Elevated levels of platelet microparticles in carotid atherosclerosis and during the postprandial state (original) (raw)
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The role of platelets in the pathophysiology of atherosclerosis (Review)
Molecular Medicine Reports, 2008
The physiopathology of atherothrombosis is complex. The development and progression of this vascular disease involves the interactive processes of atherosclerotic lesions and the formation of thrombi. In and of itself, atherosclerosis is not deadly; the actual risk lies in the vulnerability of the arteriolosclerotic plaque to breakage. An ulceration, which is the rupture or breakage of the covered plaque, constitutes a complication that favors thrombosis. During these processes platelets are relevant factors, acting with the endothelial and inflammatory cells even at the premature stages of atherogenesis. The interaction of platelets with the endothelial cells (ECs) can occur in two ways: activated platelets joining intact ECs, or resting platelets joining activated ECs. Platelet molecules such as GPIIb-IIIa, CD40, CD40L and P-selectin, as well as microparticle platelets, are important in this process. In this review, the most important mechanisms by which platelets participate in the genesis of atherosclerotic lesions are described. Contents 1. Introduction 2. Platelet physiology 3. Platelets and atherogenesis 4. Conclusion
Journal of Thrombosis and Thrombolysis, 2013
This study investigated the impact of either type 2 diabetes or obesity, separately or in combination, on the absolute amounts of microparticles (MP) and the pathways by which these are associated with either condition. The concentrations of circulating MP derived from platelets (PMP), leukocytes (LMP) and monocytes (MMP), together with their specific activation markers, were compared in 30 subjects who were characterised across 4 cohorts as obese or type 2 diabetes. The subjects with type 2 diabetes had elevated concentrations of total PMP (P = 0.003), and PMP that were fibrinogen-positive (P = 0.04), tissue factor-positive (P \ 0.001), P-selectinpositive (P = 0.03). Type 2 diabetes did not alter either total or activated LMP or MMP. Obesity per se did not impact on any MP measurement. Elevated concentrations of plasma PMP occurred in subjects with type 2 diabetes, whether they were obese or non-obese. In contrast, obesity in the absence of type 2 diabetes had no effect. The increased concentrations of specific marker-positive PMP in the subjects with diabetes might reflect potential pathways by which PMP may contribute to the pathogenesis of atherosclerosis and type 2 diabetes. Keywords Circulating cell-derived microparticles Á Obesity Á Type 2 diabetes mellitus Á Blood platelets Á Cardiovascular diseases
Journal of the American College of Cardiology, 2007
In this study, we evaluated the cellular origins and thrombogenic potential of microparticles. Background Human atherosclerotic plaques contain submicron vesicles (microparticles) released during cell activation or apoptosis. Methods Microparticles were purified from plaques and platelet-free plasma from 26 patients undergoing carotid endarterectomy. Flow cytometry analysis revealed the presence of large amounts of microparticles in plaques but not in healthy vessels. Results Most plaque microparticles originated from leukocytes, of which 29 Ϯ 5% were macrophages, 15 Ϯ 3% lymphocytes, and 8 Ϯ 1% granulocytes. Plaques microparticles also derived from erythrocytes (27 Ϯ 4%), smooth muscle (13 Ϯ 4%) and endothelial cells (8 Ϯ 2%), but not from platelets. Plaques from asymptomatic and symptomatic patients showed no differences in microparticle origins. Microparticles were at least 200-fold more concentrated in plaque than in plasma. Plasma microparticles were primarily platelet-derived in contrast with those of plaque and showed no smooth muscle cell origin. Both plaque and plasma microparticles exposed tissue factor and generated thrombin, but this activity was twice as high in microparticles isolated from plaques, reflecting the thrombogenic contribution of the individual classes of microparticles.
Thrombosis and Haemostasis, 2011
SummaryThe role of platelets in the development of atherosclerosis and obesity-related prothrombotic state is still under investigation. In this cross-sectional cohort study, we measured the levels of different platelet activation markers and evaluated their relationship with carotid intima-media thickness (IMT) along with other atherosclerotic risk factors in obese patients with or without atherosclerotic co-morbidities. We enrolled 154 obese patients, including 98 with either hypertension, type 2 diabetes mellitus or dyslipidaemia, 56 without these co-morbidities and 62 age- and sex-matched healthy controls. Platelet P-selectin expression and the number of platelet-derived microparticles (PMPs) were measured by flow cytometry; soluble P-selectin levels were analysed by ELISA and Thr715Pro P-selectin polymorphism was determined by PCR-RFLP. Carotid IMT was examined by ultrasonography. The levels of platelet activation parameters were significantly elevated in all obese subjects wit...
PLoS ONE, 2013
Aim: The purpose of this project was to evaluate the influence of circulating endothelial progenitor cells (EPCs) and platelet microparticles (PMPs) on blood platelet function in experimental hypertension associated with hypercholesterolemia. Methods: Golden Syrian hamsters were divided in six groups: (i) control, C; (ii) hypertensive-hypercholesterolemic, HH; (iii) 'prevention', HHin-EPCs, HH animals fed a HH diet and treated with EPCs; (iv) 'regression', HHfin-EPCs, HH treated with EPCs after HH feeding; (v) HH treated with PMPs, HH-PMPs, and (vi) HH treated with EPCs and PMPs, HH-EPCs-PMPs. Results: Compared to HH group, the platelets from HHin-EPCs and HHfin-EPCs groups showed a reduction of: (i) activation, reflected by decreased integrin 3b, FAK, PI3K, src protein expression; (ii) secreted molecules as: SDF-1, MCP-1, RANTES, VEGF, PF4, PDGF and (iii) expression of pro-inflammatory molecules as: SDF-1, MCP-1, RANTES, IL-6, IL-1b; TFPI secretion was increased. Compared to HH group, platelets of HH-PMPs group showed increased activation, molecules release and proteins expression. Compared to HH-PMPs group the combination EPCs with PMPs treatment induced a decrease of all investigated platelet molecules, however not comparable with that recorded when EPC individual treatment was applied. Conclusion: EPCs have the ability to reduce platelet activation and to modulate their pro-inflammatory and antithrombogenic properties in hypertension associated with hypercholesterolemia. Although, PMPs have several beneficial effects in combination with EPCs, these did not improve the EPC effects. These findings reveal a new biological role of circulating EPCs in platelet function regulation, and may contribute to understand their cross talk, and the mechanisms of atherosclerosis.
Arteriosclerosis, Thrombosis, and Vascular Biology, 2006
Objective-To clarify circulating microparticles (MP) relationships with preclinical atherosclerosis. Methods and Results-In 216 subjects without cardiovascular disease, we assessed: (1) annexin V-positive, plateletderived, endothelium-derived and leukocyte-derived circulating MP by capture on annexin V, anti-GPIb, anti-CD105, and anti-CD11a antibody-coated wells, respectively; (2) Framingham risk, metabolic syndrome, and low-grade inflammation by risk factors measurement including hsCRP; and subclinical atherosclerosis by ultrasound examination of carotid, abdominal aorta, and femoral arteries. Number of sites with plaque ranged from 0 to 3 and plaque burden was classified into 0 to 1 or 2 to 3 sites disease. Leukocyte-derived MP level was higher in the presence than in the absence of moderate to high Framingham risk (PϽ0.05), metabolic syndrome (PϽ0.01), high C-reactive protein (CRP) (PϽ0.05), or 2-to 3-sites disease (PϽ0.01), and correlated positively with number of metabolic syndrome components (PϽ0.001), tertiles of fibrinogen (PϽ0.001), and number of diseased sites (PϽ0.01). In multivariate analysis, 2-to 3-sites disease was independently associated with leukocyte-derived MP level (PϽ0.05), Framingham risk (PϽ0.001), and metabolic syndrome (PϽ0.01). None of the other MP types correlated with risk markers or atherosclerosis. Conclusions-Leukocyte-derived MP, identified by affinity for CD11a, are increased in subjects with ultrasound evidence of subclinical atherosclerosis, unveiling new directions for atherosclerosis research. (Arterioscler Thromb Vasc Biol. 2006;26:2775-2780.)
Platelets, inflammation and atherosclerosis: Platelets, inflammation and atherosclerosis
J Thromb Haemost, 2007
An expanding body of evidence continues to build on the role of platelets as initial actors in the development of atherosclerotic lesions. Platelets bind to leukocytes and endothelial cells, and initiate monocyte transformation into macrophages. Platelets internalize oxidized phospholipids and promote foam cell formation. Platelets also recruit progenitor cells to the scene that are able to differentiate into foam cells or endothelial cells depending on conditions. Platelets tip the scales in the initiation, development and total extent of atherosclerotic lesions.