sE-selectin Concentrations Research Articles

Relationship of adhesion molecules (ICAM-1 and E-selectin) with ABO blood groups in patients hospitalized with acute myocardial infarction.

Adhesion molecules, sICAM-1 and sE-selectin appear to have a major role in the pathogenesis of coronary artery disease (CAD). The focus of this study was to investigate the relationship of sICAM-1 and sE-selectin with ABO blood groups in Pakistani patients hospitalized with acute myocardial infarction (AMI). In a case-control study, 116 patients of acute myocardial infarction (AMI) and 116 healthy controls (age range for both: 30 years to 70 years; both males and females) were randomly selected from the Aga Khan University and National Institute of Cardiovascular Diseases, Karachi with informed consent. The blood samples were obtained and analyzed for ABO blood groups and serum levels of sICAM-1 and sE-selectin using kit methods. Statistical tests including independent sample t-test and Two-way ANOVA were used to study the association of these adhesion molecules with blood groups in AMI patients and healthy controls. Duration of the study was from July 2021 to June 30, 2023. Mean serum levels of sICAM-1 were significantly higher in AMI patients compared to healthy controls (342±159 mg/dl vs. 227±104 mg/dl; p-value<0.001). Similarly, serum levels of sE-selectin were also significantly higher in AMI patients compared to healthy controls (53.6±26.9 mg/dl vs. 40.7± mg/dl; p-value<0.001). Moreover, mean concentrations of sICAM-1 and sE-selectin for the interaction between subject type (cases and control) and blood groups were statistically significant (p-value = 0.007 and p-value = 0.035, respectively). There is an association of adhesion molecules, sICAM-1 and sE-selectin with ABO blood groups in Pakistani patients hospitalized with AMI.

The effects of statins on cardiovascular and inflammatory biomarkers in primary prevention: A systematic review and meta-analysis

Abstract Background Statins are well-established for their treatment of cardiovascular disease (CVD) due to their cholesterol-lowering effects and potential anti-inflammatory properties. Although previous systematic reviews demonstrate that statins reduce inflammatory biomarkers in the secondary prevention of CVD, none examine their effects on cardiac and inflammatory biomarkers in a primary prevention setting. Aims and Methods We conducted a systematic review and meta-analysis to examine the effects of statins on cardiovascular and inflammatory biomarkers among individuals without established CVD. The biomarkers included are: cardiac troponin, N-terminal pro B-type natriuretic peptide (NT-proBNP), C-reactive protein (CRP), tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), soluble vascular cell adhesion molecule (sVCAM), soluble intercellular adhesion molecule (sICAM), soluble E-selectin (sE-selectin) and endothelin-1 (ET-1). A literature search was performed through Ovid MEDLINE, Embase and CINAHL Plus for randomized controlled trials (RCTs) published up to June 2021. Results Overall, 35 RCTs with 26,521 participants were included in our meta-analysis. Data was pooled using random effects models presented as standardized mean differences (SMD) with 95% confidence intervals (CI). Combining 36 effect sizes from 29 RCTs, statin use resulted in a significant reduction in CRP levels (SMD -0.61; 95% CI -0.91, -0.32; P&amp;lt;0.001). This reduction was observed for both hydrophilic (SMD -0.39; 95% CI -0.62, -0.16; P&amp;lt;0.001) and lipophilic statins (SMD -0.65; 95% CI -1.01, -0.29; P&amp;lt;0.001). There were no significant changes in serum concentrations of cardiac troponin, NT-proBNP, TNF-α, IL-6, sVCAM, sICAM, sE-selectin and ET-1. Conclusions This meta-analysis demonstrates the effect of statins in reducing serum CRP concentrations in the context of CVD primary prevention, with no significant changes in the other cardiac and inflammatory biomarkers studied. The meta-analysis highlights the need for further high quality, large-scale trials evaluating the effects of statins on cardiac and inflammatory biomarkers in primary prevention.Figure 1.Effect of statins on CRP

The Effects of Statins on Cardiovascular and Inflammatory Biomarkers in Primary Prevention: A Systematic Review and Meta-Analysis.

Statins are well-established for their treatment of cardiovascular disease (CVD) due to their cholesterol-lowering effects and potential anti-inflammatory properties. Although previous systematic reviews demonstrate that statins reduce inflammatory biomarkers in the secondary prevention of CVD, none examine their effects on cardiac and inflammatory biomarkers in a primary prevention setting. We conducted a systematic review and meta-analysis to examine the effects of statins on cardiovascular and inflammatory biomarkers among individuals without established CVD. The biomarkers included are: cardiac troponin, N-terminal pro B-type natriuretic peptide (NT-proBNP), C-reactive protein (CRP), tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), soluble vascular cell adhesion molecule (sVCAM), soluble intercellular adhesion molecule (sICAM), soluble E-selectin (sE-selectin) and endothelin-1 (ET-1). A literature search was performed through Ovid MEDLINE, Embase and CINAHL Plus for randomised controlled trials (RCTs) published up to June2021. Overall, 35 RCTs with 26,521 participants were included in our meta-analysis. Data was pooled using random effects models presented as standardised mean differences (SMD) with 95% confidence intervals (CI). Combining 36 effect sizes from 29 RCTs, statin use resulted in a significant reduction in CRP levels (SMD -0.61; 95% CI -0.91, -0.32; P<0.001). This reduction was observed for both hydrophilic (SMD -0.39; 95% CI -0.62, -0.16; P<0.001) and lipophilic statins (SMD -0.65; 95% CI -1.01, -0.29; P<0.001). There were no significant changes in serum concentrations of cardiac troponin, NT-proBNP, TNF-α, IL-6, sVCAM, sICAM, sE-selectin and ET-1. This meta-analysis demonstrates that statin use reduces serum CRP levels in a primary prevention setting for CVD, with no clear effect on the other eight biomarkers studied.

Expression of ICAM-1 and E-selectin in different metabolic obesity phenotypes: discrepancy for endothelial dysfunction.

Endothelial dysfunction, the earliest vascular alteration, is a consequence of metabolic disorders associated with obesity. However, it is still unclear whether a proportion of obese individuals without metabolic alterations associated with obesity, defined as "metabolically healthy obesity (MHO)", exhibit better endothelial function. We therefore aimed to investigate the association of different metabolic obesity phenotypes with endothelial dysfunction. The obese participants without clinical cardiovascular disease from the MESA (Multi-Ethnic Study of Atherosclerosis) were allocated to the different metabolic obesity phenotypes based on their metabolic status, including MHO and metabolically unhealthy obesity (MUO). Associations of metabolic obesity phenotypes with the biomarkers of endothelial dysfunction, including soluble intercellular adhesion molecule-1 (sICAM-1) and soluble E-selectin (sE-selectin), were evaluated using multiple linear regression models. Plasma levels of sICAM-1 and sE-selectin were respectively measured in 2371 and 968 participants. Compared to the non-obese participants, those with MUO were associated with higher concentrations of sICAM-1 (β 22.04, 95% CI 14.33-29.75, P < 0.001) and sE-selectin (β 9.87, 95% CI 6.00-13.75, P < 0.001) after adjusting for confounders. However, no differences were found for the concentrations of sICAM-1 (β 0.70, 95% CI -8.91 to 10.32, P = 0.886) and sE-selectin (β 3.69, 95% CI -1.13 to 8.51, P = 0.133) in the participants with MHO compared to the non-obese participants. Individuals with MUO were associated with elevated biomarkers of endothelial dysfunction, but the association with endothelial dysfunction was not found in those with MHO, indicating that the individuals with MHO might exhibit better endothelial function.

Endothelial biomarkers and platelet reactivity on ticagrelor versus clopidogrel in patients after acute coronary syndrome with and without concomitant type 2 diabetes: a preliminary observational study

BackgroundPleiotropic effects have been implicated in clinical benefits of ticagrelor compared to thienopyridine P2Y12 antagonists. There are conflicting data regarding effects of ticagrelor vs. thienopyridine P2Y12 blockers on endothelial function. Our aim was to compare endothelial biomarkers and their relations with platelet reactivity in real-world patients after acute coronary syndrome (ACS) on maintenance dual antiplatelet therapy (DAPT) with ticagrelor or clopidogrel stratified by diabetes status.MethodsBiochemical indices of endothelial dysfunction/activation and platelet reactivity by multiple electrode aggregometry were compared in 126 stable post-ACS subjects (mean age: 65 ± 10 years, 92 men and 34 women), including patients with (n = 61) or without (n = 65) coexistent type 2 diabetes (T2DM) on uneventful maintenance DAPT with either ticagrelor (90 mg b.d.) or clopidogrel (75 mg o.d.) in addition to low-dose aspirin. Exclusion criteria included a complicated in-hospital course, symptomatic heart failure, left ventricular ejection fraction < 40% and relevant coexistent diseases except for well-controlled diabetes, mild renal insufficiency or hypertension.ResultsClinical characteristics were similar in patients on ticagrelor (n = 62) and clopidogrel (n = 64). The adenosine diphosphate-induced platelet aggregation and circulating soluble P-selectin (sP-selectin) were decreased in ticagrelor users irrespective of T2DM status (p < 0.001 and p < 0.01 for platelet reactivity and sP-selectin, respectively). Plasma levels of soluble vascular cell adhesion molecule-1 (sVCAM-1) were lower in T2DM subjects on ticagrelor vs. clopidogrel (758 ± 162 vs. 913 ± 217 µg/L, p < 0.01). In contrast, plasma sVCAM-1 was similar in non-diabetic patients on ticagrelor and clopidogrel (872 ± 203 vs. 821 ± 210 µg/L, p > 0.7). The concentrations of sE-selectin, monocyte chemoattractant protein-1 and asymmetric dimethylarginine did not differ according to the type of P2Y12 antagonist regardless of T2DM status. Platelet reactivity was unrelated to any endothelial biomarker in subjects with or without T2DM.ConclusionsOur preliminary findings may suggest an association of ticagrelor-based maintenance DAPT with favorable endothelial effects compared to clopidogrel users in stable post-ACS patients with T2DM. If proven, this could contribute to more pronounced clinical benefits of ticagrelor in diabetic subjects.

Serum sRAGE and sE-selectin levels are useful biomarkers of lung injury and prediction of mortality in calves with perinatal asphyxia

The objective of the present study was to evaluate the biomarkers specific to lung endothelial and epithelial damage in the determination of lung injury and its severity in calves with perinatal asphyxia and to evaluate their prognostic importance among survivors and non-survivor calves. Ten healthy calves and 20 calves with perinatal asphyxia were enrolled in the study. Clinical examination and laboratory analysis were performed at admission. Serum concentrations of soluble advanced glycation end-product receptor (sRAGE), soluble E-selectin (sE-selectin), clara cell secretory protein (CC16), and soluble intercellular adhesion molecule-1 (sICAM-1) were measured to assess lung injury. Venous pH, sO2, HCO3, and BE of calves with perinatal asphyxia were significantly lower than the healthy calves. sRAGE, sE-selectin, pCO2, and lactate were significantly high in calves with asphyxia. ROC analysis showed that sRAGE, sE-selectin, pCO2, lactate, and respiratory rate were higher while HCO3 and BE were lower in the nonsurvivor calves than survivors. In conclusion, serum sRAGE and sE-selectin concentrations highlight the utility of these biomarkers in determining lung injury in calves with asphyxia. Also, pH, pCO2, lactate, HCO3, BE, and respiratory rate along with serum sRAGE and sE-selectin were useful indicators in the prediction of mortality.

In Vivo Effects of Coffee Containing Javamide-I/-II on Body Weight, LDL, HDL, Total Cholesterol, Triglycerides, Leptin, Adiponectin, C-Reactive Protein, sE-Selectin, TNF-α, and MCP-1

BackgroundDiet plays an unequivocal role in the development of obesity. Interestingly, recent studies have demonstrated that coffee products containing javamide-I/-II may be commonly found in the market. However, there is no information about in vivo effects of coffee containing javamide-I/-II (CCJ12) on obesity-related metabolic factors (body weight, LDL, HDL, total cholesterols, triglycerides, adiponectin, and leptin) in nonobese people. ObjectivesThe objective of this study was to investigate in vivo effects of CCJ12 on these metabolic factors as well as inflammatory/cardiovascular disease risk factors [C-reactive protein (CRP), soluble E-selectin (sE-selectin), TNF-α, monocyte chemoattractant protein-1 (MCP-1)] in a nonobese model. MethodsSprague-Dawley male rats were fed a complete diet for 20 wk with either drinking water containing CCJ12 [coffee containing javamide-I/-II group (CG), n = 10] or unsupplemented drinking water [water control group (NCG), n = 10]. The amounts of javamide-I/-II in CCJ12 were quantified by HPLC. Water/food consumption and body weight were monitored weekly, and the concentrations of metabolic/inflammatory/cardiovascular disease risk factors were measured by ELISA. ResultsThere was no significant difference in water/food consumption between the NCG and CG during the study. Also, no significant difference was found in average body weights between the groups either. In addition, after 20 wk, both groups did not show any significant difference in plasma LDL, HDL, and total cholesterol concentrations. Likewise, adiponectin and leptin concentrations were not significantly different between the groups. As expected, the 2 groups did not show any significant difference in plasma concentrations of CRP and sE-selectin. Furthermore, there was no significant difference in plasma concentrations of TNF-α and MCP-1 between the groups. ConclusionsThe data suggest that CCJ12 may not have significant effects on the metabolic/inflammatory/cardiovascular disease risk factors in the CG, compared with the NCG.

Effect of the Renin-Angiotensin-Aldosterone System Reactivity on Endothelial Function and Modulative Role of Valsartan in Male Subjects with Essential Hypertension.

Background: The aim of the study was to evaluate the relationship between renin-angiotensin-aldosterone (RAA) system activity and reactivity, and the endothelial function profile in normotensive subjects (N), and in essential hypertensives (H), followed by analysis of the modulatory role of an angiotensin receptor blocker (ARB): valsartan, administered in the management of hypertension. Methods: A total of 101 male subjects were enrolled to the study: 31H and 70N. The nitric-oxide (NO) bioavailability (l-Arginine, asymmetric dimethylarginine (ADMA)), symmetric dimethylarginine (SDMA), endothelial vasodilative function (flow mediated dilation (FMD)), oxidative-stress markers (malonyldialdehyde (MDA), thiol index (GSH/GSSG), nitrotyrozine (N-Tyr)), and pro-inflammatory/angiogenic parameters (sICAM-1, sVCAM-1, PAI-1, sE-selectin, PAI-1, thromboxane -B2) were assessed at baseline, then after intravenous -l-arginine administration, which was repeated after the 4-day acetylsalicylic acid (ASA) administration (75 mg/24 h). In hypertensives, this whole protocol was repeated following 2 weeks of valsartan therapy. Results: No effect of valsartan and ASA on the flow-mediated vasodilation (FMD) and the NO bioavailability in hypertensives was observed. Administration of valsartan increased plasma renin activity (PRA), but without a decrease in the aldosterone levels. ASA treatment minimized the pre-existing differences between the groups, and increased the PRA in the N-subgroup with the highest ARR values. The blood concentrations of proinflammatory sICAM-1, sE-selectin, sVCAM-1, and PAI-1 were higher, whereas the anti-inflammatory 6-keto-PGF1 alpha level was lower in hypertensive subjects. The levels of angiogenic VEGF did not differ between groups. Conclusions: Our study does not confirm the modulative effect of valsartan on endothelial function. Normotensive men showed an increase in FMD after l-arginine administration, possibly indicating baseline impairment of the NO synthesis.

Identification of IL-18 and Soluble Cell Adhesion Molecules in the Gingival Crevicular Fluid as Novel Biomarkers of Psoriasis.

Psoriasis is a chronic immunoinflammatory skin disease. Although its diagnosis is clinical, differences in the appearance and severity of lesions pose a challenge for clinicians worldwide. The use of accessible biomarkers for psoriasis could aid in the early diagnosis and treatment of the disease. To date, evidence on the analysis of gingival crevicular fluid (GCF) molecules as novel, accessible, and reliable biomarkers for psoriasis is limited. This cross-sectional study compared the GCF levels of IL-18, soluble (s)ICAM-1, and sE-selectin in psoriatic patients (n = 42) and healthy controls (n = 39). Individuals with psoriasis not undergoing treatment and healthy individuals were included independent of periodontal status. GCF samples were collected, and a multiplex bead immunoassay was performed to quantify the levels of the target molecules. Psoriatic patients presented higher concentrations of IL-18 and lower concentrations of sE-selectin compared to controls (p < 0.05). No differences were found in the levels of sICAM-1 between the two groups (p > 0.05). Psoriasis was associated with IL-18 and E-selectin levels regardless of periodontal status, age, and smoking habit (p < 0.05). The areas under the receiver operating characteristic curve (ROC) for IL-18 and sE-selectin were 0.77 and 0.68, respectively. In conclusion, IL-18 and sE-selectin levels in the GCF could be promising biomarker for psoriasis.

Severe Persistent Pain and Inflammatory Biomarkers in Sickle Cell Disease: An Exploratory Study.

Severe pain is among the most common and deleterious symptoms experienced by individuals with sickle cell disease (SCD), of whom more than 50% report chronic pain. Despite this, the understanding of the biological contributors to persistent severe SCD pain is limited. This exploratory study sought to describe pain phenotypes based on frequency of severe pain experienced over 6 months and identify inflammatory biomarkers associated with pain phenotypes among individuals with SCD. This study used self-report and electronic health record data collected from 74 individuals enrolled in the Duke Sickle Cell Disease Implementation Consortium Registry. Plasma from previously collected blood specimens was used to generate inflammatory biomarker data using the Inflammation 20-plex ProcartaPlexTM panel. Descriptive statistics were used to describe the occurrence of severe pain over the past 6 months, and bi-variate analyses were used to evaluate the relationship between inflammatory biomarkers and pain phenotypes. Among the 74 participants included in this study, 33.8% reported severe pain occurring never or rarely, 40.5% reported severe pain occurring sometimes, and 25.7% reported severe pain occurring often or always. Soluble E-selectin (sE-selectin) was the only inflammatory biomarker significantly associated with the pain phenotype groups (p = 0.049). Post hoc comparisons identified that participants in the often/always severe pain group had significantly higher plasma concentrations of sE-selectin compared to those in the sometimes severe pain group (p = 0.040). Our findings provide preliminary evidence of the frequent occurrence of severe pain and that sE-selectin may be an objective biomarker for the frequent occurrence of severe pain in this population.

The Clinical-Stage sGC Stimulator IW-1701 Prevents Increase of Plasma Biomarkers of Intravascular Inflammation and Suppresses Leukocyte-Endothelial Interactions in Tnfα-Treated Mice

Soluble guanylate cyclase (sGC) is a heme containing signaling enzyme that catalyzes the formation of cyclic guanosine 3‘,5‘-monophosphate (cGMP) from GTP in response to nitric oxide (NO) binding to heme. The second messenger cGMP modulates many physiological processes including inflammation. Treatment with NO donors or inhibitors of cGMP-selective phosphodiesterase 9 (PDE9) significantly attenuates TNFα-induced intravascular inflammation in C57BL/6 and sickle cell mice. The anti-inflammatory effect of PDE9 inhibitors was augmented by co-administration of hydroxyurea (HU), which is the current standard of care for sickle cell disease. It has been proposed that HU may exert its anti-inflammatory effect by acting as an NO donor. sGC stimulators are small molecules that bind to sGC and enhance NO-dependent catalytic activity of the enzyme. Here we evaluated the effect of the sGC stimulator IW-1701 in the absence and presence of HU on biomarkers of intravascular inflammation, leukocyte-endothelial cell interactions and neutrophil trafficking in C57BL/6 mice.Treatment of C57BL/6 mice with TNFα (50 ng/mouse, i.p.) increased the plasma levels of biomarkers of endothelial cell activation (sP-selectin, sE-selectin, sICAM-1) and leukocyte activation (MIP-2, sL-selectin). Pretreatment of mice with IW-1701 (10 mg/kg, p.o.) reduced the increase in plasma concentrations of MIP-2 and sL-selectin following the TNFα challenge by 81% and 58%, respectively. The TNFα-induced increase in plasma levels of sP-selectin, sE-selectin and sICAM-1 were also inhibited by 31%, 37% and 34%, respectively in IW-1701-treated mice. Co-treatment with HU augmented the effect of IW-1701 on plasma concentrations of sE-selectin and sICAM-1 in TNFα treated mice.The effects of IW-1701, HU and the combination on leukocyte endothelial cell interactions was assessed using intravital microscopy of post-capillary venules of the mouse cremaster muscle. TNFα treatment of C57BL/6 mice decreased leukocyte velocity from 26.6±3.1 μm/sec to 5.5±0.7 μm/sec and leukocyte rolling flux from 43.3±7.1 cells/min to 16.1±2.7 cells/min as compared to control mice. Pre-treatment of mice with IW-1701 (10 mg/kg) alone increased leukocyte velocity and rolling flux to 10.3±1.1 μm/sec and 24.1±2.3 cells/min, respectively. Similarly, pre-treatment of mice with HU (100 mg/kg, p.o.) alone increased leukocyte velocity to 15.5±1.7 μm/sec and leukocyte rolling flux to 50.2±5.9 cells/min. Co-administration of IW-1701 in combination with HU further increased leukocyte velocity (19.7±1.9 μm/sec) and leukocyte rolling flux (64.5±5.5 cells/min) in post-capillary venules of the mouse cremaster muscle. Treatment with either IW-1701, HU, or the combination did not change the number of adherent leukocytes to the vascular wall following TNFα stimulation. To further evaluate the effect of IW-1701 on neutrophil extravasation and trafficking we used a peritoneal recruitment model. Intraperitoneal injection of TNFα induced accumulation of Gr.1 positive neutrophils in the mouse peritoneal cavity (4±0.4×105 PMNs/peritoneal lavage). Trafficking of PMNs into mouse peritoneum was attenuated by treatment of mice with HU (2.7±0.5×105 PMNs/peritoneal lavage). Co-administration of HU and IW-1701 further decreased the number of neutrophils extravasated into the peritoneum of TNFα-challenged mice (1.4±0.3×105 PMNs/peritoneal lavage).In summary, prophylactic treatment with IW-1701 inhibited the TNFα-induced increase in plasma levels of biomarkers of intravascular inflammation and attenuated the effect of TNFα on transient adhesive interactions between leukocytes and endothelial cells in mice. Co-administration of HU significantly reduced neutrophil trafficking and augmented the effect of IW-1701 on biomarkers of endothelial cell activation and transient adhesive interactions in the mouse cremaster muscle. This study supports further evaluation of the sGC stimulator IW-1701 to reduce complications associated with intravascular inflammation such as vaso-occlusive crisis in patients with sickle cell disease. DisclosuresTchernychev:Ironwood Pharmaceuticals: Employment, Other: own stock options. Feil:Ironwood Pharmaceuticals: Other: This research was sponsored by Ironwood Pharmaceuticals. Germano:Ironwood Pharmaceuticals: Employment, Other: own stock options of Ironwood Pharmaceuticals . Warren:Ironwood Pharmaceuticals: Employment, Other: own stock options of Ironwood Pharmaceuticals . Lonie:Ironwood Pharmaceuticals: Employment, Other: own stock options of Ironwood Pharmaceuticals . Feil:Ironwood Pharmaceuticals: Other: This research was sponsored by Ironwood Pharmaceuticals. Milne:Ironwood Pharmaceuticals: Employment, Equity Ownership. Hadcock:Ironwood Pharmaceuticals: Employment, Other: own stock options of Ironwood Pharmaceuticals . Chien:Ironwood Pharmaceuticals: Employment, Equity Ownership. Currie:Ironwood Pharmaceuticals: Employment, Equity Ownership. Graul:Ironwood Pharmaceuticals: Employment, Other: own stock options of Ironwood Pharmaceuticals .

The role of soluble E-selectin in HIV associated preeclampsia

ObjectiveTo determine the serum concentration of soluble E-selectin (sE-selectin) in HIV associated preeclampsia. Study DesignThe study population (n = 72) consisted of normotensive pregnant (n = 36) and preeclamptic (n = 36) women stratified by HIV status (negative vs. positive). Serum concentrations of sE-selectin were quantified using the MilliPlex multiplex immunoassay method. Statistical analyses were conducted using GraphPad Prism software. ResultsWhen stratified by pregnancy type and HIV status, serum sE-selectin levels were elevated in the preeclamptic HIV-negative group compared to the normotensive HIV-negative group (p = 0.0070**). Gestational age, systolic blood pressure, diastolic blood pressure and baby weight were statistically different across the study groups (p < 0.0001). ConclusionThis study demonstrates an elevation of sE-selectin in preeclamptic HIV-negative compared to the normotensive HIV-negative group. However, when stratified by HIV status, there was no significant difference observed in preeclamptic HIV-positive and normotensive HIV-positive groups. The findings of this small-scale study suggest that sE-selectin may be used as a biomarker or an early identifier of preeclampsia. Studies with large numbers should be considered to confirm our findings.

Maternal, Fetal, and Placental Selectins in Women With Pre-eclampsia; Association With the Renin-Angiotensin-System.

Selectins [endothelial (E), platelet (P), and leucocytes (L)] are a class of cell adhesion molecules, stimulated in response to inflammation. Pre-eclampsia is characterized by inflammation, and angiotensin II is pro-inflammatory. We hypothesized that circulating maternal and fetal concentrations and placental expression of selectins would be increased in women with pre-eclampsia and would be associated with the angiotensin receptors (AT1R and AT2R). Maternal and fetal blood and placental tissue was collected at delivery from White European normotensive controls (n = 17) and women with pre-eclampsia (n = 17). Soluble (s) E-, P- and L-selectin protein concentrations were measured by ELISA and placental protein expression was examined by immunohistochemistry. Maternal sE-selectin concentrations were increased in pre-eclampsia (P < 0.001); conversely fetal sE- and sP-selectin levels were lower in pre-eclampsia (P < 0.05 for both). Staining was mainly localized to the syncytiotrophoblast for all selectins. E-selectin expression was increased, while P-selectin was decreased in placental from pre-eclampsia (P < 0.05 for both); no differences were observed for L-selectin expression. Both E- and L-selectin were positively correlated (P < 0.008; P < 0.02) with AT2R placental expression, whilst P-selectin was negatively associated with AT1R (P < 0.005), all only in the pre-eclampsia group. This novel study reports maternal, fetal and placental expression of selectins in pre-eclampsia. The increased E-selectins reflect the endothelial dysfunction, characteristic of pre-eclampsia. In contrast, the reduced P-selectins and the positive association of placental AT2Rs with both E-and L-selectin in pre-eclampsia could be a protective mechanism to limit the endothelial dysfunction.

Endothelial Function in Children with Acute Lymphoblastic Leukemia (ALL) May Reflect the Clinical Outcome.

Endothelial dysfunction is a common feature of early complications of hemato-oncologic therapy. The aim of our study was to assess the profile of endothelial function at diagnosis time, then during initial treatment phase of acute lymphoblastic leukemia (ALL), and to verify the presence of its correlation with early clinical outcome (ECO). 28 ALL children and 18 healthy age-matched control ones were recruited. Study group was examined at baseline and at 33rd and 78th day of treatment. At each protocol step the endothelial function was assessed by measurement of sP-selectin (CD62-P), PAI-1(serpinE1), sE-selectin (CD62E), sICAM-1(sCD54), sVCAM-1(sCD106), and VEGF concentrations. Higher baseline sICAM-1 and sVCAM-1 levels and lower sP-selectin and VEGF were observed in children with ALL. sICAM-1, sVCAM-1, and sE-selectin levels were decreasing following the treatment with protocol I. Higher sE-selectin and lower baseline sICAM-1 levels were observed in children treated unsuccessfully. Lower PAI-1 levels were observed in children who survived. Higher baseline sE-selectin levels and lower sICAM-1 and VEGF were observed in children treated unsuccessfully. A decrease in sE-selectin and lower PAI-1 at the 78th day of therapy were associated with better ECO. High baseline VEGF and sE-selectin levels, significant increase in PAI-1, and low initial sICAM-1 levels are prognostics for poorer prognosis in the ALL children.

The correlation between serum E-selectin levels and soluble interleukin-2 receptors with relation to disease activity in localized scleroderma.

IntroductionScleroderma is a chronic connective tissue disease resulting in fibrosis.AimThe aim of the study was to determine the connection between sE-selectin and sIL-2R and the severity of skin lesions in various subtypes of LoS. Evaluation of disease severity, the location of skin lesions, the duration of symptoms and disease activity were assessed in relation to the three different LoS subtypes in patients with localized scleroderma.Material and methodsThe study included 42 patients with localized scleroderma and the control group consisted of 41 healthy subjects. All patients in the LoS study group had a confirmed diagnosis via skin biopsy and underwent serology testing for sE-selectin and sIL-2R concentrations by enzyme-linked immunosorbent assay (ELISA).ResultsSignificantly higher levels of sE-selectin and sIL-2R were observed in the LoS study group when compared with the control group (p < 0.001). The analysis showed a result close to statistical significance (p = 0.058) between sE-selectin concentration during the time of active disease in the LoS study group. The highest concentrations of sE-selectin and sIL-2R were observed in patients with the generalized subtype of LoS. A positive, statistically significant, curvilinear relationship was shown amid the modified Localized Skin Severity Index (mLoSSI) and sE-selectin and sIL-2R concentrations in the LoS study group.ConclusionsConcentrations of the circulating form of sE-selectin appear to be an adequate marker of the endothelial function, positively correlating with the severity of the disease. The proven correlation of sIL-2R concentrations with the severity of the disease indicates that it is a valuable prognostic factor for predicting the impending course of the disease.

P37. Alterations in maternal and fetal plasma soluble endothelial leukocyte adhesion molecule-1 (sE-selectin) concentrations in women with pre-eclampsia

Introduction Pre-eclampsia (PE) is an important cause of perinatal and maternal morbidity, especially when diagnosed at or before 34 weeks’ gestation (early-onset PE), and is characterised by endothelial dysfunction/inflammation. E-selectin belongs to the selectin family of adhesion molecules involved in guiding non-activated polymorphonuclear cells to areas of inflammation in the endothelial layer. sE-selectin is a sensitive and specific marker of endothelial dysfunction, thus may be important in PE. Objective To determine whether plasma sE-selectin concentrations differed between normotensive controls (NC) and PE, as well as sub-grouped in early- and late-onset (>34 weeks’ gestation) PE in matched maternal and fetal samples. Methods sE-selectin was measured by ELISA in maternal and fetal umbilical venous EDTA plasma from NC ( n = 17) or pre-eclamptic ( n = 17) pregnancy. Distribution-free statistical tests were used. Results In PE overall, maternal sE-selectin concentrations were raised compared to normotensive controls (median [IQR]: 7.6 [6.9, 8.5] vs. 5.0 [3.5, 8.2] ng/ml; P vs. 10.6 [7.9, 15.1] ng/ml; P P n = 5) and late-onset PE ( n = 12), only the early-onset had higher maternal sE-selectin ( P Conclusions The increased maternal plasma sE-selectin in pre-eclampsia reflects the endothelial dysfunction, possible due to oxidative stress, which is apparent only in the more severe early-onset PE. The lower levels in the fetal plasma and the lack of difference between maternal and fetal circulations from the pre-eclampsia suggest there may be a different regulatory mechanism in the fetus.

Effect of uncontrolled hyperglycemia on levels of adhesion molecules in patients with diabetes mellitus type 2.

Uncontrolled diabetes has become a major cause of mortality and morbidity by reason of vascular angiopathy. The aim of this study was to evaluate the concentrations of soluble forms of vascular adhesion molecule-1 (sVCAM-1), intercellular adhesion molecule-1 (sICAM-1), E-selectin, and thrombomodulin in patients with well-controlled and uncontrolled diabetes type 2. The study was conducted on 62 patients with diabetes. Group I consisted of 35 patients with well-controlled diabetes. The second group included 27 patients with uncontrolled diabetes with micro-albuminuria. A control group was made up of 25 healthy volunteers. The concentrations of sVCAM-1, sICAM-1, sE-selectin, and soluble thrombomodulin were assayed in plasma. Serum concentration of creatinine was measured and the plasma concentrations of fasting glucose and glycated hemoglobin (HbA1c) determined. Lower concentrations of ICAM-1 were found in the group of uncontrolled diabetes patients compared with those with well-controlled disease. In patients with uncontrolled diabetes, VCAM-1 levels were significantly higher compared with the group with well-controlled diabetes. In patients with uncontrolled diabetes a positive correlation was obtained between glomerular filtration rate and sE-selectin and a negative correlation between the levels of creatinine and ICAM-1, although there was a positive correlation between (HbA1c) and ICAM-1. The study confirmed the participation of the inflammatory process associated with impaired vascular endothelial function in the pathogenesis of type 2 diabetes. The opposite effect of uncontrolled hyperglycemia on adhesion molecules suggests different functions of VCAM-1 and ICAM-1 in complications of diabetes.

Skin autofluorescence as a novel marker of vascular damage in children and adolescents with chronic kidney disease.

BackgroundSkin autofluorescence (sAF) was examined as a marker of the accumulation of advanced glycation end products (AGEs) in tissues of children with chronic kidney disease (CKD) in relation to renal function, dialysis modality and markers of endothelial inflammation and dysfunction.MethodsA total of 76 children with CKD were enrolled in the study, of whom 20 children were on hemodialysis (HD), 20 were on peritoneal dialysis (PD) and 36 were treated conservatively. A control group of 26 healthy subjects was also included in the study. In all children, sAF intensity, carotid intima-media (cIMT) thickness and plasma concentrations of sE-selectin, matrix metalloproteinase 9 (MMP-9), tissue inhibitor of metalloproteinase 1 (TIMP-1), asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA) and plasminogen activator inhibitor type 1 (PAI-1) were measured.ResultsCompared to the controls, children with CKD had significantly elevated sAF levels. sAF in the children with CKD was positively correlated with sE-selectin, MMP-9, TIMP-1, ADMA, SDMA and PAI-1 levels. In the predialysis group (conservative treatment) sAF levels were positively correlated with sE-selectin and ADMA levels and negatively correlated with glomerular filtration rate. Multiple regression analysis showed a significant association of sAF with sE-selectin and MMP-9 in CKD children.ConclusionsThe results reveal that AGEs were accumulated in the children with CKD. This accumulation was related to early vascular changes and a number of biochemical vascular risk markers. sAF measurement, as a noninvasive method, may be useful for identification of clinical risk factors of vascular disease in CKD children.

Association of malnutrition-inflammation score, dialysis-malnutrition score and serum albumin with novel risk factors for cardiovascular diseases in hemodialysis patients

Background: This study was designed to investigate the associations between malnutrition-inflammation score (MIS), dialysis-malnutrition score (DMS) and serum albumin with novel risk factors for cardiovascular diseases (CVD) in hemodialysis (HD) patients. Methods: In this cross-sectional study, 291 HD patients were randomly selected from among 2302 adult HD patients in Tehran HD centers. The MIS and DMS were determined during one of the dialysis sessions in these patients. In addition, 4 mL blood was obtained before dialysis and analyzed for serum albumin and novel risk factors for CVD, including C-reactive protein (CRP), soluble intercellular adhesion molecule type 1 (sICAM-1), soluble vascular cell adhesion molecule type 1 (sVCAM-1), sE-selectin, malondialdehyde (MDA), nitric oxide (NO), endothelin-1 and lipoprotein (a) [Lp (a)]. Results: MIS and DMS were significantly positively correlated with serum CRP (p < 0.01) and sICAM-1 (p < 0.01), whereas serum albumin concentration was significantly negatively correlated with serum CRP (p < 0.01) and sICAM-1 (p < 0.01). There were no significant correlations between MIS, DMS and serum albumin with serum concentrations of sVCAM-1, sE-selectin, MDA, NO, endothelin-1 and Lp (a). Conclusion: This study indicates that protein-energy wasting indicators in HD patients are associated with serum CRP and sICAM-1, as two CVD risk factors.

Blood pressure disturbances and endothelial dysfunction markers in children and adolescents with type 1 diabetes

Objective: Being the earliest step on the way to atherosclerosis, endothelial dysfunction is particularly escalated in diabetes. This study aimed at assessing endothelial dysfunction and blood pressure disturbances in young patients with type 1 diabetes mellitus (T1DM) and defining their interrelations. Methods: The study group comprised 52 children and adolescents aged 14.07 ± 3.03 years, with T1DM duration 5.13 ± 2.18 years. 20 healthy controls with similar age and sex distribution were included. Chosen serum biochemical markers of endothelial damage: intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), sE-selectin, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) as well as ambulatory blood pressure monitoring (ABPM) were performed in all subjects. Results: Patients with T1DM displayed significantly higher concentrations of chosen markers of endothelial dysfunction compared to controls (sVCAM-1 (ng/ml): 951.56 ± 330.68 vs. 710.35 ± 162.12, TNF-α (pg/ml): 16.63 ± 8.32 vs. 9.41 ± 4.23, IL-6 (pg/ml): 3.38 ± 1.31 vs. 2.45 ± 0.81; p < 0.05). Within the study group subjects with an abnormal ABPM reading had significantly higher concentrations of sE-selectin compared with subjects with normal ABPM (in ng/ml: 45.71 ± 15.63 vs. 32.42 ± 11.95; p < 0.01). The study revealed a significant positive correlation between sE-selectin and systolic as well as diastolic pressure loads during the day period (respectively: r = 0.46, r = 0.60; p < 0.01). Conclusions: Endothelium dysfunction may be present early in the course of T1DM in children and adolescents. It seems to be related with blood pressure disturbances which highlights the need to intensify treatment in this group of patients.