 1 and type 2 diabetic patients display different patterns of cellular microparticles. Diabetes. 2002; 51: 2840–2845.[Abstract/Free Full Text]
  84. Nieuwland R, Berckmans RJ, Rotteveel-Eijkman RC, Maquelin KN, Roozendaal KJ, Jansen PG, ten Have K, Eijsman L, Hack CE, Sturk A. Cell-derived microparticles generated in patients during cardiopulmonary bypass are highly procoagulant. Circulation. 1997; 96: 3534–3541.[Abstract/Free Full Text]
  85. Gonzalez-Quintero VH, Smarkusky LP, Jimenez JJ, Mauro LM, Jy W, Hortsman LL, O’Sullivan MJ, Ahn YS. Elevated plasma endothelial microparticles: preeclampsia versus gestational hypertension. Am J Obstet Gynecol. 2004; 191: 1418–1424.[CrossRef][Medline] [Order article via Infotrieve]
  86. Bretelle F, Sabatier F, Desprez D, Camoin L, Grunebaum L, Combes V, D’Ercole C, Dignat-George F. Circulating microparticles: a marker of procoagulant state in normal pregnancy and pregnancy complicated by preeclampsia or intrauterine growth restriction. Thromb Haemost. 2003; 89: 486–492.[Medline] [Order article via Infotrieve]
  87. Inami N, Nomura S, Kikuchi H, Kajiura T, Yamada K, Nakamori H, Takahashi N, Tsuda N, Hikosaka M, Masaki M, Iwasaka T. P-selectin and platelet-derived microparticles associated with monocyte activation markers in patients with pulmonary embolism. Clin Appl Thromb Hemost. 2003; 9: 309–316.[Abstract/Free Full Text]
  88. Chirinos JA, Heresi GA, Velasquez H, Jy W, Jimenez JJ, Ahn E, Horstman LL, Soriano AO, Zambrano JP, Ahn YS. Elevation of endothelial microparticles, platelets, and leukocyte activation in patients with venous thromboembolism. J Am Coll Cardiol. 2005; 45: 1467–1471.[Abstract/Free Full Text]
  89. Ferreira AC, Peter AA, Mendez AJ, Jimenez JJ, Mauro LM, Chirinos JA, Ghany R, Virani S, Garcia S, Horstman LL, Purow J, Jy W, Ahn YS, de Marchena E. Postprandial hypertriglyceridemia increases circulating levels of endothelial cell microparticles. Circulation. 2004; 110: 3599–3603.[Abstract/Free Full Text]
  90. Minagar A, Jy W, Jimenez JJ, Sheremata WA, Mauro LM, Mao WW, Horstman LL, Ahn YS. Elevated plasma endothelial microparticles in multiple sclerosis. Neurology. 2001; 56: 1319–1324.[Abstract/Free Full Text]
  91. Nieuwland R, Berckmans RJ, McGregor S, Boing AN, Romijn FP, Westendorp RG, Hack CE, Sturk A. Cellular origin and procoagulant properties of microparticles in meningococcal sepsis. Blood. 2000; 95: 930–935.[Abstract/Free Full Text]
  92. Joop K, Berckmans RJ, Nieuwland R, Berkhout J, Romijn FP, Hack CE, Sturk A. Microparticles from patients with multiple organ dysfunction syndrome and sepsis support coagulation through multiple mechanisms. Thromb Haemost. 2001; 85: 810–820.[Medline] [Order article via Infotrieve]
  93. Aupeix K, Hugel B, Martin T, Bischoff P, Lill H, Pasquali JL, Freyssinet JM. The significance of shed membrane particles during programmed cell death in vitro, and in vivo, in HIV-1 infection. J Clin Invest. 1997; 99: 1546–1554.[Medline] [Order article via Infotrieve]
  94. Chamouard P, Desprez D, Hugel B, Kunzelmann C, Gidon-Jeangirard C, Lessard M, Baumann R, Freyssinet JM, Grunebaum L. Circulating cell-derived microparticles in Crohn’s disease. Dig Dis Sci. 2005; 50: 574–580.[CrossRef][Medline] [Order article via Infotrieve]
  95. Simak J, Holada K, Risitano AM, Zivny JH, Young NS, Vostal JG. Elevated circulating endothelial membrane microparticles in paroxysmal nocturnal haemoglobinuria. Br J Haematol. 2004; 125: 804–813.[CrossRef][Medline] [Order article via Infotrieve]
  96. Jimenez JJ, Jy W, Mauro LM, Horstman LL, Soderland C, Ahn YS. Endothelial microparticles released in thrombotic thrombocytopenic purpura express von Willebrand factor and markers of endothelial activation. Br J Haematol. 2003; 123: 896–902.[CrossRef][Medline] [Order article via Infotrieve]



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