Monocyte-derived Microparticles Research Articles

Presurgical circulating platelet-derived microparticles level as a risk factor of blood transfusion in patients with valve heart disease undergoing cardiac surgery

BackgroundCell-derived microparticles (MPs) are membrane vesicles that have emerged as a potential biomarker for various diseases and their clinical complications. This study investigates the role of MPs as a risk factor for blood transfusion in patients with valve heart disease undergoing cardiac surgery. MethodsForty adult patients undergoing heart valve surgery with cardiopulmonary bypass (CPB) were enrolled, and venous blood samples were collected prior to surgical incision. Plasma rich in MPs was prepared by double centrifugation, and the concentration of MPs was determined using the Bradford method. Flow cytometry analysis was performed to determine MPs count and phenotype. Patients were divided into “with transfusion” (n = 18) and “without transfusion” (n = 22) groups based on red blood cell (RBC) transfusion. ResultsThere was no significant difference in MPs concentration between the “with transfusion” and “without transfusion” groups. Although the count of preoperative platelet-derived MPs (PMPs), monocyte-derived MPs (MMPs), and red cell-derived MPs (RMPs) was higher in “without transfusion” group, these differences were not statistically significant. The preoperative PMPs count was negatively correlated with RBC transfusion (P = 0.005, r = -0.65). Multivariate logistic regression analysis revealed that the count of CD41+ PMPs, Hemoglobin (Hb), and RBC count were risk factors for RBC transfusion. ConclusionThis study suggests that the presurgical levels of PMPs, Hb, and RBC count can serve as risk factors of RBC transfusion in patients with valve heart disease undergoing cardiac surgery. The findings provide insights into the potential use of MPs as biomarkers for blood transfusion prediction in cardiac surgery.

Microparticles: potential new contributors to the pathogenesis of systemic sclerosis?

BackgroundMicroparticles (MPs) are membrane-derived vesicles released from cells undergoing activation or apoptosis with diverse proinflammatory and prothrombotic activities, that have been implicated in the pathogenesis of systemic sclerosis (SSc). We aimed to evaluate the plasma levels of platelet-derived microparticles (PMPs), endothelial cell-derived microparticles (EMPs), and monocyte-derived microparticles (MMPs) in SSc patients, and the association between MPs and the clinical features of SSc.MethodsIn this cross-sectional study, 70 patients with SSc and 35 age- and sex-matched healthy controls were evaluated. Clinical and nailfold capillaroscopy (NFC) data were obtained from all patients. Plasma levels of PMPs (CD42+/31+), EMPs (CD105+), and MMPs (CD14+) were quantified by flow cytometry.ResultsPatients were mainly females (90%), with a mean age of 48.9 years old. PMP, EMP, and MMP levels were significantly increased in SSc patients compared to controls (79.2% ± 17.3% vs. 71.0% ± 19.8%, p = 0.033; 43.5% ± 8.7% vs. 37.8% ± 10.4%, p = 0.004; and 3.5% ± 1.3% vs. 1.1% ± 0.5%, p < 0.0001, respectively). PMP levels were significantly higher in patients with positive anti-topoisomerase-I antibodies (p = 0.030) and in patients with a disease duration > 3 years (p = 0.038). EMP levels were lower in patients with a higher modified Rodnan skin score (p = 0.015), and in those with an avascular score > 1.5 in NFC (p = 0.042).ConclusionThe increased levels of PMPs, EMPs and MMPs in scleroderma patients might indicate a possible role for these agents in the pathogenesis of this challenging disease.

Annexin V− and tissue factor+ microparticles as biomarkers for predicting deep vein thrombosis in patients after joint arthroplasty

ObjectiveVenous thromboembolism (VTE) is a common and severe complication of joint arthroplasty. Microparticles (MPs) containing phosphatidylserine (PS) and tissue factor (TF) can trigger coagulation in VTE. This study aims to measure and compare MP levels in joint arthroplasty patients with and without VTE. MethodsThis prospective cohort study enrolled 181 patients who underwent joint arthroplasty. Ultrasound examination was used to diagnose VTE on preoperative day 0 and postoperative day 6. MPs were analysed using transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and flow cytometry. The levels of platelet-derived microparticles (PMPs), endothelial cell-derived microparticles (EMPs), granulocyte-derived microparticles (GMPs), red cell-derived microparticles (RMPs), monocyte-derived microparticles (MMPs), Annexin V+ MPs (AV+ MPs), and tissue factor+ MPs (TF+ MPs) derived from five kinds of MPs were measured on day 0 (before surgery), 1, 2, 3, 4, 5, and 6 after surgery. ResultsThe levels of AV-TF+ EMPs and AV-TF+ MMPs were significantly increased in patients with VTE on postoperative day 5 compared to those without VTE (P = 0.031 and P = 0.031, respectively). ConclusionAV-TF+ MPs may indicate the development of VTE and serve as predictive markers in joint arthroplasty patients.

Monocytic microparticles enhance proinflammatory cytokine secretion by monocytes and activate endothelial cells

Background: Monocytic microparticles (mMPs) are microparticles derived from activated human monocytes and play an important role in cell-to-cell communication in the circulation. Endothelial cells also exist in the circulation and are thought to have a complex interaction with the released mMPs. Both mMPs and endothelial cells are important players in inflammation. However, the underlying mechanism exerted by mMPs in modulating monocyte and endothelial cell activation during inflammation remains unclear. Methods: Monocytic THP-1 and U937 cells, as well as human blood monocytes, were cultured in the presence or absence of their corresponding mMPs prior to assessing tumor necrosis factor-a (TNF-a), interleukin 1b (IL-1b ), and interleukin 6 (IL-6) secretion. Upon the culture of human umbilical vein endothelial cells (HUVECs) in the presence or absence of mMPs, the expression of CD31, intracellular adhesion molecule 1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1) by HUVECs and endothelial microparticles (eMPs) was assessed. Results: Our results showed that THP-1 cells and stimulated monocyte-derived mMPs enhanced IL-1b and IL-6 secretion, respectively. Additionally, mMPs derived from stimulated monocytes enhanced the expression of CD31, ICAM-1, and VCAM-1 by HUVECs and increased the release of eMPs. Conclusion: These data suggest that mMPs may exacerbate inflammation through IL-1b and IL-6 activity and facilitate monocyte recruitment to inflammatory sites via CD31, ICAM-1, and VCAM-1.

Atherosclerosis severity in patients with familial hypercholesterolemia: The role of T and B lymphocytes

Familial hypercholesterolemia (FH) is characterized by lifelong exposure to high LDL-c concentrations and premature atherosclerotic cardiovascular disease; nevertheless, disease severity can be heterogeneous.We aimed at evaluating if the immune-inflammatory system could modulate atherosclerosis burden in FH. From a cohort of subjects with confirmed FH (Dutch Lipid Clinic Network and genotype), 92 patients receiving high-intensity lipid-lowering therapy (statin±ezetimibe) were included. The extension and severity of coronary atherosclerosis was assessed by standardized reporting systems (CAD-RADS) for coronary computed tomography angiography (CCTA) and coronary artery calcium (CAC) scores. Lipids, apolipoproteins, anti-oxLDL and anti-apolipoprotein B-D peptide (anti-ApoB-D) autoantibodies (IgM and IgG), lymphocytes subtypes, platelet, monocyte and endothelial microparticles (MP), IgM levels (circulating or produced by B1 cells) and cytokines in the supernatant of cultured cells were determined. Multiple linear regression models evaluated associations of these biomarkers with CAC and CAD-RADS scores. In univariate analysis CAC correlated with age, systolic blood pressure, TCD4+ cells, and titers of IgM anti-ApoB-D. In multiple linear regression [ANOVA F=2.976; p=0.024; R2=0.082), CD4+T lymphocytes (B=35.289; beta=0.277; p=0.010; 95%CI for B 8.727 to 61.851), was independently associated with CAC. CAD-RADS correlated with age, systolic blood pressure, titers of IgM anti-ApoB-D, and endothelial MP in univariate analysis. In multiple linear regression, [ANOVA F=2.790; p=0.032; R2=0.119), only age (B=0.027; beta=0.234; p=0.049; 95% CI for B 0.000 to 0.053) was independent predictor. In subjects with FH, under high-intensity lipid-lowering therapy, age and CD4+T cells were associated to atherosclerosis burden.

Circulating endothelial microparticles: a promising biomarker of acute kidney injury after cardiac surgery with cardiopulmonary bypass

BackgroundCurrent diagnostic strategies for acute kidney injury (AKI) after cardiac surgery with cardiopulmonary bypass (CPB) are nonspecific and limited. Previously, we demonstrated that circulating microparticles (MPs) in patients with valve heart disease (VHD) and congenital heart diseases (CHD) induce endothelial dysfunction and neutrophil chemotaxis, which may result in kidney injury. We also found that circulating MPs increase after cardiac surgery with CPB and are related to cardiac function. However, the relationship between circulating MPs and AKI after CPB is unknown.MethodsEighty-five patients undergoing cardiac surgery with CPB were enrolled. Patients were divided into AKI and non-AKI groups based on the serum creatinine levels at 12 h and 3 d post-CPB. Circulating MPs were isolated from plasma, and their levels including its subtypes were detected by flow cytometer. Independent risk factors for the CPB-associated AKI (CPB-AKI) were determined by multivariate logistic regression analysis. Receiver operating characteristic (ROC) analysis was used to measure the prognostic potential of CPB-AKI.ResultsThe morbidity of AKI at 12 h and 3 d after cardiac surgery with CPB was 40% and 31.76%, respectively. The concentrations of total MPs and platelet-derived MPs (PMP) remained unchanged at 12 h and then increased at 3 d post-CPB, while that of endothelial-derived MPs (EMP) increased at both time points. In patients with AKI, PMP and EMP were elevated compared with the patients without AKI. However, no significant change was detected on monocyte-derived MPs (MMP) at 12 h and 3 d post-CPB. The logistic regression analysis showed that EMP was the independent risk factor for AKI both at 12 h and 3 d post-CPB. The area under ROC for the concentrations of EMP at 12 h and 3 d post-CPB was 0.86 and 0.91, with the specificity up to 0.88 and 0.91, respectively.ConclusionsCirculating EMP may serve as a potential biomarker of AKI after cardiac surgery with CPB.

Monocyte-derived microparticles stimulate alveolar macrophages from patients with sarcoidosis: modulation by PPARγ

article: Monocyte-derived microparticles stimulate alveolar macrophages from patients with sarcoidosis: modulation by PPARγ - Minerva Biotecnologica 2020 December;32(4):143-9 - Minerva Medica - Journals

Impact of activated monocyte and endothelial dysfunction on coagulopathy in Egyptian adult beta thalassemic patients.

The mechanism of the well observed hypercoagulability and high incidence of Thromboembolic Events (TE) in β- thalassemia patients has not been fully elucidated. This study aimed to evaluate evaluate the endothelial dysfunction and monocyte activation among adult Egyptian β-thalassemic patients and assess their role in the hypercoagulability and development of TE. A total of 40 adults patients with bthalassemics and 20 healthy age and sex-matched controls were assessed for endothelial dysfunction using serum Von Willebrand Factor Antigen (VWFAg) and for monocytic activation using flow cytometric assessment of CD14 monocyte microparticles and CD11b activated monocytes. The VWF:Ag level was significantly higher among thalassemic patients (P<0.001) and was positively correlated to development of TE (P<0.05). There was no significance difference for CD14 between patients and controls (P>0.5) and CD11b was higher in controls (P=0.004) with no significant correlation between both and TE development (P>0.05). VWF:Ag is increased in thalassemic patients and could be used as a risk factor for thrombosis in these patients, while no identified role of activated monocytes in thrombotic tendency in such patients.

Advanced chronic kidney disease is associated with higher serum concentration of monocyte microparticles

Advanced chronic kidney disease is associated with high rates of cardiovascular disease. Considering the crucial role of capillaries in renal function, our study aimed to evaluate microparticles related to vascular physiology examining the link between stages of chronic kidney disease with circulating endothelial (EMP), platelet (PMP) and monocytic (MMP) microparticles. Cross-sectional study with blinded endpoints included subjects of both sexes, aged 40–75 years (n = 247), with established cardiovascular disease (coronary heart disease, ischemic stroke, or peripheral artery disease). They were stratified 1:1 by the presence or absence of decreased glomerular filtration rate (GFR < 60 mL/min/1.73 m2) estimated by the CKD-EPI criteria, and according to the stages of CKD. Microparticles were quantified by flow-cytometry using specific antibodies to identify endothelial, platelet, and monocytic derived microparticles. Higher percentages of circulating MMP (p = 0.036), but not for EMP or PMP, were observed in subjects with reduced GFR. Circulating MMP were also related to the stages of chronic kidney disease (trend analysis across renal stages, p = 0.038). Higher percentages of circulating MMP were found in subjects with reduced GFR, and their percentages were progressively higher according to the stage of chronic renal function.

Significance of neutrophil microparticles in ischaemia-reperfusion: Pro-inflammatory effectors of endothelial senescence and vascular dysfunction.

Endothelial senescence is an emerging cause of vascular dysfunction. Because microparticles are effectors of endothelial inflammation and vascular injury after ischaemia‐reperfusion, we examined leucocyte‐derived microparticles of spleen origin as possible contributors. Microparticles were generated from primary rat splenocytes by either lipopolysaccharide or phorbol‐myristate‐acetate/calcium ionophore, under conditions mimicking innate and adaptive immune responses. Incubation of primary porcine coronary endothelial cells with either type of microparticles, but not with those from unstimulated splenocytes, leads to a similar threefold raise in senescence‐associated β‐galactosidase activity within 48 hours, indicating accelerated senescence, to endothelial oxidative stress, and a fivefold and threefold increase in p21 and p16 senescence markers after 24 hours. After 12‐hour incubation, the endothelial‐dependent relaxation of coronary artery rings was reduced by 50%, at distinct optimal microparticle concentration. In vitro, microparticles were pro‐thrombotic by up‐regulating the local angiotensin system, by prompting tissue factor activity and a secondary generation of pro‐coagulant endothelial microparticles. They initiated an early pro‐inflammatory response by inducing phosphorylation of NF‐κB, MAP kinases and Akt after 1 hour, and up‐regulated VCAM‐1 and ICAM‐1 at 24 hours. Accordingly, VCAM‐1 and COX‐2 were also up‐regulated in the coronary artery endothelium and eNOS down‐regulated. Lipopolysaccharide specifically favoured the shedding of neutrophil‐ and monocyte‐derived microparticles. A 80% immuno‐depletion of neutrophil microparticles reduced endothelial senescence by 55%, indicating a key role. Altogether, data suggest that microparticles from activated splenocytes prompt early pro‐inflammatory, pro‐coagulant and pro‐senescent responses in endothelial cells through redox‐sensitive pathways. The control of neutrophil shedding could preserve the endothelium at site of ischaemia‐reperfusion–driven inflammation and delay its dysfunction.

Use of Thrombodynamics for revealing the participation of platelet, erythrocyte, endothelial, and monocyte microparticles in coagulation activation and propagation.

Background and objectiveFor many pathological states, microparticles are supposed to be one of the causes of hypercoagulation. Although there are some indirect data about microparticles participation in coagulation activation and propagation, the integral hemostasis test Thrombodynamics allows to measure micropaticles participation in these two coagulation phases directly. Demonstrates microparticles participation in coagulation activation by influence on the appearance of coagulation centres in the plasma volume and the rate of clot growth from the surface with immobilized tissue factor.Methods: Microparticles were obtained from platelets and erythrocytes by stimulation with thrombin receptor-activating peptide (SFLLRN) and calcium ionophore (A23187), respectively, from monocytes, endothelial HUVEC culture and monocytic THP cell culture by stimulation with lipopolysaccharides. Microparticles were counted by flow cytometry and titrated in microparticle-depleted normal plasma in the Thrombodynamics test.ResultsMonocyte microparticles induced the appearance of clotting centres through the TF pathway at concentrations approximately 100-fold lower than platelet and erythrocyte microparticles, which activated plasma by the contact pathway. For endothelial microparticles, both activation pathways were essential, and their activity was intermediate. Monocyte microparticles induced plasma clotting by the appearance of hundreds of clots with an extremely slow growth rate, while erythrocyte microparticles induced the appearance of a few clots with a growth rate similar to that from surface covered with high-density tissue factor. Patterns of clotting induced by platelet and endothelial microparticles were intermediate. Platelet, erythrocyte and endothelial microparticles impacts on the rate of clot growth from the surface with tissue factor did not differ significantly within the 0–200·103/ul range of microparticles concentrations. However, at concentrations greater than 500·103/ul, erythrocyte microparticles increased the stationary clot growth rate to significantly higher levels than do platelet microparticles or artificial phospholipid vesicles consisting of phosphatidylcholine and phosphatidylserine.ConclusionMicroparticles of different origins demonstrated qualitatively different characteristics related to coagulation activation and propagation.

Clinical Significance of Factor XIII Activity and Monocyte-Derived Microparticles in Cancer Patients.

BackgroundThe aim was to evaluate factor XIII activity (FXIIIa) and monocyte-derived microparticles (MDMPs) in cancer patients.MethodsIn total, 138 cancer patients (31 malignant lymphomas, 39 multiple myelomas, and 68 lung cancers) were analyzed. We measured various biomarkers including FXIIIa and MDMPs.ResultsThe values of endothelial activation markers, monocyte chemoattractant peptide (MCP)-1, soluble (s)CD14, and MDMPs were higher in cancer patients than in non-cancerous controls. MCP-1, sCD14, and MDMPs were significantly correlated with FXIIIa in multivariate analysis in cancer patients. In addition, MCP-1, sCD14, and MDMP levels were significantly increased in the high FXIIIa group of patients. Finally, the survival rate of the high FXIIIa group was significantly poor in the Kaplan–Meier analysis.ConclusionThese results suggest that abnormal levels of FXIIIa and MDMPs may offer promise as poor prognostic factors in cancer patients.

Microparticle Responses to Aerobic Exercise and Meal Consumption in Healthy Men.

Microparticles (MP) are shed extracellular vesicles that express the prothrombotic tissue factor (TF). Aerobic exercise may reduce MP count and TF expression. This study investigated the impact of acute running or rest followed by standardized meal consumption on MP phenotypes and TF expression. Fifteen males (age, 22.9 ± 3.3 yr; body mass, 81.9 ± 11.4 kg; V˙O2max, 54.9 ± 6.5 mL·kg·min; mean ± SD) completed 1 h of running (70% V˙O2max) or rest at 9:00 AM and consumed a standardized meal (1170 kcal, 43% CHO, 17% PRO, 40% fat) at 10:45 AM. Venous blood samples were taken at 9:00 AM, 10:00 AM, and 11:30 AM. The MP concentration, diameter, phenotypes, and TF expression were assessed using nanoparticle tracking analysis and flow cytometry. Nanoparticle tracking analysis identified no changes in MP concentration or diameter in response to time or trial. Flow cytometry revealed total MP count increased from 9:00 AM to 10:00 AM (1.62 ± 2.28 to 1.74 ± 2.61 × 10 L, P = 0.016, effect size (η) = 0.105), but was unaffected by trial. TF platelet-derived MP % reduced from 9:00 AM to 10:00 AM (44.0% ± 21.2% to 21.5% ± 9.3%, P = 0.001, η = 0.582) after exercise only (control, 36.8% ± 18.2% to 34.9% ± 11.9%; P = 0.972). TF neutrophil-derived MP percentage reduced from 9:00 AM to 11:30 AM (42.3% ± 17.2% to 25.1% ± 14.9%; P = 0.048, η = 0.801) in the exercise trial only (control, 28.5% ± 15.7% to 32.2% ± 9.6%; P = 0.508). Running induced a significant reduction in %TF platelet and neutrophil MP, suggesting a transient reduction in cardiovascular risk via reduced TF-stimulated thrombosis. This requires further investigation over longer periods in cardiovascular disease populations.

Diagnostic and prognostic relevance of microparticles in peripheral and uterine blood of patients with endometrial cancer

Exosomes - microvesicles which are secreted by living cells - can be produced from different cell types and detected in various body fluids. They are the carriers of intercellular information which regulate tumor microenvironment and are considered to be involved in tumor progression and metastasis. Cancer cells can secrete more exosomes than healthy cells, and are expected to be potential tools for tumor diagnosis and treatment. In this report, we present the results of microparticle analysis in peripheral and uterine blood of patients with endometrial cancer. To the best of our knowledge, this study has been the first to report microvesicle status in peripheral and uterine blood samples. The aim of the study was to determine the amount of total (TF+), endothelial (CD144+) and monocytic (CD14+) microparticles. The counting of the selected microparticles in citrate plasma was performed using flow cytometry on the BD Canto II cytometer. We found that the total amount of microparticles in cancer patients was much higher than in healthy controls. Moreover, microparticle count in uterine blood was higher than in peripheral blood of patients with endometrial cancer. We also demonstrated that the amount of microparticles correlates with the histologic grade and clinical stage of the tumor. The most interesting finding in this work was the high level of TF, CD144 and CD14 MPs in uterine blood samples. Thus we can consider the monocyte-macrophage-derived MPs as a candidate marker of endometrial cancer and maybe very critical part of the endometrial carcinogenesis.

The Release of Monocyte-Derived Tissue Factor-Positive Microparticles Contributes to a Hypercoagulable State in Idiopathic Membranous Nephropathy.

Aim: Idiopathic membranous nephropathy (IMN) is an immune-mediated inflammatory disease characterized by a high risk of thromboembolic complications. Microparticles (MPs), a type of extracellular vesicles, have procoagulant properties, especially when they display tissue factor (TF). This study aimed to investigate whether circulating TF-positive MPs contributed to the hypercoagulable state in patients with IMN.Methods: Twenty adult IMN patients and fourteen healthy subjects were included in the study. The basic indexes of a routine biochemical examination and coagulative function were determined. The plasma levels of MPs were detected by flow cytometry, and TF activity of MPs was examined using an assay kit. The plasma levels of lipopolysaccharide (LPS) were measured by an enzyme-linked immunosorbent assay.Results: Total circulating MPs were not increased in patients with IMN compared with healthy controls. Circulating CD14+/TF+MPs were significantly increased in IMN patients, but this achieved significance was not observed in CD41+/TF+MPs between the two groups. Interestingly, the circulating TF-positive MPs were increased significantly. Plasma MPs TF assays revealed high procoagulant activity, which was positively associated with the D-dimer level in IMN. In addition, circulating LPS in IMN patients were significantly higher than those in the controls. Furthermore, after two hours' incubation with healthy whole blood, LPS enhanced the release of circulating TF-positive MPs and the TF activity of MPs.Conclusion: Increased circulating LPS may mediate the release of monocyte-derived TF-positive MPs, which further contributes to the hypercoagulable state in IMN patients. These findings provide an additional mechanism by which patients with IMN have a higher risk of thromboembolic complication.

Role of microparticles derived from monocytes, endothelial cells and platelets in the exacerbation of COPD.

BackgroundMicroparticles (MPs) are shedding membrane vesicles released from activated blood and endothelial cells under inflammatory conditions. The role of endothelial MPs (EMPs) in pathophysiology of COPD is relatively well known. However, the release and function of MPs of other cellular origins, eg, platelets, red blood cells and leukocytes, are not clearly evaluated in COPD.PurposeThe aim of this study was to measure EMPs and other cell-derived circulating MPs in stable and exacerbated COPD patients.Patients and methodsA total of 50 patients with COPD and 19 healthy volunteers were enrolled in the study. EMPs (CD31+, CD62E+) and platelet-derived (CD61+, CD41+, CD42a+, PAC1+), red blood cell-derived (GlyA+) and leukocyte-derived (CD45+, CD13+, CD14+, CD56+) MPs were measured. Flow cytometry (FC) was performed on Beckman Coulter FC500 analyzer. MP reference gate was set using 0.3–0.5–0.9 µm microbeads with MP size gates of 0.5–1.0 µm.ResultsAll the measured MPs were significantly (P<0.001) higher in COPD patients than in the controls. Furthermore, CD62E+, CD41+, CD42a+ and CD14+ MP values were significantly (P<0.001) increased in exacerbated COPD compared to stable COPD. These MPs showed significant (P<0.001) inverse correlation with FEV1/FVC, as well.ConclusionIn this study, we describe a reliable flow cytometric assay for MP analysis that was successfully applied in COPD. Besides EMPs, COPD is accompanied by an increased concentration of various MPs in the systemic circulation; particularly, platelet- and monocyte-derived MPs seem to be important in exacerbation.

Acute effects of haemodialysis on circulating microparticles.

BackgroundMicroparticles (MPs) are small cell membrane-derived vesicles regarded as both biomarkers and mediators of biological effects. Elevated levels of MPs have previously been associated with endothelial dysfunction and predict cardiovascular death in patients with end-stage renal disease. The objective of this study was to measure change in MP concentrations in contemporary haemodialysis (HD).MethodsBlood was sampled from 20 consecutive HD patients before and 1 h into the HD session. MPs were measured by flow cytometry and phenotyped based on surface markers.ResultsConcentrations of platelet (CD41+) (P = 0.039), endothelial (CD62E+) (P = 0.004) and monocyte-derived MPs (CD14+) (P < 0.001) significantly increased during HD. Similarly, endothelial- (P = 0.007) and monocyte-derived MPs (P = 0.001) expressing tissue factor (TF) significantly increased as well as MPs expressing Klotho (P = 0.003) and receptor for advanced glycation end products (RAGE) (P = 0.009). Furthermore, MPs expressing platelet activation markers P-selectin (P = 0.009) and CD40L (P = 0.045) also significantly increased. The increase of endothelial (P = 0.034), monocyte (P = 0.014) and RAGE+ MPs (P = 0.032) as well as TF+ platelet-derived MPs (P = 0.043) was significantly higher in patients treated with low-flux compared with high-flux dialysers.ConclusionDialysis triggers release of MPs of various origins with marked differences between high-flux and low-flux dialysers. The MPs carry surface molecules that could possibly influence coagulation, inflammation, oxidative stress and endothelial dysfunction. The clinical impact of these findings remains to be established in future studies.

The effect of a short-term low-carbohydrate, high-fat diet with or without postmeal walks on glycemic control and inflammation in type 2 diabetes: a randomized trial.

Lowering carbohydrate consumption effectively lowers glucose, but impacts on inflammation are unclear. The objectives of this study were to: 1) determine whether reducing hyperglycemia by following a low-carbohydrate, high-fat (LC) diet could lower markers of innate immune cell activation in type 2 diabetes (T2D) and 2) examine if the combination of an LC diet with strategically timed postmeal walking was superior to an LC diet alone. Participants with T2D ( n = 11) completed a randomized crossover study involving three 4-day diet interventions: 1) low-fat low-glycemic index (GL), 2) and 3) LC with 15-min postmeal walks (LC+Ex). Four-day mean glucose was significantly lower in the LC+Ex group as compared with LC (-5%, P < 0.05), whereas both LC+Ex (-16%, P < 0.001) and LC (-12%, P < 0.001) conditions were lower than GL. A significant main effect of time was observed for peripheral blood mononuclear cells phosphorylated c-Jun N-terminal kinase ( P < 0.001), with decreases in all three conditions (GL: -32%, LC: -45%, and LC+Ex: -44%). A significant condition by time interaction was observed for monocyte microparticles ( P = 0.040) with a significant decrease in GL (-76%, P = 0.035) and a tendency for a reduction in LC (-70%, P = 0.064), whereas there was no significant change in LC+Ex (0.5%, P = 0.990). Both LC (-27%, P = 0.001) and LC+Ex (-35%, P = 0.005) also led to significant reductions in circulating proinsulin. An LC diet improved 4-day glycemic control and fasting proinsulin levels when compared with GL, with added glucose-lowering benefits when LC was combined with postmeal walking.

P1919Circulating monocyte-derived (CD14+) and apoptotic (annexin V-binding) microparticles correlate with recurrent atrial fibrillation

P1919Circulating monocyte-derived (CD14+) and apoptotic (annexin V-binding) microparticles correlate with recurrent atrial fibrillation

Factors Involved in Maintaining Haemostasis in Patients with Myelodysplastic Syndrome.

Etiopathogenesis of myelodysplastic syndrome (MDS) might cause per se an anomalous haemostasis that can be even more deteriorated by thrombocytopaenia. So, evaluation of haemostasis in patients with MDS rises as a necessity.This work aimed to characterize haemostasis in non-bleeder MDS patients with a platelet count similar to healthy controls to establish differences between the two groups not related to thrombocytopaenia.Thromboelastometry in samples from MDS patients suggested the existence of at least two antagonistic processes: one of them giving a hypocoagulable pattern (prolonged clotting time and lower α angle) and another conferring a procoagulant profile (decreased fibrinolysis). Hypocoagulable state might be due to a decreased ability of platelets to be stimulated and to the presence in plasma of a factor/s that prolonged the time to initiate thrombin generation. This factor/s might be antibodies as this effect was observed in samples from MDS patients with an associated autoimmune-inflammatory condition.Otherwise, hypercoagulable state seemed to rely on an increased presence of red cell- and monocyte-derived microparticles and to the increased exposure of phosphatidylserine that served as scaffold for binding of coagulation factors.We concluded that haemostasis in MDS patients is a complex process influenced by more factors than platelet count.