Levels Of Endothelial Microparticles Research Articles

SAT0212 Circulating Endothelial Microparticles Reflect Microvascular Impairment in Patients with Systemic Sclerosis

BackgroundEndothelial injury plays a key role in the pathogenesis of systemic sclerosis (SSc), but its quantitative assessment has yet to be established clinically. Circulating endothelial microparticles (EMPs) are considered markers...

Circulating endothelial microparticles (EMP) modifications as predictive biomarkers of resistance to chemotherapy for breast cancer (BC).

3042 Background: Growing evidence indicates that EMP may both modulate angiogenesis and endothelial injury in cancer and cardiovascular disease. However, it has not been shown whether in vivo release of EMP might reflect the tumor response or the antiangiogenic effects of chemotherapy (CT). The aim of this work was to evaluate the relationship between the levels of small-size EMP (sEMP) and resistance to CT in locally advanced and metastatic BC. Methods: Citrated platelet-free plasma was obtained from BC patients before and after 3-4 cycles of chemotherapy. Small-size CD144+ sEMP (0.1-0.5 μm diameter) were prospectively quantified using a high resolution Apogee A50 flow cytometer. Association of EMP with clinical variables, response to CT and survival was analyzed. Response (partial or complete) was defined by RECIST criteria. Results: 45 BC patients were included (20, metastatic; 25, locally advanced). Treatment included anthracyclines in 66.7% of patients and taxanes in 15.5%. Small-size EMP baseline counts were higher in premenopausal women (p=0.008), but no association with other clinical or pathological characteristic was found. A significant decrease of circulating sEMP was observed after treatment with CT in the whole group of patients with paired samples available (n=33): pre-CT: 416.2 ± 365 vs. post-CT: 340.7 ± 458 (p=0.005). Lower chemotherapy-induced sEMP decrease was associated to treatment resistance: ROC analysis demonstrated a 66.7% sensitivity and 72.2% specificity of lower sEMP decrease for lack of response to CT using a decline cut-point of -40 sEMP (close to median decrease: -47). With the same cut-point of low sEMP decrease, odds ratio for treatment resistance was 5.2 (95% confidence interval, 1.17-23.04; p=0.03). No clear association of the degree of sEMP decrease was found for disease or progression free survival in the neoadjuvant or in the metastatic setting. Conclusions: This study suggests that circulating sEMP decrease after CT and are tightly associated with treatment resistance in BC patients. These findings indicate pathophysiological roles for sEMP in BC and support their potential role as treatment resistance biomarkers.

Endothelial dysfunction in patients with type 2 diabetes post acute coronary syndrome

This single visit study examined whether endothelial function, in addition to cardiovascular (CV) risk factors and plasma microparticle content, was normalised in 15 patients with type 2 diabetes + acute coronary syndrome (ACS) (6 weeks-6 months post cardiac event) undergoing standard clinical care compared to 16 sex- and age-matched healthy controls. While total and low-density lipoprotein (LDL) cholesterol levels were well controlled in the patients with type 2 diabetes + ACS, residual CV risk profiles such as increased body mass index (BMI), systolic blood pressure, glucose levels and triglycerides and lower high-density lipoprotein (HDL) levels were still apparent. Endothelium-dependent responses to acetylcholine (ACh) were significantly lower in type 2 diabetes + ACS patients compared to controls. Correspondingly, the reactive hyperaemic index (RHI) was lower in the patient cohort. Endothelial microparticle (EMP) levels (CD31(+), CD41(-)) were 40% lower in the patient cohort. Simultaneous analysis of platelet microparticle (PMP) levels (CD41(+)) showed no difference between cohorts. Patients with type 2 diabetes suffering from recent ACS exhibit residual CV risk factors despite being on standard clinical care. In addition, these patients continue to present with endothelial dysfunction despite having lower levels of EMPs.

Plasma endothelial microparticles, TNF-α and IL-6 in Kawasaki disease

We studied the levels of endothelial microparticles (EMPs), IL-6, and TNF-a in patients with Kawasaki disease (KD). EMPs were enumerated by flow cytometry, while IL-6 and TNF-a were measured using enzyme-linked immunosorbent assay. EMPs and IL-6 were elevated in KD, the level of TNF-a in KD was not different from disease controls, but higher than healthy controls. EMPs were positively correlated with TNF-a and negatively correlated with albumin. Elevated level of EMPs, a biomarker of endothelial cells damage, concomitant with increased levels of TNF-a and IL-6, is seen in patients with KD.

Five days of reduced physical activity selectively impairs endothelial function of the inactive limbs

Chronic physical inactivity promotes the development of cardiovascular diseases. However, few data exist on the effects of short‐term reductions in daily ambulatory activity on vascular function, particularly at the cellular level. Thus, we studied popliteal and brachial artery flow mediated dilation (FMD) and measured plasma levels of endothelial microparticles (EMPs) shed from apoptotic and activated endothelial cells (CD31+/CD42b− and CD62E+ EMPs, respectively) at baseline and following 5 days of reduced daily steps (<5,000 steps/day) in 6 healthy, recreationally active men (26±3 yrs). We hypothesized that popliteal FMD would be reduced and concentrations of EMPs would be increased with inactivity. Following inactivity, popliteal FMD decreased (baseline: 5.4±1.2 vs. inactivity: 1.9±1.0%, p=0.05), while brachial artery FMD was unchanged (baseline: 4.2±0.7 vs. inactivity: 5.6±1.0%, p=0.12). CD31+/CD42b− (1.3 ± 0.4 vs. 4.8 ± 2.7 per μL plasma) and CD62E+ (69.2 ± 52.0 vs. 14.7 ± 7.9 per μL plasma) EMPs were not significantly altered following inactivity. These preliminary findings suggest that the vascular consequences of reduced daily steps are primarily localized to the lower (inactive) limbs, although changes in systemic EMPs reflective of endothelial apoptosis (CD31+/CD42b− ) and activation (CD62E+) were not observed.Grants: AHA 12PRE12080242, NIH R01‐HL093167, T32‐AR048523

Increased Carotid Intima-Media Thickness and Reduced Distensibility in Human Class III Obesity: Independent and Differential Influences of Adiposity and Blood Pressure on the Vasculature

Carotid intima-media-thickness (cIMT) and carotid distensibility (distensibility), structural and functional properties of carotid arteries respectively, are early markers, as well as strong predictors of cardiovascular disease (CVD). The characteristic of these two parameters in individuals with BMI>40.0 kg/m2 (Class III obesity), however, are largely unknown. The present study was designed to document cIMT and distensibility in this population and to relate these to other factors with established association with CVD in obesity. The study included 96 subjects (65 with BMI>40.0 kg/m2 and 31, age- and gender-matched, with BMI of 18.5 to 30.0 kg/m2). cIMT and distensibility were measured by non-invasive high resolution ultrasonography, circulatory CD133+/KDR+ angiogenic cells and endothelial microparticles (EMP) by flow cytometry, and plasma levels of adipokines, growth factors and cytokines by Luminex immunoassay kits. The study results demonstrated increased cIMT (0.62±0.11 mm vs. 0.54±0.08 mm, P = 0.0002) and reduced distensibility (22.52±10.79 10−3kpa−1 vs. 29.91±12.37 10−3kpa−1, P<0.05) in individuals with BMI>40.0 kg/m2. Both cIMT and distensibility were significantly associated with traditional CVD risk factors, adiposity/adipokines and inflammatory markers but had no association with circulating angiogenic cells. We also demonstrated, for the first time, elevated plasma EMP levels in individuals with BMI>40.0 kg/m2. In conclusion, cIMT is increased and distensibility reduced in Class III obesity with the changes predominantly related to conventional CVD risk factors present in this condition, demonstrating that both cIMT and distensibility remain as CVD markers in Class III obesity.

Endothelial microparticle release is stimulated in vitro by purified IgG from patients with the antiphospholipid syndrome

IgG antiphospholipid antibodies (aPL) exert direct effects on various cell types, contributing to the pathogenesis of thrombosis and pregnancy morbidity in patients with the antiphospholipid syndrome (APS). Some IgG samples from these patients activate endothelial cells (EC) in vitro as judged by surface expression of adhesion molecules such as E-selectin, which can promote thrombosis. Endothelial microparticles (EMP), which themselves are potentially prothrombotic, are released by activated EC. Though elevated circulating EMP levels have been reported in patients with APS, it is not known whether these EMP are released due to a direct effect of aPL on the cells. We tested the effect of purified polyclonal IgG from patients with APS (APS-IgG) and healthy controls (HC-IgG) upon cultured human umbilical vein EC (HUVEC). HUVEC exposed to APS-IgG produced significantly more EMP than those exposed to HC-IgG (p=0.0036) and a greater proportion of these EMP carried surface E-selectin (6.2% ± 4.0 for APS-IgG vs. 3.4% ± 2.0 for HC IgG, p=0.0172). This study therefore demonstrates that purified polyclonal APS-IgG can drive EMP release. We propose that EMP generation may be a useful measure of aPL-mediated pathogenic effects upon EC.

Small platelet microparticle levels are increased in pulmonary arterial hypertension

The various aetiologies and risk factors for pulmonary arterial hypertension (PAH) lead to close phenotypes with small differences. Plasma microparticles have been shown to be increased in vascular pathologies including PAH. The aim of this study was to determine whether the levels of endothelial and platelet-derived microparticles could vary between different forms of PAH: idiopathic PAH (iPAH), heritable PAH associated with BMPR2 (Bone morphogenetic protein receptor, type II) mutation (hPAH) and PAH associated with connective tissue diseases (aPAH). Microparticles were analysed using flow cytometry in plasma from controls and iPAH, hPAH and aPAH patients. Platelet-derived MP (PMP) were defined as CD31(+)/CD41(+) and endothelial-derived MP (EMP) as CD31(+)/CD41(-). Two populations of PMP were isolated according to their size, defining small PMP (0·3-0·5 μm) and large PMP (0·5-0·9 μm). BMPR2 genotype, clinical and biologic parameters were recorded. EMP and small PMP levels in iPAH, hPAH and aPAH were similar and were significantly increased as compared with controls. No differences in large PMP levels were observed. After adjusting for age, sex, proBNP and CRP, EMP and small PMP levels did not correlate with clinical parameters. iPAH, hPAH and aPAH were characterized by increased levels of EMP and of small PMP, a new class of PMP which seems to be differentially produced than large PMP.

Cooperation between β‐ and γ‐cytoplasmic actins in the mechanical regulation of endothelial microparticle formation

Elevated endothelial microparticle (MP) levels are observed in numerous diseases, increasingly supporting roles as effectors and valuable markers of vascular dysfunction. While a contractile role for the actin cytoskeleton has been implicated in vesiculation, i.e., MP production, the precise interactions and mechanisms of its constituents, β- and γ-cytoplasmic actins, is unknown. Human cerebral microvascular endothelial cells were stimulated with known agonists, and vesiculation development was monitored by scanning electron microscopy (SEM) and flow cytometry. These data in combination provide new insight into the kinetics, patterns of vesiculating cell recruitment, and degrees of response specific to stimuli. Reorganization of β- and γ-actins, F-actin, vinculin, and talin accompanied significant MP release. β-Actin redistribution into basal stress fibers following stimulation was associated with increased apically situated actin-rich particulate structures, which in turn directly correlated with electron-lucent membrane protrusions observed by SEM. Y-27632 Rho-kinase inhibition abolished basal β-actin fiber formation, minimizing apically associated actin-rich structures, significantly reducing membrane protrusions and MP release to near basal levels. Cytoskeletal protein expression and distribution varied between MPs and mother cells, as determined by Western blot. These data strongly suggest that β-actin plays an active facilitative role in agonist-induced protuberance formation, through mechanical interactions with newly described actin-rich structures.

Elevated Levels of Endothelial Cell-Derived Microparticles following Short-Term Withdrawal of Continuous Positive Airway Pressure in Patients with Obstructive Sleep Apnea: Data from a Randomized Controlled Trial

Background: Obstructive sleep apnea has been associated with impaired endothelial function; however, the mechanisms underlying this association are not completely understood. Cell-derived microparticles may provide a link between obstructive sleep apnea and endothelial dysfunction. Objectives: This randomized controlled trial aimed to examine the effect of a 2-week withdrawal of continuous positive airway pressure (CPAP) therapy on levels of circulating microparticles. Methods: Forty-one obstructive sleep apnea patients established on CPAP treatment were randomized to either CPAP withdrawal (subtherapeutic CPAP) or continuing therapeutic CPAP, for 2 weeks. Polysomnography was performed and circulating levels of microparticles were analyzed by flow cytometry at baseline and 2 weeks. Results: CPAP withdrawal led to a recurrence of obstructive sleep apnea. Levels of CD62E+ endothelium-derived microparticles increased significantly in the CPAP withdrawal group compared to the continuing therapeutic CPAP group (median difference in change +32.4 per µl; 95% CI +7.3 to +64.1 per µl, p = 0.010). CPAP withdrawal was not associated with a statistically significant increase in granulocyte, leukocyte, and platelet-derived microparticles when compared with therapeutic CPAP. Conclusions: Short-term withdrawal of CPAP therapy leads to a significant increase in endothelium-derived microparticles, suggesting that microparticle formation may be causally linked to obstructive sleep apnea and may promote endothelial activation.

Elevated Plasma Endothelial Microparticles in Alzheimer’s Disease

Background/Aims: Endothelial microparticles (EMPs) in plasma are elevated in several vascular diseases. Alzheimer’s disease (AD) is associated with microcirculatory injury, capillary blocking and disruption of the blood-brain barrier. We wanted to test the hypothesis that EMPs would be increased in AD patients and would correlate with a cognitive decline, and to determine if EMPs are released as a result of activation or apoptosis/necrosis in AD. Methods: EMP levels in plasma of AD patients and controls were quantified by flow cytometry. EMP markers for apoptosis/necrosis [platelet/endothelial cell adhesion molecule-1 (PECAM-1)/CD31] and for activation (E-selectin/CD62e) were evaluated. The EMP CD62E/CD31 populations ratio of ≤1.0 was used to differentiate activation from apoptosis. Results: Significantly higher CD31+/CD42– and CD62e+/CD42– counts were observed in the AD group relative to the controls (p < 0.05). There was no difference between the moderate- to-severe AD group and the mild AD group. Significant correlations were found between circulating EMP counts and Mini-Mental State Examination and AD Assessment cognition (ADAS-cog) score. Multivariate regression analysis demonstrated the persistence of significant correlations between ADAS-cog score and CD31+/CD42– EMPs. Conclusion: The (PECAM-1)/CD31 ratio demonstrated that EMPs were generated via apoptosis/necrosis and not by activation. Certain circulating EMP phenotypes may be associated with a cognitive decline of AD patients. EMP analysis shows a promising contribution to understanding vascular pathophysiology in AD.

Increased circulating endothelial microparticles in COPD patients: a potential biomarker for COPD exacerbation susceptibility

RationaleThe influence of COPD exacerbation on the endothelium is not completely understood. Circulating endothelial microparticles (EMPs) are membrane vesicles in circulating blood that are shed by activated or apoptotic endothelial...

Endothelial microparticles and the antiangiogenic state in preeclampsia and the postpartum period

We sought to determine if endothelial microparticles (EMPs), markers of endothelial damage, are associated with soluble fms-like tyrosine kinase 1 (sFlt1), soluble endoglin, and placental growth factor (PlGF) in women with preeclampsia. A prospective cohort study was conducted on 20 preeclamptic women and 20 controls. EMPs by flow cytometry, sFlt1, soluble endoglin, and PlGF were measured at time of enrollment, 48-hours postpartum, and 1-week postpartum. Preeclamptic CD31(+)/42(-), CD62E(+), and CD105(+) EMP levels were significantly elevated in preeclamptics vs controls at time of enrollment. The sFlt1:PlGF ratio was correlated with CD31(+)/42(-) and CD105(+) EMPs (r = 0.69 and r = 0.51, respectively) in preeclampsia. Levels of CD31(+)/42(-) EMPs remained elevated 1-week postpartum (P = .026). EMPs are elevated in preeclampsia. The correlation of EMPs and the sFlt1:PlGF ratio suggests that antiangiogenesis is related to apoptosis of the endothelia. Endothelial damage persists 1 week after delivery.

Arterial Erectile Dysfunction: Reliability of Penile Doppler Evaluation Integrated With Serum Concentrations of Late Endothelial Progenitor Cells and Endothelial Microparticles

We recently showed the diagnostic value of a new immunophenotype of blood endothelial progenitor cells (EPC) (CD45(-)/CD34(+)/CD144(+)) and endothelial microparticles (EMP) (CD45(-)/CD144(+)/annexin V(+)) in patients with arterial erectile dysfunction (AED), particularly in patients with associated late-onset hypogonadism and/or metabolic syndrome. In addition, we evaluated the effects of androgen replacement therapy, aerobic physical activity, and tadalafil administration on these markers. The aim of this study was to evaluate the serum concentrations of EPCs and EMPs in a large cohort of patients with AED according to severity of cavernous arterial insufficiency evaluated by penile Doppler. A total of 120 patients (aged 58.0 ± 6.0 years) with AED were enrolled in this study. Patients were classified into 3 groups based on value of peak systolic velocity (PSV). Group A: 37 patients with PSV <25 cm/s (severe arterial insufficiency); group B: 40 patients with PSV between 25 and 29 cm/s (moderate arterial insufficiency); group C: 43 patients with PSV between 30 and 34 cm/s (mild arterial insufficiency). Twenty patients (aged 60.0 ± 3.0 years) with psychogenic erectile dysfunction (PED) represented the control group. EPC and EMP blood concentrations were evaluated by flow cytometry. Patients with AED had significantly higher blood pressure, triglyceride levels, homeostasis model assessment index of insulin resistance, cavernous artery acceleration time, and intima-media thickness than those with PED, whereas International Index of Erectile Function score, high-density lipoprotein cholesterol level, and cavernous artery PSV were lower than those in PED. Both EPC and EMP levels were significantly higher in patients with AED compared with patients with PED. Among 3 groups of patients with AED, there were no significant differences in metabolic parameters examined, but group A showed significantly higher values of cavernous artery acceleration time and intima-media thickness than group B and group C. Finally, group A showed serum concentrations of EPCs and EMPs significantly higher compared with other groups with AED. Patients with AED showed worse metabolic parameters, cavernous artery parameters, and EPC and EMP levels compared with patients with PED. Among patients with AED, those with PSV <25 cm/s showed worse findings of endothelial dysfunction. This suggests that AED is an expression of endothelial damage and that this original immunophenotype of EPCs and EMPs may be considered a predictor of endothelial dysfunction in patients with AED. Finally, this study confirmed the reliability of penile Doppler evaluation integrated with these serum markers of endothelial dysfunction.

Circulating CD62E+ Microparticles and Cardiovascular Outcomes

BackgroundActivated endothelial cells release plasma membrane submicron vesicles expressing CD62E (E-selectin) into blood, known as endothelial microparticles (EMPs). We studied whether the levels of endothelial microparticles expressing CD62E+, CD31+/Annexin-V+, or CD31+/CD42− predict cardiovascular outcomes in patients with stroke history.Methods/Principal FindingsPatients with stroke history at least 3 months prior to enrolment were recruited. Peripheral blood EMP levels were measured by flow cytometry. Major cardiovascular events and death were monitored for 36 months. Three hundred patients were enrolled, of which 298 completed the study according to protocol. Major cardiovascular events occurred in 29 patients (9.7%). Nine patients died, five from cardiovascular causes. Cumulative event-free survival rates were lower in patients with high levels of CD62E+ microparticles. Multivariate Cox regression analysis adjusted for cardiovascular risk factors, medications and stroke etiologic groups showed an association between a high CD62E+ microparticle level and a risk of major cardiovascular events and hospitalization. Levels of other kinds of EMPs expressing CD31+/Annexin-V+ or CD31+/CD42− markers were not predictive of cardiovascular outcomes.ConclusionA high level of CD62E+ microparticles is associated with cardiovascular events in patients with stroke history, suggesting that the systemic endothelial activation increases the risk for cardiovascular morbidities.

Changes of endothelial microparticles in children with Kawasaki disease and its relation to coronary artery lesions

Objective To study the changes of plasma endothelial microparticles (EMP) in children with Kawasaki disease (KD) and its relation to coronary artery lesions (CAL).Methods The participants in this study were 30 children with KD (24 children with typical KD and 6 cases with incomplete KD).All KD patients met the diagnostic criteria established by the Japanese Kawasaki Disease Research Committee.According to the course of KD,3 phases were divided:the acute phase,the subacute phase and the convalescent phase.We evaluated the presence of CAL using two-dimensional echocardiographic examination,and then the KD children were divided into two groups,including 24 children without CAL and 6 children with CAL.Ten children with fever and rash and 10 healthy children were studied as control.The levels of CD31+/CD42b- EMP were measured by flow cytometry.Results The level of EMP was significantly higher in the acute phase [ (8.18 ± 2.29) ％ ] than those either in the convalescent phase [ (2.77 ± 0.85 ) ％ ] of KD or the healthy children [ ( 1.34 ± 0.38 ) ％ ] (P ＜ 0.01 ).The level of EMP was also significantly higher in the subacute phase [ (5.93 ± 1.05 )％ ] than those either in the convalescent phase of KD or the healthy children (P ＜0.01 ).The level of EMP was higher in the children with fever [ (3.66 ± 1.16) ％ ] than that in the healthy children ( P ＜ 0.05 ).Furthermore,the level of EMP during the acute phase was also higher in KD patients with CAL than in those without CAL(P ＜0.01 ).Conclusion The measurement of EMP may be useful for the early diagnosis of KD and the identification of CAL. Key words: Kawasaki disease; Endothelial microparticle; Flow cytometry; Coronary artery lesions

Association between vascular access failure and microparticles in hemodialysis patients

BackgroundVascular access failure, a major cause of morbidity in hemodialysis (HD) patients, occurs mainly at stenotic endothelium following an acute thrombotic event. Microparticles (MPs) are fragments derived from injured cell membrane and are closely associated with coagulation and vascular inflammatory responses.MethodsWe investigated the relationship between levels of circulating MPs and vascular access patency in HD patients. A total of 82 HD patients and 28 healthy patients were enrolled. We used flow cytometry to measure endothelial MPs (EMPs) identified by CD31+CD42− or CD51+ and platelet-derived MPs (PMPs) identified by CD31+CD42+ in plasma samples of participants. Vascular access patency was defined as an interval from the time of access formation to the time of first access stenosis in each patient. MP counts were compared according to access patent duration.ResultsThe levels of EMP (both CD31+CD42− and CD51+) and CD31+CD42+PMP were significantly higher in patients than in healthy participants. Levels of CD31+CD42−EMP and CD31+CD42+PMP showed a positive correlation. In non-diabetic HD patients, CD31+CD42−EMPs and CD31+CD42+PMPs were more elevated in the shorter access survival group (access survival <1 year) than in the longer survival group (access survival ≥ 4 years).ConclusionElevated circulating EMP or PMP counts are influenced by end-stage renal disease and increased levels of EMP and PMP may be associated with vascular access failure in HD patients.

Abstract 3713: Possible Role Of Circulating Cellular Microparticles In Progressive Hypertension And Middle Cerebral Artery Remodeling

Circulating cellular microparticles (MPs) are potential biomarkers for cardiovascular diseases and are also suggested to be involved in the pathogenesis of hypertension and stroke. We assessed the hypothesis that circulating MPs could have implications in influencing mean arterial pressure (MAP) and middle cerebral artery (MCA) remodeling via changes in their levels and contents. Male C57BL/6 mice were fed with normal diet (control) or induced to progressive hypertension by infusion with angiotensin II (ANG II, 42µg/kg/h, osmotic minipump) and fed with high-salt diet (HSD, 8% NaCl) plus L-NAME (120 mg/kg/day, in drinking water) for 2 (for MPs donor) and 4 weeks (for MP infusion study). Circulating MPs isolated from control (cMPs) or hypertensive (hMPs) mice were isolated as we previously described (Chen, et al, AJP, 2011). The levels of circulating endothelial MPs (EMPs) and endothelial progenitor cells-MPs (EPC-MPs) were analyzed using flow cytometry by staining with CD144 (EMPs), CD34 and VEGFR2 (EPC-MPs), respectively. The mRNA levels of CXCR4, endothelial nitric oxide synthase (eNOS), NOX2 and tumor necrosis factor-alpha (TNF-a) in circulating MPs were determined by quantitative real-time RT-PCR. In separate experiment, control or hypertensive mice were treated with infusion of cMPs or hMPs (1x10 5 /100µl) via tail vein once per week for two continuous weeks, and sacrificed at the end of experiment (week four). MAP was measured using radiotelemetric probe. The lumen/wall in the MCA was determined by Hematoxylin and Eosin staining. Results showed ( table ): 1) Mice infused with ANG II and fed with HSD and L-NAME showed progressive hypertension and MCA remodeling. 2) The levels of EMP and EPC-MPs were significantly increased in hypertensive mice. 3) hMPs carried less CXCR4 and eNOS, and higher NOX2 and TNF-a mRNAs when compared with cMPs. 4) Infusion of hMPs increased MAP and MCA remodeling in hypertensive mice, but only induced MCA remodeling in control mice. 5) cMPs decreased MAP and MCA in hypertensive mice, but had no effect on MCA remodeling and MAP in control mice. In conclusion, circulating MPs could be served as biomarkers and used for developing therapeutic avenues for progressive hypertensive and MCA remodeling.

Increased endothelial microparticles in obese and overweight children

Obesity in children increases the risk of atherosclerosis. Endothelial dysfunction is an important factor in the pathogenesis of atherosclerosis, and endothelial microparticles (EMPs) are considered as markers of endothelial dysfunction. In this study, we aimed to evaluate circulating EMPs in obese and overweight children and to disclose the measure of obesity with the strongest relation with circulating microparticles and carotid atherosclerosis. This prospective study included 55 obese and overweight children and 23 healthy controls. Insulin resistance was studied. Both in vivo and in vitro human umbilical vein endothelial cell evaluations were used for the study. Circulating EMPs (CD144 and CD146) were measured by flow cytometry. The carotid artery intima-media thickness (cIMT) and left ventricular mass index (LVMI) were measured using ultrasound and echocardiography, respectively. Study groups were compared for anthropometric measurement, insulin resistance, circulating EMP, cIMT, and LVMI. The relationship among overweight, obesity, and circulating EMPs were investigated. Blood pressure, CD144+EMP levels, and LVMI were statistically higher in the patients group than in the control group. The multiple logistic regression analysis and the backward elimination method showed that CD144+EMP and systolic blood pressure had a linear relationship with overweight and obesity. Our results suggest that endothelial damage starts in the early stage of childhood obesity and that obese and overweight children have increased circulating CD144+EMPs, showing that endothelial dysfunction and increased CD144+EMPs may be related to obesity.

Limited Cutaneous and Diffuse Cutaneous Scleroderma: Circulating Biomarkers Differentiate Lung Involvement

Study background: Insufficient or absent angiogenesis are hallmarks of scleroderma (SSc). Microvascular change is an early manifestation of SSc followed by intimal proliferation and fibrosis of arterioles resulting in reduced blood flow and tissue ischemia. This ongoing vasculopathy in the lungs presents clinically as pulmonary hypertension and characteristically precedes lung fibrosis in patients. The purpose of this preliminary study is to elucidate possible interrelationships amongst circulating microparticles, angiogenic and angiostatic factors in SSc patients that are predictive of interstitial lung disease and high values of right ventricular systolic pressure (RVSP) by trans-thoracic Doppler-echocardiography (TTE). Methods: Nineteen cases with limited cutaneous SSc (lcSSc) and 11 cases with diffuse cutaneous SSc (dcSSc) were compared to 30 age- and sex-matched healthy controls. High resolution computed tomography was used to establish the diagnosis of interstitial lung disease and TTE was used to estimate RVSP and to diagnose putative pulmonary arterial hypertension (PAH). Plasma concentrations of circulating factors were assessed in patients and controls. Results: Angiopoetin-2, endostatin, E-selectin and platelet microparticles were higher in lcSSc cases compared to healthy controls (p<0.0001, p=0.0008, p=0.0003, p=0.0020, respectively). Only endostatin was higher in dcSSc cases (p=0.0020). In a classification tree analysis, concentrations of soluble E-selectin of at least 44.7 ng/ml and 37.2 ng/ml were predictive of ILD and PAH, respectively, in lcSSc cases, whereas, endothelial microparticle levels higher than 96 per μl were predictive of ILD in dcSSc cases. Conclusion: Scleroderma cases can be differentiated from healthy controls based on higher concentrations of the angiostatic factor endostatin. E-selectin was associated with lung involvement in lcSSc, whereas, high levels of endothelial microparticles were associated with ILD in dcSSc.