Endothelial Microparticles Research Articles

Biogenesis of Pro-senescent Microparticles by Endothelial Colony Forming Cells from Premature Neonates is driven by SIRT1-Dependent Epigenetic Regulation of MKK6

Senescent cells may exert detrimental effect on microenvironment through the secretion of soluble factors and the release of extracellular vesicles, such as microparticles, key actors in ageing and cardiovascular diseases. We previously reported that sirtuin-1 (SIRT1) deficiency drives accelerated senescence and dysfunction of endothelial colony-forming cells (ECFC) in PT neonates. Because preterm birth (PT) increases the risk for cardiovascular diseases during neonatal period as well as at adulthood, we hypothesized that SIRT1 deficiency could control the biogenesis of microparticles as part of a senescence–associated secretory phenotype (SASP) of PT-ECFC and investigated the related molecular mechanisms. Compared to control ECFC, PT-ECFC displayed a SASP associated with increased release of endothelial microparticles (EMP), mediating a paracrine induction of senescence in naïve endothelial cells. SIRT1 level inversely correlated with EMP release and drives PT-ECFC vesiculation. Global transcriptomic analysis revealed changes in stress response pathways, specifically the MAPK pathway. We delineate a new epigenetic mechanism by which SIRT1 deficiency regulates MKK6/p38MAPK/Hsp27 pathway to promote EMP biogenesis in senescent ECFC. These findings deepen our understanding of the role of ECFC senescence in the disruption of endothelial homeostasis and provide potential new targets towards the control of cardiovascular risk in individuals born preterm.

Nanobubbles Form at Active Hydrophobic Spots on the Luminal Aspect of Blood Vessels: Consequences for Decompression Illness in Diving and Possible Implications for Autoimmune Disease-An Overview.

Decompression illness (DCI) occurs following a reduction in ambient pressure. Decompression bubbles can expand and develop only from pre-existing gas micronuclei. The different hypotheses hitherto proposed regarding the nucleation and stabilization of gas micronuclei have never been validated. It is known that nanobubbles form spontaneously when a smooth hydrophobic surface is submerged in water containing dissolved gas. These nanobubbles may be the long sought-after gas micronuclei underlying decompression bubbles and DCI. We exposed hydrophobic and hydrophilic silicon wafers under water to hyperbaric pressure. After decompression, bubbles appeared on the hydrophobic but not the hydrophilic wafers. In a further series of experiments, we placed large ovine blood vessels in a cooled high pressure chamber at 1,000 kPa for about 20 h. Bubbles evolved at definite spots in all the types of blood vessels. These bubble-producing spots stained positive for lipids, and were henceforth termed “active hydrophobic spots” (AHS). The lung surfactant dipalmitoylphosphatidylcholine (DPPC), was found both in the plasma of the sheep and at the AHS. Bubbles detached from the blood vessel in pulsatile flow after reaching a mean diameter of ~1.0 mm. Bubble expansion was bi-phasic—a slow initiation phase which peaked 45 min after decompression, followed by fast diffusion-controlled growth. Many features of decompression from diving correlate with this finding of AHS on the blood vessels. (1) Variability between bubblers and non-bubblers. (2) An age-related effect and adaptation. (3) The increased risk of DCI on a second dive. (4) Symptoms of neurologic decompression sickness. (5) Preconditioning before a dive. (6) A bi-phasic mechanism of bubble expansion. (7) Increased bubble formation with depth. (8) Endothelial injury. (9) The presence of endothelial microparticles. Finally, constant contact between nanobubbles and plasma may result in distortion of proteins and their transformation into autoantigens.

Effect of Intensive Periodontal Therapy on Blood Pressure and Endothelial Microparticles in Patients With Prehypertension and Periodontitis: A Randomized Controlled Trial.

Although some studies show a positive association between periodontitis and blood pressure (BP) elevation, research on the effect of intensive periodontal treatment on decline in BP levels and endothelial microparticles (EMPs) without any antihypertensive management is lacking. Therefore, the present clinical trial explores whether intensive periodontal therapy would lower BP levels and EMPs of patients with prehypertension with periodontitis. From a total 107 patients, 95 underwent randomization (47 assigned to control-treatment [CT] group and 48 assigned to intensive-treatment [IT] group) and completed the trial. Patients received intervention for 4 consecutive weeks and were followed for 6 months. Levels of BP and EMPs were evaluated at baseline and 1, 3, and 6 months after intervention. Periodontal conditions were significantly improved (P <0.05) 6 months after intensive periodontal treatment. In parallel, the primary outcomes including systolic and diastolic BP and EMPs were markedly reduced in the IT group compared with the CT group (absolute difference: 12.57 and 9.65 mm Hg and 581.59/μL, respectively; 95% confidence intervals: 10.45 to 14.69, 7.06 to 12.24, and 348.12 to 815.06, respectively; P <0.05). Reduction in BP levels and EMPs was related to improvement in probing depth (r = 0.358, 0.363, and 0.676, respectively, by the Pearson product-moment correlation; P = 0.009, 0.008, and P <0.001, respectively). To the best knowledge of the authors, the present study demonstrates for the first time that intensive periodontal intervention without any antihypertensive medication therapy may be an effective means to lower levels of BP and EMPs in patients with prehypertension with periodontitis.

P1762Inflammasome-induced endothelial microparticles impair cellular function in recipient cells

P1762Inflammasome-induced endothelial microparticles impair cellular function in recipient cells

P1542High intensity physical activity during marathon running increases endothelial microparticles

P1542High intensity physical activity during marathon running increases endothelial microparticles

The structure property and endothelial protective activity of fucoidan from Laminaria japonica

Four antithrombotic fucoidan fractions F1, F2, LF1, and LF2 with different monosaccharide composition, molecular weight, and degree of sulfation and sulfate position were prepared from Laminaria japonica by hot water extraction and radical degradation. Their endothelial protective activity and possible action mechanism were studied using both cell- and rat-based models systematically. By comparison, the low molecular weight (LMW) fucoidan LF1 and LF2 were more potent than the medium molecular weight (MMW) fucoidan F1 and F2 in endothelial protection, down-regulation of von Willebrand Factor, CD31 and CD51 expressing endothelial microparticles in adrenalin-induced arterial endothelial injury rats and human umbilical vein endothelial cell system. However, the highly sulfated fucoidan fractions F2 and LF2 were better at inducing FGFR1c-expressing BaF3 cell proliferation in the presence of FGF-1, -2, -7, -8, -9 or -10. These results indicated that the chemical property of fucoidan was correlated to its specific biological activity tested. Therefore, defying fucoidan’s monosaccharide composition, molecular weight, and degree of sulfation might be important in developing it into a medicine.

Abstract 203: Glucose Stimulated Endothelial Microparticles Increase Endothelial Cell Apoptotic Susceptibility

Clinical interest in endothelial cell-derived microparticles (EMPs) has increased due to their role in the pathogenesis of vascular disease. Although released by the endothelium, EMPs have autocrine properties that can significantly impact endovascular health. Hyperglycemic conditions, such as diabetes, are known to stimulate EMP release; however, the effects of these glucose-related microparticles on endothelial cell function are not well understood. High glucose concentrations induce endothelial cell apoptosis through a caspase-3-dependent mechanism. The aim of this study was to determine the effect of EMPs derived from a hyperglycemic condition on endothelial cell susceptibility to apoptosis. Human umbilical vein endothelial cells (HUVECs) were cultured (3 rd passage) and plated in 6-well plates at a density of 5.0 x 10 5 cell/condition. Cells were incubated with RPMI 1640 media containing 25mM D-glucose (concentration representing a diabetic glycemic state) or 5mM D-glucose (control, normoglycemic, condition) for 48 h to generate EMPs. EMPs derived from both conditions were pelleted by centrifugation and resuspended in culture media. EMP identification (CD144 + expression) and number was determined by flow cytometry. HUVECs (2 x10 6 cells/condition) were treated with EMPs (2:1 ratio) generated from either the hyperglycemic or normoglycemic conditions for 24 h. Thereafter, cells were treated with staurosporine (1μmol/L) for 3 h at 37°C and biotin-ZVKD-fmk inhibitor for 1 h at 37°C. Intracellular concentration of active caspase-3 was determined by enzyme immune assay. Cellular expression of miR-Let7a, an anti-apoptotic microRNA, was determined by RT-PCR using the ΔΔCT normalized to RNU6. Hyperglycemic EMPs resulted in significant increase in basal (1.5 + 0.1 vs 1.0 + 0.1 ng/mL) and staurosporine-stimulated (2.2 + 0.2 vs 1.4 + 0.1 ng/mL) caspase-3 activity compared with normoglycemic EMPs. Additional, the expression of miR-Let7a was markedly reduced (~140%) in response to hyperglycemic EMPs (0.43 + 0.17 fold vs control). These results demonstrate that hyperglycemic-induced EMPs increase endothelial cell apoptotic susceptibility. This apoptotic effect may be mediated, at least in part, by a reduction in miR-Let7a expression.

Differential Response to Exercise in African Americans with High Levels of Inflammation.

Systemic inflammation, measured by C-reactive protein (CRP), is an important risk factor for cardiovascular disease (CVD) and mortality. We investigated whether aerobic exercise training (AEXT) affects African Americans with high inflammation (HI) the same way it does African Americans with low inflammation (LI) in terms of CVD risk factors. 23 African Americans with CRP levels <3 mg/L (LI) and 14 African Americans with CRP ≥3 mg/L (HI) underwent six months of AEXT. Participants were sedentary, non-diabetic, non-smoking, with clinical blood pressure <160/100 mm Hg, were non-hyperlipidemic, had no signs of cardiovascular, renal, or pulmonary disease, and were not on medication. Measures included CD62E+ endothelial microparticles (EMPs), a measure of early stage endothelial dysfunction, as well as lipid and glucose profile, aerobic fitness, body composition, and blood pressure. The LI group improved aerobic fitness by 10%, body mass index by 3%, and plasma triglycerides by 20%, with no change being observed in HI group for these variables. The HI group improved fasting plasma glucose levels by 10%, with no change occurring in the LI group. Both groups improved CD62E+ EMPs by 38% and 59% for the LI and HI group, respectively. A standard AEXT intervention differentially affected CVD risk factors among African Americans with high and low inflammation. This may indicate that, in African Americans with high inflammation, AEXT alone may not be enough to reap the same benefits as their low-inflammation peers in terms of CVD risk modification.

MicroRNA-92a Mediates Endothelial Dysfunction in CKD.

CKD is an independent risk factor for cardiovascular disease (CVD). The accumulation of uremic toxins in CKD induces oxidative stress and endothelial dysfunction. MicroRNA-92a (miR-92a) is induced by oxidative stress in endothelial cells (ECs) and involved in angiogenesis and atherosclerosis. We investigated a role for oxidative stress-responsive miR-92a in CKD. Our study of patients at three clinical sites showed increased serum miR-92a level with decreased kidney function. In cultured ECs, human CKD serum or uremic toxins (such as indoxyl sulfate), compared with non-CKD serum, induced the levels of miR-92a and suppressed the expression of miR-92a targets, including key endothelial-protective molecules. The antioxidant N-acetylcysteine inhibited these vasculopathic properties. In rats, adenine-induced CKD associated with increased levels of miR-92a in aortas, serum, and CD144+ endothelial microparticles. Furthermore, CD144+ microparticles from human uremic serum contained more miR-92a than those from control serum. Additional analysis showed a positive correlation between serum levels of miR-92a and indoxyl sulfate in a cohort of patients with ESRD undergoing hemodialysis. Collectively, our findings suggest that the uremic toxins accumulated in CKD can upregulate miR-92a in ECs, which impairs EC function and predisposes patients to CVD.

Endothelial microparticles prevent lipid-induced endothelial damage via Akt/eNOS signaling and reduced oxidative stress.

Endothelial microparticles (EMPs) are endothelium-derived submicron vesicles that are released in response to diverse stimuli and are elevated in cardiovascular disease, which is correlated with risk factors. This study investigates the effect of EMPs on endothelial cell function and dysfunction in a model of free fatty acid (FFA) palmitate-induced oxidative stress. EMPs were generated from TNF-α-stimulated HUVECs and quantified by using flow cytometry. HUVECs were treated with and without palmitate in the presence or absence of EMPs. EMPs were found to carry functional eNOS and to protect against oxidative stress by positively regulating eNOS/Akt signaling, which restored NO production, increased superoxide dismutase and catalase, and suppressed NADPH oxidase and reactive oxygen species (ROS) production, with the involvement of NF-erythroid 2-related factor 2 and heme oxygenase-1. Conversely, under normal conditions, EMPs reduced NO release and increased ROS and redox-sensitive marker expression. In addition, functional assays using EMP-treated mouse aortic rings that were performed under homeostatic conditions demonstrated a decline in endothelium-dependent vasodilatation, but restored the functional response under lipid-induced oxidative stress. These data indicate that EMPs harbor functional eNOS and potentially play a role in the feedback loop of damage and repair during homeostasis, but are also effective in protecting against FFA-induced oxidative stress; thus, EMP function is reflected by the microenvironment.—Mahmoud, A. M., Wilkinson, F. L., McCarthy, E. M., Moreno-Martinez, D., Langford-Smith, A., Romero, M., Duarte, J., Alexander, M. Y. Endothelial microparticles prevent lipid-induced endothelial damage via Akt/eNOS signaling and reduced oxidative stress.

Curcumin and Endothelial Function: Evidence and Mechanisms of Protective Effects.

The endothelium is a large paracrine organ regulating cell growth, vascular tone and thrombogenicity as well as platelet and leukocyte interactions. Endothelial function can be assessed by noninvasive techniques [e.g. flow-mediated vasodilation, nitroglycerin-mediated dilation and pulse wave velocity] and measuring specific circulating biomarkers [cell adhesion molecules, endothelial microparticles and endothelial progenitor cells]. Impaired endothelial function plays a key role in the development of atherosclerosis, arterial hypertension, heart failure, ischemia-reperfusion injury, Alzheimer's disease and other conditions. Endothelial function is also involved in growth and proliferation of tumor cells. We performed a literature review and assessed the role of the natural polyphenol, curcumin, as a potential inexpensive, well-tolerated, and safe agent for improving endothelial function. Curcumin exerts several positive pharmacological effects; these include anti-inflammatory, antioxidant, anti-hypertensive, anti-cancer, antiviral, anti-infective and wound-healing properties. Specifically, curcumin's anti-inflammatory effects are thought to be caused by reducing trans-endothelial monocyte migration by reduction of mRNA and protein expression of intercellular adhesion molecule-1, vascular cell adhesion molecule-1 and P-selectin and by modulating NFκB, JNK, p38 and STAT-3 in endothelial cells. Dietary curcumin supplementation can also increase antioxidant activity through the induction of heme oxygenase-1, a scavenger of free radicals, and by reduction of reactive oxygen species and Nox-2. Curcumin appears to improve endothelial function but additional research is needed to determine the precise mechanism(s) and biomarkers involved in curcumin's therapeutic effects on endothelial dysfunction.

Influence of sex on the number of circulating endothelial microparticles and microRNA expression in middle‐aged adults

What is the central question of this study? Are there sex-related differences in the number of circulating endothelial microparticles (EMPs) and microparticle microRNA expression in middle-aged adult humans? What is the main finding and its importance? Although the numbers of circulating endothelial microparticles do not differ between middle-aged men and women, there are sex-related differences in the expression of miR-125a in activation-derived EMPs and miR-34a in apoptosis-derived EMPs. Differences in circulating endothelial microparticle microRNA content may provide new insight into the sex-related disparity in the risk and prevalence of vascular disease in middle-aged adults. The aims of this study were to determine: (i) whether circulating concentrations of endothelial microparticles (EMPs) differ in middle-aged men compared with women; and (ii) whether there are sex-related differences in microRNA expression in EMPs. Peripheral blood was collected from 30 sedentary adults: 15 men (56±6years old) and 15 women (56±5years old). Endothelial microparticles were defined by markers of activation (CD62e+ ) or apoptosis (CD31+ /CD42b- ) by flow cytometry. Expression of microRNA (miR-34a, 92a, 125a and 126) in activation- and apoptosis-derived EMPs was measured by RT-PCR. Circulating activation- (33±31 versus 39±35microparticlesμl-1 ) and apoptosis-derived EMPs (49±54 versus 42±43microparticlesμl-1 ) were not significantly different between men and women. Expression of miR-125a (2.23±2.01 versus 6.95±3.99a.u.) was lower (∼215%; P<0.05) in activation-derived EMPs, whereas expression of miR-34a (1.17±1.43 versus 0.38±0.35a.u.) was higher (∼210%; P<0.05) in apoptosis-derived EMPs from men compared with women. Expression of microRNA in circulating EMPs may provide new insight into sex-related differences in cardiovascular disease.

AGE-DEPENDENT INCREASE IN ENDOTHELIAL MICROPARTICLES IN HEALTHY SUBJECTS: IMPACT OF COCOA FLAVANOLS

Background: Clinical studies show that cocoa flavanols (CF) can decrease vascular stiffness and blood pressure and improve endothelial function even in healthy elderly subjects. We investigated whether age-dependent changes in circulating endothelial microparticles (EMPs) exist, whether these correlate with age-dependent vascular changes, and whether a CF-intervention also affects EMPs. Methods: EMPs were determined in 52 healthy subjects (22-75years) by flow cytometry. Endothelial function (flow-mediated-vasodilation; FMD), blood pressure, and wall-shear-stress (WSS) were measured. Using pulse-wave-analysis, pulse wave velocity (PWV) and aortic augmentation index (AIX) were measured. 22 young (<35yrs) and 20 elderly (50-80yrs) non-smoking healthy male consumed either CF-containing-drink [450mg] or nutrient-matched, CF-free-control BID for 14 days. Measurements were taken after overnight fasting before and 1h after the first drink on day 1 and day 14. Results: With increasing age, CD62e+ but not CD31+/41- and CD144+-EMPs, increased. Significant correlations were found between age and systolic blood pressure (SBP) and AIX. In elderly subjects, we observed an increased BA diameter and hence reduced WSS and FMD. CD62e+ correlated with SBP and inversely with FMD. Following 2 weeks of daily CF intake, FMD and PWV improved in young and elderly individuals. CF decreased AIX and thus SBP in elderly. CD62e+ and CD31+/41--MPs but not CD144+ significantly decreased in both groups. The decrease in CD62e+ correlated with decreases in SBP, AIX, and inversely with FMD improvements. Conclusion: In healthy humans, cardiovascular aging is associated with EMPs indicative of endothelial injury and can be modulated by dietary CFs along with improvements in vascular function.

Clinical significance of circulating microparticles in Ph- myeloproliferative neoplasms.

Microparticles (MPs) are small membrane vesicles that are classified into subcategories based on their origin, such as platelet-derived MPs (PMPs), endothelial MPs (EMPs), red blood cell MPs (RMPs) and tissue factor MPs (TF + MPs). Philadelphia chromosome-negative myeloproliferative neoplasms (Ph-MPN) are disorders characterized by abnormal haematopoiesis, thrombosis and the JAK2V617F mutation. MPs are biomarkers for procoagulant state in cancer patients, but their relevance in patients with Ph-MPN was unclear. The present study aimed to measure MP variation in MPN patients and evaluate association with the JAK2V617F mutation and with thrombosis and splenomegaly. In total, 92 patients with MPN were enrolled in the present study, including 60 with essential thrombocythaemia (ET), 20 with polycythaemia vera (PV), and 12 with primary myelofibrosis (PMF). RMPs, PMPs, TF + MPs and EMPs were measured by flow cytometry. The levels of RMPs, PMPs, EMPs and TF + MPs in patients with Ph-MPN were all found to be significantly increased compared with controls (P<0.05). Additionally, the levels of all four types of MPs in the PMF group were significantly increased compared with the PV group (P<0.05), and the level of RMPs in the PMF group was significantly increased compared with the ET group (P<0.05). MP levels were increased in the Ph-MPN patients with thrombosis compared with patients without thrombosis (P<0.05). MP levels were increased in Ph-MPN patients with splenomegaly compared with patients without splenomegaly (P<0.05). The level of PMPs in patients with the JAK2V617F mutation was increased compared with patients without the mutation (P<0.05). In conclusion, the present study showed that MPs are associated with Ph-MPN pathogenesis, and may promote thrombosis.

Effects of combination therapy of tirofiban and reteplase on endothelial function, coagulation function and inflammatory factors in elderly patients with acute ST-segment elevation myocardial infarction

Objective To investigate the effect of the combination therapy of tirofiban and reteplase on endothelial function, coagulation function and plaque inflammation in elderly patients with ST-elevation acute myocardial infarction (STEMI). Methods 100 patients with STEMI were treated with percutaneous transluminal coronary intervention (PCI) from January 2014 to June 2016 in our hospital.39 cases in the control group used conventional oral aspirin, clopidogrel and statins and other treatment.61 cases in the observation group received tirofiban and reteplase on the basis of the control group.The expression of endothelial microparticles (EMP) was detected by flow cytometry (FCM), and the ICAM-1, high sensitivity C-reactive protein (hs-CRP), tumor necrosis factor α(TNF-α) and interleukin-6 (IL-6), endothelin-1(ET-1) were measured by enzyme-linked immunosorbent assay (ELISA). The thrombin time (TT), activated partial thrombin time (APTT), prothrombin time (PT) and other indicators were measured by PUN-2048A coagulation instrument, then statistical analysis was performed. Results The postoperative levels of EMP, ICAM-1 and ET-1 of control group were (693.46±90.72), (768.58±20.46)μg/L and (31.27±8.18)ng/L, which were significantly higher than those in the observation group [(652.36±67.39), (752.37±25.0)μg/L, (28.22±5.05)ng/L], the differences were statistically significant (t=2.41, 2.67, 2.68, all P<0.05). After operation, the hs-CRP, TNF-α, IL-6 levels in the control group were (4.16±2.35)mg/L, (4.32±2.02)ng/L, (10.59±3.16)ng/mL, which were significantly higher than those in the observation group [(2.22±1.47)mg/L, (2.74±1.52)ng/L, (6.33±2.24)ng/mL], the differences were statistically significant(t=2.65, 2.67, 3.42, all P<0.05). The postoperative TT, PT, APTT in the observation group were (26.31±3.18)s, (14.34±1.67)s, (27.20±4.12)s, which were significantly longer than those in the control group [(24.03±2.84)s, (12.56±1.43)s, (24.55±3.62)s], the differences were statistically significant(t=2.15, 2.31, 2.65, all P<0.05). Conclusion Tirofiban combined with reteplase can improve endothelial function, inhibit inflammatory reaction and regulate coagulation function. Key words: Myocardial infarction; Platelet membrane glycoprotein IIb; Tirofiban hydrochloride; Reteplase

High glucose increases the formation and pro-oxidative activity of endothelial microparticles.

Individuals with diabetes exhibit increases in circulating endothelial microparticles (eMPs, also referred to as endothelial microvesicles), which are associated with endothelial dysfunction and a heightened risk of cardiovascular complications. We have shown that eMPs are markers and mediators of vascular injury although their role in diabetes is unclear. We hypothesised that the composition and biological activity of eMPs are altered in response to high glucose exposure. We assessed the effects of high glucose on eMP formation, composition and signalling in cultured HUVECs. eMPs were isolated from the media of HUVECs cultured under conditions of normal glucose (eMPNG), high glucose (eMPHG) or osmotic control of L-glucose (eMPLG). eMP size, concentration and surface charge were assessed by nanoparticle tracking analysis and flow cytometry. eMP protein composition was assessed by liquid chromatography-tandem mass spectrometry, and eMP-mediated effects on coagulation, reactive oxygen species (ROS) production and vessel function were assessed. Exposure of HUVECs to high glucose for 24h caused a threefold increase in eMP formation, increased mean particle size (269±18nm vs 226±11nm) and decreased surface charge. Compared with eMPNG or eMPLG, eMPHG possessed approximately threefold greater pro-coagulant activity, stimulated HUVEC ROS production to a greater extent (~250% of eMPNG) and were more potent inhibitors of endothelial-dependent relaxation. Proteomic analysis of eMPs identified 1212 independent proteins of which 68 were exclusively found in eMPHG. Gene ontology analysis revealed that eMPHG-exclusive proteins were associated with signalling pathways related to blood coagulation, cell signalling and immune cell activation. Our results indicate that elevated glucose is a potent stimulus for eMP formation that also alters their molecular composition leading to increased bioactivity. Such effects may contribute to progressive endothelial injury and subsequent cardiovascular complications in diabetes.

Serum Biomarkers of Erectile Dysfunction in Diabetes Mellitus: A Systematic Review of Current Literature

Erectile dysfunction (ED) is a common complication in patients with diabetes mellitus (DM). However, the utility of serum biomarkers as clinical surrogates for the development and/or progression of ED is unknown. To summarize the current literature for serum biomarkers for ED in DM and emphasize areas for future research. Human subject data demonstrating the utility of serum markers for the development and progression of ED in patients with DM. We performed a systematic PubMed-Medline search in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement using Medical Subject Headings (MeSH) for articles published from January 1, 2000 through December 31, 2016 of serum biomarkers for development or progression of ED in patients with DM using erectile dysfunction [MeSH] AND (biomarkers [MeSH] or inflammation mediators [MeSH] or intercellular signaling peptides and proteins [MeSH] or cell adhesion molecules [MeSH]). A thorough review of these studies was completed. Of the 327 abstracts screened, 12 full-text studies were assessed and 1 study was excluded. Eleven studies assessing serum biomarkers for ED in patients with DM were included in this review. The most studied serum biomarkers for ED in men with DM included endothelial dysfunction markers such as serum E-selectin, endothelial progenitor cells, and endothelial microparticles and specific markers of inflammation such as interleukin-10, ratio of tumor necrosis factor-α to interleukin-10, and reactive oxygen species such as nitric oxide and malondialdehyde. Reliable serum biomarkers will enable earlier diagnosis and objective monitoring of disease progression and responses to treatment in patients with ED. Serum biomarkers for ED in men with DM are very limited. Future longitudinal studies with uniform patient characteristics are needed to evaluate the potential clinical use of serum biomarkers in men with DM for the development and progression of ED. Patel DP, Craig JR, Myers JB, etal. Serum Biomarkers of Erectile Dysfunction in Diabetes Mellitus: A Systematic Review of Current Literature. Sex Med Rev 2017:5:339-348.

1314Endothelial progenitor cells and apoptotic endothelial cell-derived microparticle ratio predicts atrial fibrillation in chronic heart failure

1314Endothelial progenitor cells and apoptotic endothelial cell-derived microparticle ratio predicts atrial fibrillation in chronic heart failure

Passive heat stress reduces circulating endothelial and platelet microparticles.

What is the central question of this study? Does passive heat stress of +2°C oesophageal temperature change concentrations of circulating arterial endothelial- and platelet-derived microparticles in healthy adults? What is the main finding and its importance? Concentrations of circulating endothelial- and platelet-derived microparticles were markedly decreased in heat stress. Reductions in circulating microparticles might indicate favourable vascular changes associated with non-pathological hyperthermia. Interest in circulating endothelial- and platelet-derived microparticles (EMPs and PMPs, respectively) has increased because of their potential pathogenic role in vascular disease and as biomarkers for vascular health. Hyperthermia is commonly associated with a pro-inflammatory stress but might also provide vascular protection when the temperature elevation is non-pathological. Circulating microparticles might contribute to the cellular adjustments and resultant vascular impacts of hyperthermia. Here, we determined whether circulating concentrations of arterial EMPs and PMPs are altered by passive heat stress (+2°C oesophageal temperature). Ten healthy young men (age 23±3years) completed the study. Hyperthermia was achieved by circulating ∼49°C water through a water-perfused suit that covered the entire body except the hands, feet and head. Arterial (radial) blood samples were obtained immediately before heating (normothermia) and in hyperthermia. The mean±SD oesophageal temperature in normothermia was 37.2±0.1°C and in hyperthermia 39.1±0.1°C. Concentrations of circulating EMPs and PMPs were markedly decreased in hyperthermia. Activation-derived EMPs were reduced by ∼30% (mean±SD; from 61±8 to 43±7microparticlesμl-1 ; P<0.05) and apoptosis-derived EMPs by ∼45% (from 46±7 to 23±3microparticlesμl-1 ; P<0.05). Likewise, circulating PMPs were reduced by ∼75% in response to hyperthermia (from 256±43 to 62±14microparticlesμl-1 ). These beneficial reductions in circulating EMPs and PMPs in response to a 2°C increase in core temperature might partly underlie the reported vascular improvements following therapeutic bouts of physiological hyperthermia.

Parvovirus B19-induced vascular damage in the heart is associated with elevated circulating endothelial microparticles

BackgroundDiagnosis of viral myocarditis is difficult by clinical criteria but facilitated by detection of inflammation and viral genomes in endomyocardial biopsies. Parvovirus B19 (B19V) targets endothelial cells where viral nucleic acid is exclusively detected in the heart. Microparticles (MPs) are released after cell damage or activation of specific cells. We aimed to investigate whether circulating endothelial MPs (EMPs) in human and experimental models of myocarditis are associated with B19V myocarditis.MethodsMPs were investigated in patients with myocarditis (n = 54), divided into two groups: B19V+ (n = 23) and B19V- (n = 31) and compared with healthy controls (HCTR, n = 25). MPs were also investigated in B19V transgenic mice (B19V-NS1+) and mice infected with coxsackievirus B3 (CVB3). MPs were analyzed with fluorescent activated cell sorting (FACS).ResultsIn human samples, EMP subpopulation patterns were significantly different in B19V+ compared to B19V- and HCTR (p<0.001), with an increase of apoptotic but not activated EMPs. Other MPs such as platelet- (PMPs) leukocyte-(LMPs) and monocyte-derived MPs (MMPs) showed less specific patterns. Significantly different levels of EMPs were observed in transgenic B19V-NS1+ mice compared with CVB3-infected mice (p<0.001).ConclusionEMP subpopulations are different in B19V+ myocarditis in humans and transgenic B19V mice reflecting vascular damage. EMP profiles might permit differentiation between endothelial-cell-mediated diseases like myocardial B19V infection and other causes of myocarditis.