sVCAM-1 Concentrations Research Articles

Clinical characteristics and prognosis of serous body cavity effusions in patients with sepsis: a retrospective observational study

BackgroundCavity effusion is common in patients with infectious diseases. However, the incidence rate and characteristics of serous cavity effusions (SCE) in septic patients are not clear to date. The objective of this study was to investigate the incidence and characteristics of SCE in septic patients and to explore the correlations between the bloody effusions and the illness severity/prognosis in septic patients.MethodsFrom January 2010 to January 2015, a total of 214 patients with severe sepsis and septic shock were enrolled in this retrospective observational study. Thoracentesis or abdominal paracentesis was performed in 45 septic patients because of massive pleural effusions or ascites. The serum concentrations of VEGF, VEGFR, Ang, sICAM-1, sVCAM-1, E-selectin, Serpine1 and VE-cadherin in 45 septic patients underwent paracentesis were measured by enzyme-linked immunosorbent assay (ELISA).ResultsOf the 214 septic patients, 155 (72.4%) had SCE according to imaging or ultrasound manifestations. 45 subjects with SCE underwent therapeutic thoracentesis or abdominal paracentesis. Effusion laboratory analysis showed that exudates were predominant when compared with transudates (95.6% vs. 4.4%), and 16 (35.6%) patients suffered bloody effusions. Compared with patients with non-bloody effusions, those with bloody effusions showed higher critical illness scores (13 vs. 17 for APACHE II; 7 vs. 9 for SOFA), and higher mortality (6.9% vs. 62.5%). Moreover, patients with bloody effusions had delayed TT and APTT, increased D-dimer concentration, and higher serum levels of CRP and PCT (P < 0.05). In addition, the serum levels of Ang2, sVCAM-1 and E-selectin were significantly higher in patients with bloody effusions than in those with non-bloody effusions (P < 0.05). However, the serum level of VEGFR2 was lower in patients with bloody fluids (P = 0.025).ConclusionsThe incidence of serous cavity effusion is high in patients with sepsis. The septic patients with bloody effusions suffer a more inflammatory burden and a worse prognosis compared to septic patients with non-bloody effusions.

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.

Linking systemic angiogenic markers to synovial vascularization in rheumatoid arthritis.

BackgroundNeoangiogenesis is a crucial event to promote the development of the hyperplasic proliferative pathologic synovium in Rheumatoid arthritis (RA). Ultrasound (US) is sensitive for detection of power Doppler (PD) vascularization.ObjectiveTo explore the associations between a set of complementary circulating angiogenic markers and a comprehensive US assessment in patients with RA.Patients and methodsSerum levels of eight angiogenic markers were measured by quantitative ELISAs in a total of 125 patients with RA, who were all systematically assessed in parallel by PDUS, performed on 32 joints.ResultsSerum levels of soluble Vascular Cell Adhesion Molecule-1 (sVCAM-1) and Tie-2 were more likely to be increased in patients with synovial hyperemia detected on at least one joint (Power Doppler grade ≥1). sVCAM-1, Tie-2 and Angiostatin concentrations gradually increased together with the grade of the semiquantitative PDUS scale and concentrations of these three markers were markedly increased in patients with moderate to marked hyperemia (Power Doppler grade 2 and 3). Levels of sVCAM-1, Tie-2, and Angiostatin correlated with a global arthritis sum score, defined by the sum of the semiquantitative PDUS scores for all joints examined. Levels of Tie-2 and Placenta Growth Factor (PlGF) were associated with PDUS features indicating residual disease activity.ConclusionOur results support the relevance of measuring serum levels of vascular markers to evaluate the intensity and extent of synovial vascularization. Angiogenic markers, and particularly Tie-2, could be a valuable surrogate of active synovitis and their place in relation to PDUS in clinical practice deserve further investigation.

Periodontal therapy and endothelial function in coronary artery disease: A randomized controlled trial.

To assess the effects of periodontal treatment on endothelial function in patients with coronary artery disease. A randomized controlled trial was conducted with 69 patients with stable coronary disease and severe periodontitis. The test group received nonsurgical periodontal therapy consisting of personalized oral hygiene instructions, subgingival scaling, and root planing per quadrant, whereas the control group received equal treatment after the study period. Endothelial function was assessed by measurement of brachial artery flow-mediated dilation, concentrations of sVCAM-1, sICAM-1, and P-selectin in serum before and 3months after periodontal therapy. The test group exhibited statistically better periodontal parameters-plaque, probing depth, periodontal attachment loss, and bleeding on probing. No significant improvements were observed in the control (1.37%) and test (1.39%) groups in flow-mediated dilation, with no significant between-group difference. sVCAM-1 concentration increased in the control group (997.6±384.4-1201.8±412.5; p=0.03), whereas in the test group, no significant changes were observed (915.1±303.8-1050.3±492.3; p=0.17), resulting in a significant difference between the two groups (p=0.04). The same pattern was observed for concentrations of sICAM-1. Periodontal treatment did not provide better vasodilation in patients with coronary disease in a short-term follow-up period, although it maintained blood concentrations of markers of vascular inflammation.

Association between smoking status assessed with plasma-cotinine and inflammatory and endothelial biomarkers in HIV-positive and HIV-negative individuals.

Smoking is a major contributor to mortality and morbidity in HIV-positive individuals. Our primary objective was to evaluate the association between smoking status determined by plasma cotinine (P-cotinine) concentration and inflammatory and endothelial biomarkers in HIV-positive versus HIV-negative individuals. We studied eight inflammatory/endothelial biomarkers [high-sensitivity C-reactive protein (hsCRP), E-selectin, soluble vascular cell adhesion molecule 1 (sVCAM-1), soluble intercellular adhesion molecule 1 (sICAM-1), matrix metallopeptidase 9 (MMP-9), myeloperoxidase (MPO), tissue type plasminogen activator inhibitor 1 (tPAI) and endothelin] in 105 HIV-positive individuals and 105 HIV-negative individuals matched on age, sex and self-reported smoking status. Smoking status was determined using P-cotinine (a concentration > 14 ng/mL was defined as demonstrating exposure to smoke). We used linear regression models to (1) examine the association between smoking status and inflammatory/endothelial biomarkers in HIV-positive compared with HIV-negative individuals, and (2) to determine whether there was evidence to suggest that the impact of smoking status on the biomarkers differed between HIV-positive and HIV-negative individuals. Of the eight biomarkers, smokers had increased hsCRP, sICAM-1 and MMP-9 concentrations irrespective of HIV status and increasing P-cotinine concentration was associated with increasing hsCRP concentration. We found no interaction between smoking and HIV status. HIV infection was associated with increased hsCRP, E-selectin, sVCAM-1, sICAM-1 and MMP-9 concentrations. Self-reported smoking status differed substantially from smoking status assessed with P-cotinine. Several biomarkers were associated with smoking status and HIV status. However, our data do not indicate that the effects of smoking on the biomarkers differ between HIV-positive and HIV-negative individuals.

Adsorption of Soluble Immunoglobulin-Type Adhesion Molecules to Cellulose Acetate Beads.

Circulating levels of soluble intercellular adhesion molecule-1 (sICAM-1) and vascular adhesion molecule-1 (sVCAM-1) are elevated in patients with inflammatory bowel disease. Cellulose acetate (CA) beads are used as carriers for granulocyte and monocyte (GM) adsorptive apheresis (GMA). We investigated the effect of CA beads on sICAM-1 and sVCAM-1 plasma concentrations in vitro. Because GM adsorption to CA beads increased with a rise in the incubation temperature in our previous study, peripheral blood was incubated with and without CA beads at 5, 25, 37, or 43 °C and plasma sICAM-1 and sVCAM-1 was measured. The sICAM-1 and sVCAM-1 concentrations in samples incubated with CA beads were significantly lower than those without CA beads at all four temperatures. However, no significant differences were observed both sICAM-1 and sVCAM-1 plasma levels at the four different temperatures after incubation with CA beads. These results suggest that independent of incubation temperature, sICAM-1 and sVCAM-1 are likely to adsorb CA beads. These molecules may be a new index for predicting the therapeutic effects of GMA.

Biomarkers of endothelial dysfunction predict sepsis mortality in young infants: a matched\xa0case-control study

BackgroundReducing death due to neonatal sepsis is a global health priority, however there are limited tools to facilitate early recognition and treatment. We hypothesized that measuring circulating biomarkers of endothelial function and integrity (i.e. Angiopoietin-Tie2 axis) would identify young infants with sepsis and predict their clinical outcome.MethodsWe conducted a matched case-control (1:3) study of 98 young infants aged 0–59 days of life presenting to a referral hospital in Bangladesh with suspected sepsis. Plasma levels of Ang-1, Ang-2, sICAM-1, and sVCAM-1 concentrations were measured at admission. The primary outcome was mortality (n = 18); the secondary outcome was bacteremia (n = 10).ResultsAng-2 concentrations at presentation were higher among infants who subsequently died of sepsis compared to survivors (aOR 2.50, p = 0.024). Compared to surviving control infants, the Ang-2:Ang-1 ratio was higher among infants who died (aOR 2.29, p = 0.016) and in infants with bacteremia (aOR 5.72, p = 0.041), and there was an increased odds of death across Ang-2:Ang-1 ratio tertiles (aOR 4.82, p = 0.013).ConclusionsThis study provides new evidence linking the Angiopoietin-Tie2 pathway with mortality and bacteremia in young infants with suspected sepsis. If validated in additional studies, markers of the angiopoietin-Tie2 axis may have clinical utility in risk stratification of infants with suspected sepsis.

Evaluation of thrombosis-related biomarkers before and after therapy in patients with multiple myeloma.

BackgroundThrombosis is one of the complications in the clinical course of multiple myeloma (MM). Vascular endothelial cells and/or the hemostatic-coagulatory system are thought to play an important role in thrombosis of MM. In addition to melphalan-prednisone (Mel-P) therapy, several new therapeutic drugs such as lenalidomide or bortezomib have been developed and show effectiveness against MM. However, these new drugs also have risk of therapy-related thrombosis.MethodsWe assessed 103 MM patients and 30 healthy controls, using enzyme-linked immunosorbent assays to evaluate five biomarkers: platelet-derived microparticles (PDMP), plasminogen activator inhibitor-1 (PAI-1), high mobility group box protein-1 (HMGB1), endothelial protein C receptor (EPCR), and soluble vascular cell adhesion molecule-1 (sVCAM-1). The effects of Mel-P, bortezomib, and lenalidomide on the plasma concentrations of these biomarkers were investigated.ResultsThe plasma concentrations of PDMP, PAI-1, HMGB1, EPCR, and sVCAM-1 were higher in MM patients than in healthy controls. Mel-P, bortezomib, and lenalidomide therapies all reduced biomarker levels after treatment. However, when only patients with higher levels of EPCR were compared, differences were seen between the three therapies in the elevation of PDMP, HMGB1, and PAI-1.ConclusionThese results suggest that both MM and therapies for MM can induce a hypercoagulable state. The elevated risk of thrombosis conferred by hypercoagulability increases patient morbidity and mortality. Attention should be paid to therapy-related thrombosis when new therapeutic regimens are selected for MM patients.

Increased Soluble VCAM-1 and Normal P-Selectin in Cystic Fibrosis: a Cross-Sectional Study

PurposeAs life expectancy in cystic fibrosis (CF) increases, questions regarding its potential impact on cardiovascular health arise. Soluble vascular cell adhesion molecule 1 (sVCAM-1), P-selectin (sP-selectin) are proposed as biomarkers of cardiovascular disease. We aimed to: compare their concentrations in clinically stable CF patients and healthy subjects (HS) and verify whether they independently correlate with CF characteristics.MethodsSerum sVCAM-1 and sP-selectin levels were measured using ELISA. CF was characterized using: forced expiratory volume in 1 s, exocrine pancreatic and CF-related liver disease status, Pseudomonas aeruginosa colonization, serum high-sensitivity C-reactive protein, and body mass index (BMI). CFTR genotypes were classified as severe (classes I and II) or other.Results108 CF patients and 51 healthy subjects volunteered for the study. In the CF group BMI was lower (median [IQR]: 20.5 kg/m2 [18.4–22.2] vs. 21.6 kg/m2 [19.9–23.4], p = 0.02) and hsCRP levels were higher (3.6 mg/L [1.1–7.1] vs. 0.5 mg/dL [0.3–1.0], p < 10−10). While sVCAM-1 concentrations were greater in CF patients (1018 ng/mL [851–1279] vs. 861 ng/mL [806–979], p < 10−4), sP-selectin levels did not differ (155 ng/mL [129–188] vs. 156 ng/mL [144–177], p = 0.48). None of the multivariable regression models was valid for the prediction of sVCAM-1 and sP-selectin in CF.ConclusionsWe found higher sVCAM-1 concentrations in CF patients than in healthy subjects, which were not explained by CF characteristics. Further research is required to check whether sVCAM-1 is a marker of microangiopathy in CF.

Effects of Transport Temperature on the Stability of Inflammatory, Hemostasis, Endothelial Function, and Oxidative Stress Plasma Biomarker Concentrations.

A number of studies in critically ill patients are conducted outside the hospital. Specimens should ideally be transported from out-of-hospital setting to a laboratory using dry ice, but this approach is expensive and may not be feasible in some circumstances. We, therefore, examined the impact of temperature during transport of specimens on the precision of biomarker concentrations. To determine the effects of transport temperature conditions on biomarker concentrations in specimens processed within 1 h of collection. We simulated transport by storing specimens at four temperature conditions: packaged at -80°C (control), on dry ice (-79°C), on cold gel packs (4°C), and at room temperature (RT, 21°C). We examined eight biomarkers spanning four signaling domains- inflammation, hemostasis, endothelial dysfunction, and oxidative stress. We calculated mean, median, and percent difference for each biomarker concentration compared with the control transport temperature at -80°C in 26 subjects (16 hospitalized with severe sepsis and 10 non-hospitalized volunteers). Patients with severe sepsis had log-fold higher median concentrations of IL-6, hs-CRP, D-dimer, E-selectin, sICAM-1, and sVCAM-1 compared with non-hospitalized volunteers (P <0.05). When specimens were combined, we observed a ≤7% difference in the mean and median IL-6, hs-CRP, D-dimer, PAI-1, E-selectin, s-ICAM, s-VCAM, and nitrite concentrations for dry ice and cold gel packs transport compared with transport at -80°C (P>0.05). Larger differences (up to 12%) were observed when biomarker concentrations for PAI-1 and s-VCAM at room temperature were compared with transport at -80°C (P >0.05). Select inflammatory, coagulation, endothelial dysfunction, and oxidative stress biomarkers can be transported at 4°C on gel packs for 24 h with minimal effects on precision.

Soluble serum VCAM-1, whole blood mRNA expression and treatment response in natalizumab-treated multiple sclerosis

BackgroundNatalizumab reduces disease activity in multiple sclerosis (MS). Natalizumab binds to the very late antigen-4 and inhibits vascular cell adhesion molecule-1 (VCAM-1)-mediated transmigration of immune cells across the blood-brain-barrier. This is associated with decreased serum concentrations of soluble (s)VCAM-1 and an altered composition of immune cell-subsets in the blood. ObjectiveWe aimed to examine if sVCAM-1 serum concentrations and whole blood mRNA expression levels of immune activation biomarkers is associated with disease activity in natalizumab-treated MS-patients. MethodssVCAM-1 serum concentrations and whole blood mRNA expression were measured in blood samples from untreated RRMS-patients and from two independent groups of natalizumab-treated patients. ResultssVCAM-1 serum concentrations and whole blood expression of HLX1 and IL1B mRNA were lower, whereas expression of EBI3 mRNA was higher in natalizumab-treated MS-patients. Five genes were differentially expressed in clinically unstable natalizumab-treated MS-patients in the discovery but not in the validation group. ConclusionDecreased serum concentrations of sVCAM-1 and altered whole blood mRNA expression levels of a panel of immunomarkers, associated with natalizumab-treatment, are not sensitive markers of MS disease activity. However, decreased expression of pro-inflammatory HLX1 and IL1B and increased expression of immunoregulatory EBI3 may indicate a less pathogenic immune activation status in natalizumab-treated MS.

Soluble Forms of Intercellular and Vascular Cell Adhesion Molecules Independently Predict Progression to Type 2 Diabetes in Mexican American Families.

ObjectiveWhile the role of type 2 diabetes (T2D) in inducing endothelial dysfunction is fairly well-established the etiological role of endothelial dysfunction in the onset of T2D is still a matter of debate. In the light of conflicting evidence in this regard, we conducted a prospective study to determine the association of circulating levels of soluble intercellular adhesion molecule 1 (sICAM-1) and soluble vessel cell adhesion molecule 1 (sVCAM-1) with incident T2D.MethodsData from this study came from 1,269 Mexican Americans of whom 821 initially T2D-free individuals were longitudinally followed up in the San Antonio Family Heart Study. These individuals were followed for 9752.95 person-years for development of T2D. Prospective association of sICAM-1 and sVCAM-1 with incident T2D was studied using Kaplan-Meier survival plots and mixed effects Cox proportional hazards modeling to account for relatedness among study participants. Incremental value of adhesion molecule biomarkers was studied using integrated discrimination improvement (IDI) and net reclassification improvement (NRI) indexes.ResultsDecreasing median values for serum concentrations of sICAM-1 and sVCAM-1 were observed in the following groups in this order: individuals with T2D at baseline, individuals who developed T2D during follow-up, individuals with prediabetes at baseline and normal glucose tolerant (NGT) individuals who remained T2D-free during follow-up. Top quartiles for sICAM-1 and sVCAM-1 were strongly and significantly associated with homeostatic model of assessment—insulin resistance (HOMA-IR). Mixed effects Cox proportional hazards modeling revealed that after correcting for important clinical confounders, high sICAM-1 and sVCAM-1 concentrations were associated with 2.52 and 1.99 times faster progression to T2D as compared to low concentrations, respectively. Individuals with high concentrations for both sICAM-1 and sVCAM-1 progressed to T2D 3.42 times faster than those with low values for both sICAM-1 and sVCAM-1. The results were similar in women in reproductive age group and the remainder of the cohort. Inclusion of sICAM-1 and sVCAM-1 in predictive models significantly improved reclassification and discrimination. The majority of these results were seen even when the analyses were restricted to NGT individuals.ConclusionSerum concentrations of sICAM-1 and sVCAM-1 independently and additively predict future T2D and represent important candidate biomarkers of T2D.

Soluble Vascular Cell Adhesion Molecule-1 (sVCAM-1) Is Elevated in Bronchoalveolar Lavage Fluid of Patients with Acute Respiratory Distress Syndrome.

IntroductionPulmonary vascular endothelial activation has been implicated in acute respiratory distress syndrome (ARDS), yet little is known about the presence and role of endothelial activation markers in the alveolar space in ARDS. We hypothesized that endothelial activation biomarkers would be differentially expressed in bronchoalveolar lavage fluid from patients with ARDS compared with healthy volunteers, and that biomarker concentrations would be associated with ARDS severity.MethodsWe performed a cross-sectional analysis of data from 26 intubated patients with ARDS undergoing evaluation for clinically suspected ventilator-associated pneumonia and five healthy volunteers. Patients underwent bronchoalveolar lavage a median of five days after intubation. Healthy volunteers also underwent bronchoalveolar lavage. Endothelial activation biomarkers (soluble vascular cell adhesion molecule-1 [sVCAM-1], soluble endothelial selectin [sESEL], angiopoietin-1 [Ang-1] and angiopoietin-2 [Ang-2]) were measured in bronchoalveolar lavage fluid. Clinically suspected ventilator-associated pneumonia was confirmed with microbiologic culture data.ResultsPatients with ARDS had significantly higher median sVCAM-1 concentrations in the bronchoalveolar lavage fluid compared with healthy volunteers (985 vs 119 pg/mL, p = 0.03). Additionally, there was a trend toward greater bronchoalveolar lavage fluid sVCAM-1 concentrations among patients with moderate/severe compared to mild ARDS (1395 vs 209 pg/mL, p = 0.06). We did not detect significant differences in bronchoalveolar lavage fluid levels of sESEL, Ang-1 or Ang-2 between patients with ARDS and healthy volunteers. Median bronchoalveolar lavage fluid biomarker levels did not differ between patients with and without microbiologically-confirmed ventilator-associated pneumonia.ConclusionssVCAM-1 concentrations were significantly higher in the bronchoalveolar lavage fluid of patients with ARDS compared to healthy controls, and tended to be higher in moderate/severe ARDS compared to mild ARDS. Our findings add to the growing evidence supporting the concept that endothelial activation plays an important mechanistic role in the pathogenesis of ARDS. Further studies are necessary to characterize the role and/or clinical significance of sVCAM-1 and other endothelial activation markers present in the alveolar space in ARDS.

Interdependencies among Selected Pro-Inflammatory Markers of Endothelial Dysfunction, C-Peptide, Anti-Inflammatory Interleukin-10 and Glucose Metabolism Disturbance in Obese Women.

Background: Currently increasing importance is attributed to the inflammatory process as a crucial factor responsible for the progressive damage to vascular walls and progression of atherosclerosis in obese people. We have studied the relationship between clinical and biochemical parameters and C-peptide and anti-inflammatory IL-10, as well as selected markers of inflammation and endothelial dysfunction such as: CCL2, CRP, sICAM-1, sVCAM-1 and E-selectin in obese women with various degree of glucose metabolism disturbance.Material and methods: The studied group consisted of 61 obese women, and 20 normal weight, healthy volunteers. Obese patients were spited in subgroups based on the degree of glucose metabolism disorder. Serum samples were analyzed using ELISA kits. Results: Increased concentrations of sICAM-1, sVCAM-1, E-selectin, CCL2 and CRP were found in all obese groups compared to the normal weight subjects. In patients with Type 2 diabetes mellitus (T2DM) parameters characterizing the degree of obesity significantly positively correlated with levels of CRP and CCL2. Significant relationships were found between levels of glucose and sICAM-1and also E-selectin and HOMA-IR. C-peptide levels are positively associated with CCL2, E-selectin, triglycerides levels, and inversely with IL-10 levels in newly diagnosed T2DM group (p<0.05). Concentrations of IL-10 correlated negatively with E-selectin, CCL2, C-peptide levels, and HOMA-IR in T2DM group (p<0.05).Conclusion: Disturbed lipid and carbohydrate metabolism are manifested by enhanced inflammation and endothelial dysfunction in patients with simply obesity. These disturbances are associates with an increase of adhesion molecules. The results suggest the probable active participation of higher concentrations of C-peptide in the intensification of inflammatory and atherogenic processes in obese patients with type 2 diabetes. In patients with obesity and type 2 diabetes, altered serum concentrations of Il-10 seems to be dependent on the degree of insulin resistance and proinflammatory status.

Prophylactic Nrf2 Activation Halts Progression of the Severe Adult Phenotype of Sickle Cell Disease in Transgenic Mice

Transition from pediatric to adult care is associated with poor prognosis and a sharp rise in mortality in sickle cell disease (SCD). Hitherto, mechanisms that promote the severe adult phenotype of SCD have not been defined. We performed a longitudinal cohort study in thirty-two Townes transgenic mice (SS; n=16, AA; n=16) aged 1 month through to 10 months to identify prognostic factors of SCD severity. Thirty-eight percent of the SS mice died during this period while all the control AA mice survived (Log-rank Mantel Cox test, p<0.01). Hemoglobin (Hb) concentration declined sharply at 3 months in the SS mice while it remained unchanged in the age-matched AA mice. Worsening anemia was concomitant with increased concentrations of multiple markers of intravascular hemolysis including plasma heme (p=0.0019), plasma Hb (p=0.002), and lactate dehydrogenase, LDH (p=0.032) as the SS mice reached adulthood. Collectively, these data identified hemolytic stress as a component of the adult phenotype of SCD. An age-dependent increase in the concentration of vascular cell adhesion molecule-1 (VCAM-1) in the plasma of SS animals (p<0.05), but not in AA mice highlighted vascular inflammation as another component of the severe adult phenotype of SCD. We confirmed the link between age-related disease severity and vascular inflammation by demonstrating a 2-fold higher concentration of vascular endothelial cadherin (sVE-cad) in the plasma of SS mice at 3-months compared to the steady-sate values of the same marker when the mice were one month old (p<0.05). Since nuclear factor erythroid-2 factor 2 (Nrf2) controls the antioxidant response to hemolytic stress, we tested the hypothesis that this factor may influence the progression of SCD. We generated bone marrow chimeric sickle mice devoid of Nrf2 activity in the endothelium and in other non-hematopoietic tissues. The resulting chimeras had markedly more severe intravascular hemolysis and vascular inflammation defined by higher concentrations of sVCAM-1 (p<0.01) and sVE-cad (p<0.01) than age-matched SS mice with a full complement of Nrf2 activity. Next, we determined whether prophylactic activation of Nrf2 in 1 month SS mice would slow down the disease severity seen in adulthood. A group of newly weaned SS mice aged ~1 month were randomized to receive the Nrf2 activator 3H-1, 2-dithiole-3-thione (D3T; n=8), or a DMSO vehicle by oral gavage (0.5 mmole/kg, 3x/week). After eight weeks of treatment the Hb dropped by <2% in the D3T group compared to a 10% drop in the vehicle group. In addition, D3T treatment blunted the age-related worsening of intravascular hemolysis, which we initially observed in the longitudinal cohort, and confirmed in the vehicle treated animals, by the elevations in plasma heme (p<0.01), plasma Hb (p<0.01), plasma bilirubin (p<0.05) and LDH (p<0.05). Remarkably, D3T treatment reduced the mean plasma sVCAM-1 at 3 month (731.8±28.2) from a significantly higher value when the same animals were aged 1 month (882.4±36; p<0.01, n=8), as well as stabilizing the plasma concentration of sVE-cad with aging. On the contrary, both sVCAM-1 and sVE-cad levels rose significantly during the adult transition in the vehicle-treated SS mice (p<0.001). Overall, our data identify Nrf2 as an attractive therapeutic target to slowing down the progression of SCD during the pediatric to adult transition. DisclosuresArcher:Global Blood Therapeutics: Consultancy.

HDL-c is an independent predictor of IL-6 and sVCAM-1 concentrations

HDL-c is an independent predictor of IL-6 and sVCAM-1 concentrations

Elevated circulating vascular cell Adhesion Molecule-1 (sVCAM-1) is associated with concurrent depressive symptoms and cerebral white matter Hyperintensities in older adults.

BackgroundCirculating vascular adhesion molecule-1 (sVCAM-1) is a presumed marker of endothelial activation and dysfunction, but little is known about its association with mood. We hypothesized that elevated plasma concentrations of sVCAM-1 may be a marker of depressive symptoms due to cerebral vascular disease.MethodsWe studied 680 community-dwelling participants in the MOBILIZE Boston Study, aged 65 years and older. sICAM-1 and sVCAM-1 were measured by ELISA assay and depressive symptoms were assessed during home interviews using the Revised Center for Epidemiological Studies Depression Scale (CESD-R). Cerebral White Matter Hyperintensities (WMHs) were quantified by MRI in a subgroup of 25 participants.ResultsOne hundred seventy nine (27 %) subjects had a CESD-R Score ≥ 16, indicative of depressive symptoms. The mean sVCAM-1 concentration (±SD) was 1176 ± 417 ng/mL in a group with CESD-R Scores <16 and 1239 ± 451 ng/mL in those with CESD-R Scores ≥16 (p = 0.036). CESD-R Score was positively associated with sVCAM-1 (r = 0.11, p = 0.004). The highest quintile of sVCAM-1, which is indicative of endothelial dysfunction, was significantly associated with depressive symptoms compared to the lowest quintile (OR = 1.97 (1.14-3.57) p = 0.015). In a subset of subjects, sVCAM-1 concentration was positively correlated with cerebral WMHs volume (p = 0.018).ConclusionsThe association between high levels of sVCAM-1 and depressive symptoms may be due to endothelial dysfunction from cerebral microvascular damage. Future longitudinal studies are needed to determine whether sVCAM-1 can serve as a biomarker for cerebrovascular causes of depression.

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.

Impact of administration of folic acid on selected indicators of inflammation in patients with primary arterial hypertension.

The examination was carried out in 41 patients with primary arterial hypertension, aged 19-65 (21 men and 20 women), without complications of hypertension and/or coexisting diseases. The examined patients were administered 15 mg of folic acid once a day for 45 days. Before and after administration of folic acid, concentrations of folic acid, homocysteine, hsCRP, sICAM-1 and sVCAM-1 in serum were assessed. Concentrations of folic acid and homocysteine were determined using the immunoenzymatic method (Abbott) on an AxSYM analyzer. The level of C-reactive protein (CRP) was determined with an ultra-sensitive turbidimetric assay on a Dimension analyzer (Siemens). Next, concentrations of adhesion particles sICAM-1 and sVCAM-1 were assessed with the ELISA technique (R&D). After the administration of folic acid in patients with primary arterial hypertension, a significant decrease in median concentrations of homocysteine in blood was observed. Simultaneously, the median hsCRP, ICAM-1 and VCAM-1 concentrations in serum in patients with primary arterial hypertension were significantly reduced. Administration of folic acid to persons with primary arterial hypertension in a dose of 15 mg/ day for 45 days caused a decrease in the concentration of homocysteine in serum. That could indirectly result in the decrease in concentrations of the indicators of inflammation (hsCRP, ICAM-1 and VCAM-1), as it is apparent from previous studies that hyperhomocysteinemia stimulates the synthesis of CRP and the expression of adhesion molecules.

Endocan — the new endothelial activation marker independently associated with soluble endothelial adhesion molecules in uraemic patients with cardiovascular disease

ObjectivesEndocan is a new marker of endothelial cell activation that mediates adhesion of leukocytes into endothelium. Soluble intercellular (sICAM-1) and vascular cellular (sVCAM-1) adhesion molecules play an important role in the prevalence of cardiovascular disease (CVD) in chronic kidney disease (CKD) patients. The aim of this study is to investigate whether endocan could affect the concentrations of sICAM-1 and sVCAM-1 in CKD patients, particularly in those with CVD. Design and methodsWe evaluated plasma endocan, sICAM-1, sVCAM-1 and the markers of inflammation: high sensitivity C-reactive protein (hs CRP), interleukin-6, tumor necrosis factor-α (TNF-α) and their interrelationships in 53 CKD patients (both with and without CVD) and 29 healthy controls. ResultsEndocan, sICAM-1, sVCAM-1 and inflammatory markers were significantly higher in CKD patients than in controls, and patients with CVD had levels significantly higher (except interleukin-6 and TNF-α) than those without CVD. The presence of CVD, ferritin, TNF-α and SBP were the independent predictors of endocan levels in the whole CKD group. In this group, the weak relationship was between endocan and sICAM-1 and sVCAM-1, but age was the only independent predictor of these adhesion molecules. The strong association between endocan and sICAM-1 and sVCAM-1 was exclusively observed in subgroup with CVD, and the low % of lymphocytes followed by increased endocan was identified as the independent variables significantly associated with these soluble molecule levels. ConclusionsThis study shows that plasma endocan is significantly increased and independently associated with sICAM-1 and sVCAM-1 levels in CKD patients with cardiovascular complications.