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Available from: Olivier Morel, Oct 05, 2015
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    • "Microparticles (MP) are a population of small vesicles derived from host cell plasma membranes, ranging between 0.2–1 µm in diameter. First described by Wolf in 1967 as ‘platelet dust’ [1], these seemingly inert vesicles are present in the circulation of normal healthy subjects and have since been proposed as regulators of vascular homeostasis under physiological conditions [2]. Their enhanced release is triggered by cell injury, activation or apoptosis and various clinical studies have shown an association between MP levels and disease severity [3]–[6]. "
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    ABSTRACT: Septic shock is a severe disease state characterised by the body's life threatening response to infection. Complex interactions between endothelial cells and circulating monocytes are responsible for microvasculature dysfunction contributing to the pathogenesis of this syndrome. Here, we intended to determine whether microparticles derived from activated monocytes contribute towards inflammatory processes and notably vascular permeability. We found that endotoxin stimulation of human monocytes enhances the release of microparticles of varying phenotypes and mRNA contents. Elevated numbers of LPS-induced monocytic microparticles (mMP) expressed CD54 and contained higher levels of transcripts for pro-inflammatory cytokines such as TNF, IL-6 and IL-8. Using a prothrombin time assay, a greater reduction in plasma coagulation time was observed with LPS-induced mMP than with non-stimulated mMP. Co-incubation of mMP with the human brain endothelial cell line hCMEC/D3 triggered their time-dependent uptake and significantly enhanced endothelial microparticle release. Unexpectedly, mMP also modified signalling pathways by diminishing pSrc (tyr416) expression and promoted endothelial monolayer tightness, as demonstrated by endothelial impedance and permeability assays. Altogether, these data strongly suggest that LPS-induced mMP have contrasting effects on the intercellular communication network and display a dual potential: enhanced pro-inflammatory and procoagulant properties, together with protective function of the endothelium.
    PLoS ONE 03/2014; 9(3):e91597. DOI:10.1371/journal.pone.0091597 · 3.23 Impact Factor
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    • "Microparticles (MPs) are small membrane-derived vesicles (0.1–1 µm) shed by activated or apoptotic cells that express anionic phospholipids and an antigenic profile, characteristic of their cellular origin.[1] Circulating MPs are both a result of pathological modifications affecting the vascular compartment, and a pool of bioactive effectors able to modulate vascular homeostasis and contribute to cardiovascular disorders, promoting inflammation, thrombosis and vascular dysfunction themselves.[2] In pathological conditions, MPs are a source of procoagulant activity and are released both from vascular and peripheral blood cells and from atherosclerotic plaque after rupture.[3] Several studies show that both the number and procoagulant activity of MPs increase in patients with cardiovascular disease,[4] including stable and unstable coronary artery disease (CAD).[5] "
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    ABSTRACT: Circulating microparticles (MPs) have been reported to be associated with coronary artery disease (CAD). In this study, we explored the relationship between MPs procoagulant activity and characteristics of atherosclerotic plaque detected by 64-slice computed tomography angiography (CTA). In 127 consecutive patients with CAD but without acute coronary syndrome and who underwent 64-slice CTA, MPs procoagulant activity in plasma (by a thrombin generation test), soluble form of lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) and N(epsilon)-(carboxymethyl) lysine (CML) circulating levels (by ELISA) were measured. A quantitative volumetric analysis of the lumen and plaque burden of the vessel wall (soft and calcific components), for the three major coronary vessels, was performed. The patients were classified in three groups according to the presence of calcium volume: non-calcified plaque (NCP) group (calcium volume (%) = 0), moderate calcified plaque (MCP) group (0 < calcium volume (%) < 1), and calcified plaque (CP) group (calcium volume (%) ≥ 1). MPs procoagulant activity and CML levels were higher in MCP group than in CP or NCP group (P = 0.009 and P = 0.027, respectively). MPs procoagulant activity was positively associated with CML (r = 0.317, P < 0.0001) and sLOX-1 levels (r = 0.216, P = 0.0025). MPs procoagulant activity was higher in the MCP patient group and correlated positively with sLOX-1 and CML levels, suggesting that it may characterize a state of blood vulnerability that may locally precipitate plaque instability and increase the risk of subsequent major cardiovascular events.
    Journal of Geriatric Cardiology 03/2014; 11(1):13-9. DOI:10.3969/j.issn.1671-5411.2014.01.008 · 1.40 Impact Factor
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    • "In vitro studies of platelet function in sepsis and experimental endotoxemia have revealed that addition of septic plasma to control platelets can induce a pathologic response [28], [50], and that removal of septic plasma from patient platelets can restore platelet function [28]. Also, fibrinolytic activity may both be enhanced and inhibited by circulating blood cells and cell-derived microparticles [51]–[55]. Thus, platelets protect the clot against tissue-type plasminogen activator (tPA)-induced fibrinolysis [51] and enhance the antifibrinolytic effect of exogenous FXIII in vitro [52] and red blood cells confer lytic resistance to fibrin resulting from modified fibrin structure and impaired plasminogen activation [56]. In contrast, other blood and endothelial cells, and their derived microparticles, promote fibrinolysis through the action of cell-associated urokinase-type plasminogen activator (uPA) and tPA [53]–[55] and leukocytes promote fibrinolysis through various alternative pathways [57]. "
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    ABSTRACT: Sepsis induces early activation of coagulation and fibrinolysis followed by late fibrinolytic shutdown and progressive endothelial damage. The aim of the present study was to investigate and compare the functional hemostatic response in whole blood and plasma during experimental human endotoxemia by the platelet function analyzer, Multiplate and by standard and modified thrombelastography (TEG). Prospective physiologic study of nine healthy male volunteers undergoing endotoxemia by means of a 4-hour infusion of E. coli lipopolysaccharide (LPS, 0.5 ng/kg/hour), with blood sampled at baseline and at 4 h and 6 h. Physiological and standard biochemical data and coagulation tests, TEG (whole blood: TEG, heparinase-TEG, Functional Fibrinogen; plasma: TEG±tissue-type plasminogen activator (tPA)) and Multiplate (TRAPtest, ADPtest, ASPItest, COLtest) were recorded. Mixed models with Tukey post hoc tests and correlations were applied. Endotoxemia induced acute SIRS with increased HR, temperature, WBC, CRP and procalcitonin and decreased blood pressure. It also induced a hemostatic response with platelet consumption and reduced APTT while INR increased (all p<0.05). Platelet aggregation decreased (all tests, p<0.05), whereas TEG whole blood clot firmness increased (G, p = 0.05). Furthermore, during endotoxemia (4 h), whole blood fibrinolysis increased (clot lysis time (CLT), p<0.001) and Functional Fibrinogen clot strength decreased (p = 0.049). After endotoxemia (6 h), whole blood fibrinolysis was reduced (CLT, p<0.05). In contrast to findings in whole blood, the plasma fibrin clot became progressively more resistant towards tPA-induced fibrinolysis at both 4 h and 6 h (p<0.001). Endotoxemia induced a hemostatic response with reduced primary but enhanced secondary hemostasis, enhanced early fibrinolysis and fibrinogen consumption followed by downregulation of fibrinolysis, with a discrepant fibrinolytic response in plasma and whole blood. The finding that blood cells are critically involved in the vasculo-fibrinolytic response to acute inflammation is important given that disturbances in the vascular system contribute significantly to morbidity and mortality in critically ill patients.
    PLoS ONE 03/2013; 8(3):e59368. DOI:10.1371/journal.pone.0059368 · 3.23 Impact Factor
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