Elevated sVCAM-1 Research Articles

Diabetic Endothelial Cell Glycogen Synthase Kinase 3β Activation Induces VCAM1 Ectodomain Shedding.

Soluble cell adhesion molecules (sCAMs) are secreted ectodomain fragments of surface adhesion molecules, ICAM1 and VCAM1. sCAMs have diverse immune functions beyond their primary function, impacting immune cell recruitment and activation. Elevated sVCAM1 levels have been found to be associated with poor cardiovascular disease (CVD) outcomes, supporting VCAM1's role as a potential diagnostic marker and therapeutic target. Inhibiting sVCAM1's release or its interaction with immune cells could offer cardioprotection in conditions such as diabetes. Membrane-bound surface adhesion molecules are widely expressed in a wide variety of cell types with higher expression in endothelial cells (ECs). Still, the source of sCAMs in the circulation is not clear. Hypothesizing that endothelial cells (ECs) could be a potential source of sCAMs, this study investigated whether dysfunctional EC signaling mechanisms during diabetes cause VCAM1 ectodomain shedding. Our results from samples from an inducible diabetic mouse model revealed increased sVCAM1 plasma levels in diabetes. Protein analysis indicated upregulated VCAM1 expression and metalloproteases ADAM10 and ADAM17 in diabetic ECs. ADAMs are known for proteolytic cleavage of adhesion molecules, contributing to inflammation. GSK3β, implicated in EC VCAM1 expression, was found to be activated in diabetic ECs. GSK3β activation in control ECs increased ADAM10/17 and VCAM1. A GSK3β inhibitor reduced active GSK3β and VCAM1 ectodomain shedding. These findings suggest diabetic ECs with elevated GSK3β activity led to VCAM1 upregulation and ADAM10/17-mediated sVCAM1 shedding. This mechanism underscores the potential therapeutic role of GSK3β inhibition in reducing the levels of circulating sVCAM1. The complex roles of sCAMs extend well beyond CVD. Thus, unraveling the intricate involvement of sCAMs in the initiation and progression of vascular disease, particularly in diabetes, holds significant therapeutic potential.

SVCAM-1 as a Marker of Endothelial Dysfunction associated with Severe Course of a Novel Coronavirus Infection (COVID-19)

Aim. To study the association of the level of endothelial dysfunction marker sVCAM-1 with the severe course of COVID-19.Material and methods. The study included 100 patients with COVID-19, who were divided into 3 groups depending on the degree of lung damage based on the results of computed tomography (CT): group CT 1 – 29 patients, group CT 2 – 61 patients and the group CT 3 – 10 patients. In addition to the standard examination performed for coronavirus infection, all patients underwent carotid Doppler ultrasound, analysis of arterial stiffness indices (CAVI, ABI) using the VaSera device, and evaluation of the plasma sVCAM-1 concentration by ELISA.Results. The plasma sVCAM-1 concentration was significantly higher in the groups of patients with moderately severe (CT 2) and severe (CT 3) lung lesions than in patients with mild lesions (CT 1). In the general group of patients significant correlations were found between the plasma sVCAM-1 concentration and the level of oxygen saturation (r=-0.39, p=0.032), hospital length of stay (r=0.24, p=0.026), values of C-reactive protein (r=0.25, p=0.042), ferritin (r=0.38, p=0.021), LDH (r=0.52, p=0.015) , as well as the percentage of pulmonary involvement according to CT data at admission (r=0.41, p=0.019) and on the day of discharge (r=0.35, p=0.022). According to multivariate regression analysis, sVCAM-1 does not depend upon gender, age, body mass index (BMI), the presence of type 2 diabetes mellitus (T2DM) and hypertension, and is a marker associated with cytokine storm progression, intermediate negative dynamics according to CT data, and need for respiratory support. The presence of type 2 diabetes, as well as elevated sVCAM-1 concentrations, is associated with an increased risk of high-dose glucocorticosteroid therapy. The threshold levels of this marker were calculated for each of the above events. We revealed a correlation between the sVCAM-1 concentration and the carotid intimal medial thickness in the general group of patients (r=0.25, p=0.036).Conclusion. An increase in the plasma sVCAM-1 concentration reflects the progression of endothelial dysfunction, one of the key factors in the pathogenesis of COVID-19. The latter necessitates the need for endothelium protective therapy for these patients. The evaluation of sVCAM-1 in blood plasma is a promising diagnostic technique aimed at predicting the risk of a severe course of COVID-19 and its long-term health hazards.

Soluble adhesion molecules and functional outcome after ischemic stroke: A Mendelian randomization study

ObjectivesWe employed Mendelian randomization to determine whether genetically predicted circulating levels of endothelial-derived adhesion molecules (soluble intercellular adhesion molecule-1 [sICAM-1]), soluble vascular-leukocyte adhesion molecule-1 [sVCAM-1], and soluble-endothelial-leukocyte adhesion molecule [sE-selectin]) were associated with functional outcome after ischemic stroke. MethodsIndependent genetic variants robustly associated with soluble adhesion molecules, located at or close to the coding gene (cis), were used as genetic instruments. The functional outcome was evaluated using the 3-month modified Rankin Scale (mRS) score after ischemic stroke. A poor functional outcome was defined as mRS ≥ 3 at 3 months. We extracted summary data for functional outcome after ischemic stroke from the Genetics of Ischaemic Stroke Functional Outcome network (n = 6,021). ResultsGenetically elevated sICAM-1 (OR 1.28, 95% CI 1.05-1.56) and sE-selectin (OR 2.69, 95% CI 1.23-5.86) levels were related with poor post-stroke outcome. However, we found no evidence that genetically elevated sVCAM-1 were associated with post-stroke outcome (OR 1.36, 95% CI 0.39-4.66). ConclusionsWe found that genetically elevated higher sICAM-1 and sE-selectin levels are associated with poor post-stroke outcome. Further studies are warranted to evaluate the potential of ICAM-1 and E-selectin to be drug targets for post-stroke recovery.

Elevated Serum Levels of Progranulin and Soluble Vascular Cell Adhesion Molecule-1 in Patients with COVID-19.

BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with the angiocentric inflammation and angiogenesis, yet the molecules involved in this process remain to be determined.MethodsWe did a cross-sectional study of a cohort of patients with COVID-19 in Zunyi, China between February 1 and March 30, 2020. Serum concentrations of PGRN were determined by enzyme-linked immunosorbent assay in patients with COVID-19 at hospital admission and at discharge. In parallel, the serum levels of soluble adhesion molecules, vascular cell adhesion molecule-1 (sVCAM-1), intercellular adhesion molecule-1 (sICAM-1), P-selectin (sP-selectin), and E-selectin (sE-selectin) were assayed by a human adhesion molecule multiplex kit. The association between serum PGRN levels and other laboratory test results was analyzed by Spearman correlation analysis.ResultsAt baseline, the median serum PGRN levels in patients with COVID-19 were 94.8 ng/mL [interquartile range (IQR): 66.6–119.6 ng/mL], which was significantly elevated compared with those in healthy controls (46.3 ng/mL, IQR: 41.8–55.6 ng/mL). Moreover, the median serum sVCAM-1 levels were significantly higher in COVID-19 patients (1396.0 ng/mL, IQR: 1019.1–1774.8 ng/mL) than those in healthy controls (612.4 ng/mL, IQR: 466.4–689.3 ng/mL). However, the levels of sICAM-1, sP-selectin, and sE-selectin were not significantly elevated in patients with COVID-19 when compared to healthy controls. Further analysis showed that serum PGRN levels were significantly positively associated with sVCAM-1 (r= 0.675, P= 0.008) and inversely with sICAM-1 (r= −0.609, P= 0.021) and aspartate aminotransferase levels (r= −0.560, P= 0.037) in patients with COVID-19 at hospital admission. In COVID-19 patients, serum PGRN and sVCAM-1 levels fell significantly after successful treatment.ConclusionThe present study demonstrates elevated serum PGRN and sVCAM-1 levels in patients with COVID-19, which may provide clues as to the mechanisms underlying the pathogenesis of COVID-19. Further studies are warranted to evaluate the potential of PGRN and sVCAM-1 as biomarkers and investigate their role in the pathogenesis of COVID-19.

Proinflammatory mediators and their associations with medication and comorbid traits in children and adults with ADHD

Peripheral immune activation can influence neurodevelopment and is increased in autism, but is less explored in attention deficit hyperactivity disorder (ADHD). Patients with ADHD often display comorbid autism traits and gastrointestinal (GI) symptoms. Plasma protein levels of two acute phase reactants, C-reactive protein (CRP) and serum amyloid A (SAA), and two endothelial adhesion molecules, soluble intercellular adhesion molecule 1 (sICAM-1) and soluble vascular cell adhesion molecule 1 (sVCAM-1), which share important roles in inflammation, were analyzed in 154 patients with ADHD and 61 healthy controls. Their associations with ADHD diagnosis, severity, medication and comorbid autistic symptoms, emotion dysregulation and GI symptoms were explored. The ADHD patients had increased levels of sICAM-1 and sVCAM-1 compared to healthy controls (p = 8.6e–05, p = 6.9e–07, respectively). In children with ADHD, the sICAM-1 and sVCAM-1 levels were higher among those with ADHD medication than among children (p = 0.0037, p = 0.0053, respectively) and adults (p = 3.5e–09, p = 1.9e–09, respectively) without ADHD medication. Among the adult ADHD patients, higher sICAM-1 levels were associated with increased comorbid autistic symptoms in the domains attention to detail and imagination (p = 0.0081, p = 0.00028, respectively), and higher CRP levels were associated with more GI symptoms (p = 0.014). sICAM-1 and sVCAM-1 levels were highly correlated with each other, and so were CRP and SAA levels. To conclude, vascular inflammatory activity may be overrepresented in ADHD, with elevated sICAM-1 and sVCAM-1 levels and this may in children be a consequence of current ADHD medication, and in adults relate to increased comorbid autistic symptoms. Replication is warranted.

Antiretroviral therapy reduces but does not normalize immune and vascular inflammatory markers in adults with chronic HIV infection in Kenya.

Markers of monocyte/macrophage activation and vascular inflammation are associated with HIV-related cardiovascular diseases (CVD) and mortality. We compared these markers among African people living with HIV (PLWH) and HIV-negative adults, and examined risk factors associated with elevated biomarkers (>75th percentile) in PLWH on antiretroviral therapy (ART). Cross-sectional study. We measured serum concentrations of a gut integrity biomarker (intestinal-fatty acid binding protein), monocyte/macrophage activation biomarkers (soluble CD14 and CD163), and vascular inflammation biomarkers [soluble intercellular adhesion molecule 1 (sICAM-1) and soluble vascular adhesion molecule 1 (sVCAM-1)]. We assessed the relationship of these inflammatory parameters with HIV, using logistic regression adjusting for traditional CVD risk factors. Among the 541 participants, median age was 43 years and half were female. Among 275 PLWH, median CD4 T-cell count and duration of ART use was 509 cells/μl and 8 years, respectively. PLWH had significantly higher prevalence of elevated inflammatory biomarkers compared with HIV-negative individuals even after adjustment for traditional CVD risk factors. Compared with individuals without HIV, the prevalence of elevated biomarkers was highest among persons with detectable viral load and CD4 T-cell counts 200 cells/μl or less. In a subanalysis among PLWH, nadir CD4 T-cell count 200 cells/μl or less was associated with elevated soluble CD14 (sCD14); dyslipidemia with elevated sCD14, sICAM-1, and sVCAM-1; and overweight/obesity with reduced sCD14. Longer ART exposure (>4 years) was associated with reduced sVCAM-1 and sICAM-1. HIV and not traditional CVD risk factors is a primary contributor of monocyte/macrophage activation and inflammation despite ART. Anti-inflammatory therapies in addition to ART may be necessary to reduce these immune dysregulations and improve health outcomes of African PLWH.

Soluble vascular cell adhesion molecule-1 in patients with non-valvular atrial fibrillation

Background: Disturbances in atrial microcirculation is recognized as a risk factor for atrial fibrillation (AF). Aim: The aim of this study was to determine the associations between circulating soluble vascular cell adhesion molecule-1 (sVCAM-1) and the risk of AF and a one-year prognosis among consecutive inpatients. Methods: Eighty consecutive inpatients hospitalized due to non-valvular AF and 80 consecutive inpatients admitted for exacerbation of chronic coronary syndrome (control group) were enrolled in the study. A cardiologic workup was performed and blood sVCAM-1 concentration was determined using the ELISA method. Results: Patients with AF had similar blood sVCAM-1 concentration compared to the control group. AF patients treated with new oral anticoagulants (NOACs) were significantly less likely to have a sVCAM-1 concentration elevated above the median value than patients treated with warfarin (34.2% vs 65.8%; p = 0.01). Patients with an increased percentage of fat mass (FM) had lower sVCAM-1 concentration. The risk of all-cause mortality and MACE during follow-up rose in individuals with elevated sVCAM-1 (≥ 1242 and ≥ 587 ng/ml, respectively) with (OR; 95%CI): 5.39; 1.57-18.45; p = 0.007, and 6.00; 1.18-30.37; p = 0.03, respectively. Risk of death rose with increase in the ratio of sVCAM-1 and FM (1.02; 1.00-1.04; p = 0.019). Conclusions: Elevated sVCAM-1 was associated with all-cause mortality and MACE during one-year follow- up, but do not links the risk of AF. Use of NOACs may favorable affect endothelial function, A lower level of sVCAM-1 in obese patients may mediate the phenomenon of the “obesity paradox” in patients with AF.

Effects of a synbiotic on symptoms, and daily functioning in attention deficit hyperactivity disorder – A double-blind randomized controlled trial

Some prebiotics and probiotics have been proposed to improve psychiatric symptoms in children with autism. However, few studies were placebo-controlled, and there is no study on persons with an attention deficit hyperactivity disorder (ADHD) diagnosis. Our aim was to study effects of Synbiotic 2000 on psychiatric symptoms and functioning in children and adults with ADHD without an autism diagnosis. Children and adults (n = 182) with an ADHD diagnosis completed the nine weeks randomized double-blind parallel placebo-controlled trial examining effects of Synbiotic 2000 on the primary endpoints ADHD symptoms, autism symptoms and daily functioning, and the secondary endpoint emotion regulation, measured using the questionnaires SNAP-IV, ASRS, WFIRS, SCQ, AQ and DERS-16. Levels at baseline of plasma C-reactive protein and soluble vascular cell adhesion molecule-1 (sVCAM-1), central to leukocyte-endothelial cell adhesion facilitating inflammatory responses in tissues, were measured using Meso Scale Discovery. Synbiotic 2000 and placebo improved ADHD symptoms equally well, and neither active treatment nor placebo had any statistically significant effect on functioning or sub-diagnostic autism symptoms. However, Synbiotic 2000, specifically, reduced sub-diagnostic autism symptoms in the domain restricted, repetitive and stereotyped behaviors in children, and improved emotion regulation in the domain of goal-directed behavior in adults. In children with elevated sVCAM-1 levels at baseline as well as in children without ADHD medication, Synbiotic 2000 reduced both the total score of autism symptoms, and the restricted, repetitive and stereotyped behaviors. In adults with elevated sVCAM-1 at baseline, Synbiotic 2000 significantly improved emotion regulation, both the total score and four of the five subdomains. To conclude, while no definite Synbiotic 2000-specific effect was detected, the analysis of those with elevated plasma sVCAM-1 levels proposed a reduction of autism symptoms in children and an improvement of emotion regulation in adults with ADHD.Trial registration number: ISRCTN57795429.

Association of Endothelial Biomarkers with Cerebral MRI Perfusion Analysis in Patients with Sickle Cell Disease

Introduction Sickle cell disease (SCD) is associated with silent cerebral infarcts (SCI) which are related to neurocognitive damage. One of the major causes of SCI is the impaired cerebral oxygenation, which makes cerebral blood flow (CBF) an essential parameter to measure. Previous hemodynamic studies have shown elevated CBF and reduced cerebrovascular reserve (CVR) in patients with SCD (Helton 2015; Václavů 2018). CVR is known as the increase of CBF in response to vasoactive stimulus, relative to the baseline. The reduced CVR renders SCD patients susceptible to cerebral ischemia, especially under hypotensive or hypoxic conditions. Possible factors contributing to microvascular damage and thus reduced CVR include hemoglobin S polymerization, neutrophil activation and endothelial activation and adhesion. Previous studies examined the role of these factors in patients with SCD (Sins 2017; Al Najjar 2017). However, the association between the endothelial biomarkers and hemodynamic parameters is unknown in adult patients with SCD. In this study, we investigated the correlation between CBF and CVR and the adhesion molecules including sVCAM-1, sP-selectin, VWF-Ag and ADAMTS13. Additionally, we studied the association of these endothelial biomarkers with standard laboratory parameters. Methods This study was performed in accordance with the Declaration of Helsinki and was approved by the Review Board of Amsterdam UMC. For this study, 33 steady state patients with SCD (mean age 32.1 ± 10.7, 64% male, 29 HbSS, 4 HbSß) and 10 healthy volunteers (mean age 36,4 ± 15.9, 60% male, 2 HbAS, 8 HbAA) were included. Hematologic laboratory parameters were assessed using standard laboratory procedures. Plasma levels of sVCAM-1 and sP-selectin were determined using ELISA (R&D Systems, USA) and ADAMTS13 and VWF-Ag were measured with the INNOVANCE assay (Siemens Healthcare Diagnostics). For the CBF measurements, pseudo-continuous arterial spin labelling (pCASL) was acquired at 3T MRI (Philips Healthcare, The Netherlands). CBF was measured before and after acetazolamide (vasoactive stimulus) administration and subsequently CVR was calculated using the following equation: CVR = (CBFafter - CBFbefore) / CBFbefore x 100% Plasma levels of endothelial biomarkers were compared between groups using ANOVA test. Correlation between the parameters were measured using single regression model where p<0.05 was considered as statistically significant. Results sVCAM-1 levels and VWF-Ag were significantly higher in SCD patients compared to healthy controls (p < 0.01 and p = 0.01). ADAMTS13 and sP-selectin were not significantly different between the two groups (p = 0.06 and p = 0.33). sVCAM-1 was significantly associated with CBF, and parameters of hemolysis LDH and bilirubin in SCD patients (Fig. 1A and 2C). Negative correlation was observed between sVCAM-1 and hemoglobin (Fig. 1B). The relationship between sVCAM-1 and hemodynamic and laboratory parameters are shown in Table 1. No significant correlation was found between sVCAM-1, hemodynamic and standard laboratory parameters in healthy controls. VWF-Ag, ADAMTS13 and sP-selectin were not significantly associated with hemodynamic MRI parameters. Discussion Our results show elevated sVCAM-1 levels in sickle cell patients, strongly related to CBF. sVCAM-1 is an adhesion molecule and elevated plasma levels are found in patients with endothelial activation due to inflammation or atherosclerosis (Cook-Mills 2013; Cybulsky 2001). Previous studies showed elevated levels in sickle cell disease but no correlation with parameters of cerebral perfusion have been demonstrated yet (Antwi-Boasiako 2018; Kato 2005). The strong correlation with CBF is mostly related to the chronic hemolysis given the association found with hemoglobin levels and markers of hemolysis like LDH and bilirubin. In contrast to sVCAM-1, no such relation was found with other markers of endothelial activation such as VWF activity and sP-selectin levels. No correlation between endothelial markers and the CVR was demonstrated, suggesting that endothelial damage itself may not related to the impaired cerebral vasodilatation in response to a vasoactive stimulus. Conclusion Endothelial adhesion molecule sVCAM-1 showed a strong correlation with CBF and parameters of hemolysis, suggesting a relation between the hemolytic damage of endothelial cells and impaired cerebral perfusion. Disclosures Nur: Novartis Pharmaceuticals: Consultancy.

Effect of severe hyperemesis gravidarum on maternal vascular endothelial health: evaluation of soluble adhesion molecules

Purpose: This study aimed to clarify the effect of severe hyperemesis gravidarum (sHG) on maternal vascular endothelial health with evaluation of soluble adhesion molecules.Method: The study population consisted of two groups of pregnant participants between 18 and 35 years of age who were between 5 and 13 weeks of gestation: sHG group and a healthy control group. A group of 26 participants whose pregnancies were complicated by sHG was compared with 26 healthy participants regarding serum levels of the soluble adhesion molecules such as E-selectin, soluble intracellular cell adhesion molecule 1 (sICAM-1), and soluble vascular cell adhesion molecule one (sVCAM-1), as well as other biochemical markers. The two groups had similar baseline characteristics.Results: Maternal baseline characteristics were similar in both groups. Serum levels of E-selectin (p < .001), sICAM-1 (p < .001), and sVCAM-1 (p < .001) were higher in the sHG group compared with the control group. Higher blood urea nitrogen, creatinine, and sodium levels, serum osmolarity, and urine density (p < .001, < .001, .006, .041, and .001, respectively) were also observed in the sHG group compared with the control group.Conclusions: The findings of this study indicated that sHG could impact endothelial cell function and these changes represented hypovolemia and dehydration caused by severe vomiting. Large-scale studies are required to understand the clinical importance of this finding regarding the long-term consequences and underlying mechanisms of elevated sICAM-1, sVCAM-1, and sE-selectin synthesis.

Soluble vascular cell adhesion molecule-1 and magnesium sulfate with nifedipine treatment in Indonesian women with severe pre-eclampsia.

Endothelial cell activation in pre-eclampsia is associated with elevated soluble vascular cell adhesion molecule-1 (sVCAM-1) levels. The objective of the study was to determine whether sVCAM-1 levels in Indonesian women with pre-eclampsia were similar to other ethnic studies and to determine the effects of magnesium sulfate with nifedipine on blood pressure. A total of 61 pregnant women were admitted, who had normal pregnancy (n = 25) and severe pre-eclampsia (n = 36). Blood sampling was performed at admission to the study, 1h after placental separation, and 24h postpartum. sVCAM-1 and blood pressure levels were determined. The mean ages in normal pregnancy (n = 25) and in severe pre-eclampsia (n = 36) are 30.0 ± 3.4 years and 27.1 ± 6.1 years, respectively. Significantly elevated sVCAM-1 was seen in pre-eclampsia. No significant variation in sVCAM-1 levels during the study periods was seen in both groups of cohorts. Magnesium sulfate infusion and nifedipine significantly lowered the blood pressure level. Elevated sVCAM-1 levels were also seen in Indonesian women with severe pre-eclampsia. The placenta may not be the only source of elevated sVCAM-1 and that endothelial dysfunction persists beyond the postpartum period. Magnesium sulfate together with nifedipine significantly lowered blood pressure. The determination of elevated sVCAM-1 in pregnancy as a risk marker for endothelial dysfunction is therefore suggested.

Elevated Soluble Vascular Cell Adhesion Molecule-1 Is Associated With Cerebrovascular Resistance and Cognitive Function.

Elevated plasma soluble vascular cell adhesion molecule-1 (sVCAM-1) is a presumed marker of endothelial dysfunction, both in the brain and systemic circulation. Impairments in memory and cognition have been associated with cardiovascular diseases, but little is known about their relationships to abnormal cerebral endothelial function. We studied the cross-sectional association between sVCAM-1 and markers of cerebrovascular hemodynamics and cognitive function in 680 community-dwelling participants in the MOBILIZE Boston Study, aged 65 years and older. Cognitive function was assessed using the Hopkins Verbal Learning Memory Test and Trail Making Tests (TMTs) A and B. Global cognitive impairment was defined as Mini-Mental State Examination (MMSE) score less than 24. sVCAM-1 was measured by ELISA assay. Beat-to-beat blood flow velocity (BFV) and cerebrovascular resistance (CVR = mean arterial pressure / BFV) in the middle cerebral artery were assessed at rest by transcranial Doppler ultrasound. sVCAM-1 concentrations were higher among participants with an MMSE score <24 versus ≥24 (1,201±417 vs 1,122±494ng/mL). In regression models adjusted for sociodemographic characteristics and health conditions, increasing levels of sVCAM-1 were linearly associated with higher resting CVR (p = .006) and lower performance on the Hopkins Verbal Learning Memory (immediate recall and delayed recall) and adjusted TMT B tests (p < .05). Higher levels of sVCAM-1 were also associated with global cognitive impairment on the MMSE (odds ratio = 3.9; 95% confidence interval: 1.4-10.9; p = .011). In this cohort of elderly participants, we observed a cross-sectional association between elevated sVCAM-1 levels and both cognitive impairment and increased cerebrovascular resistance. Longitudinal studies are needed to determine whether elevated sVCAM-1 is a cause or consequence of cerebrovascular damage.

Circulating vascular cell adhesion molecule-1 is associated with cerebral blood flow dysregulation, mobility impairment, and falls in older adults.

Soluble vascular cell adhesion molecule-1 (sVCAM-1) is associated with hypertension, vascular inflammation, and systemic endothelial dysfunction. We evaluated whether elevated plasma sVCAM-1 is associated with impaired cerebrovascular function and mobility impairments in elderly people. We studied the cross-sectional relationships between plasma sVCAM-1 level, gait speed, and cerebrovascular hemodynamics, and its longitudinal relationship with falls in 680 community-dwelling participants aged ≥65 years in the Maintenance of Balance, Independent Living, Intellect, and Zest in the Elderly (MOBILIZE) Boston Study. Falls were recorded prospectively for 1 year on daily calendars. sVCAM-1 was measured by ELISA assay and beat-to-beat blood flow velocity in the middle cerebral artery during rest and in response to changes in end-tidal CO2 was measured by transcranial Doppler ultrasound. sVCAM-1 concentration was 1094±340 ng/mL in normotensives, 1195±438 ng/mL in controlled hypertensives, and 1250±445 ng/mL in uncontrolled hypertensives (P=0.008). The mean resting blood flow velocity and cerebral vasomotor range were, respectively, 41.0±10.3 cm/s and 1.3±0.4 cm/s per millimeter of mercury. Elevated sVCAM-1 levels indicative of endothelial dysfunction were associated with reduced resting blood flow velocity (P=0.017) and cerebral vasomotor range (P=0.0048). Elevated sVCAM-1 levels were associated with slower gait speed (<0.8 m/s; odds ratio, 3.01; 95% confidence interval, 1.56-5.83; P=0.0011) and an increased odds of injurious falls (odds ratio, 2.4; 95% confidence interval, 1.4-4.2; P=0.0028). An elevated sVCAM-1 level may be a marker of cerebral blood flow dysregulation because of endothelial damage from hypertension. It may also signal the presence of cerebral microvascular disease and its clinical consequences, including slow gait speed and falls.

Biochemical and C-Reactive Protein Alterations in Myocardial Infarction Periodontitis Patients

Periodontitis (PD) is a risk factor for acute myocardial infarction (AMI). C-reactive protein (CRP) is elevated in PD. The aim of this study was to investigate biochemical alterations among AMi with PD. Thirty non-AMI (25 non-PD and only 5 PD) and 30 AMI (13 PD and 17 non-PD) patients were participated. Serum CRP, tumor necrosis factor alpha (TNF-α), total cholesterol, low-density lipoprotein cholesterol, protein carbonyl (PC) contents, soluble vascular cell adhesion molecule-1 (sVCAM-1), adiponectin, creatine kinase, resistin, catalase and superoxide dismutase (SOD) levels were measured. AMI-PD elicited significant differences in percentage hypertension, diabetes, serum creatine kinase, cholesterol and low-density lipoprotein cholesterol. CRP among AMI-PD and non-AMI-PD was increased by 73.4% and 31.3%, respectively. The level of PC contents was increased significantly among AMI-PD and non-AMI-PD by 47.62% and 33.3%, respectively. Catalase and SOD levels were significantly decreased in AMI-PD by 33.7% and 34.1%, respectively; however, their levels among non-AMI-PD were significantly increased by 35.7% and 28%, respectively. TNF-α, sVCAM-1 and resistin levels among AMI-PD were increased by 134.3%, 68.8% and 25.5%, respectively; however, TNF-α and sVCAM-1 levels among non-AMI-PD were increased significantly by 21.4% and 29.4%, respectively. Adiponectin level produced insignificant changes. PD prevalence among AMI associated with elevated serum CRP, PC contents, sVCAM-1, TNF-α and resistin levels concurrent with declines in SOD and catalase enzymes. In conclusion, among nondiabetic, nonsmoking patients suffering from AMI, PD is highly prevalent and associated with elevated serum CRP, PC contents, sVCAM-1, TNF-α and resistin levels, associated with significant declines in antioxidant enzymes with insignificant change in serum adiponectin level.

Weight loss and vascular inflammatory markers in overweight women with and without polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is associated with increased cardiovascular disease risk. The effect of weight loss on the vascular inflammatory markers plasminogen activator inhibitor-1 (PAI-1), asymmetric dimethylarginine (ADMA), soluble vascular cell adhesion molecule-1 (sVCAM-1) and intracellular adhesion molecule-1 (sICAM-1) is unknown. Overweight women with (n=14) and without (n=13) PCOS of comparable age and body mass index undertook an 8-week weight-loss programme. Women with PCOS had elevated PAI-1, sVCAM-1 and sICAM-1 before and after weight loss compared with the controls. For all women, sVCAM-1 (P=0.026) and sICAM-1 (P=0.04) decreased with weight loss. Women with PCOS have elevated inflammatory markers, which are partially reduced by weight loss.

Elevated urinary sVCAM-1, IL6, sIL6R and TNFR1 concentrations indicate acute kidney transplant rejection in the first 2 weeks after transplantation

We tested the hypothesis that increased urinary cytokine concentrations may indicate an acute kidney transplant rejection. Eight patients with an early rejection in their protocol biopsy about 14days after transplantation (group A), 9 patients with a biopsy proven rejection 2–3months after transplantation (group B) and 18 patients without acute rejection in their protocol biopsies both at 14days and 3months (group C, represents the control group) were chosen for this study. At the time of biopsy, the mean urinary concentration of interleukin 6 (IL6), soluble IL6 receptor (sIL6R), tumor necrosis factor receptor 1 (TNFR1), and soluble vascular cell adhesion molecule −1 (sVCAM-1) were significantly higher in patients with an early acute transplant rejection, i.e. in group A compared to patients in the control group (p<0.01). Additionally we found already 14days after transplantation significantly higher concentrations of urinary sIL6R and sVCAM-1 in group B patients who suffered of late acute rejection compared to patients with no acute rejection (group C, p<0.05). No significant correlation could be shown for interleukin 1 receptor antagonist (IL1ra), TNF, and TNFR2. In conclusion, elevated urinary concentrations of IL6, sIL6R, TNFR1 and sVCAM-1 clearly indicate an early acute transplant rejection. Especially sVCAM-1 may also serve as an early marker of an upcoming late rejection. However, further studies are warranted to verify the value of individual cytokine profiles to predict acute rejection episodes.

Biomarkers of structural remodelling and endothelial dysfunction for prediction of cardiovascular events or death in patients with atrial fibrillation

Atrial fibrillation (AF) is associated not only with inflammation but also with structural remodelling and altered endothelial activation which may contribute to clot formation, embolization and mortality. We aimed to determine the predictive value of single-time biomarker analysis for prediction of outcome in patients with AF. We conducted a prospective study to evaluate if biomarkers of structural, electrical or endothelial remodelling are predictive of cardiovascular events (composite primary endpoint of myocardial infarction, stroke, peripheral embolism or death). Secondary endpoint was all-cause mortality. Patients with any type of AF and without active inflammatory conditions were eligible. Plasma samples were collected for ELISA analysis of biomarkers (inflammation [hsCRP, sCD40L], structural [MMP-2] and endothelial remodelling [vWF, sVCAM-1]) at enrolment. Patients (n = 278) were followed for 28 ± 12 (median 32) months. Eighty-eight individuals (32%) experienced a primary outcome event, including 8 (2.9%) with myocardial infarction, 13 (4.8%) with stroke and 4 (1.5%) with peripheral embolism. Predictors of the primary endpoint were age >75 years, CHADS(2)-score >2, LVEF <35%, diabetes, presence of an ICD/pacemaker, elevated vWF, sVCAM-1 and MMP-2 levels. On multivariate regression analysis, only age >75 years, sVCAM-1 and MMP-2 levels remained independently associated with the endpoint. There were 75 deaths during follow-up. Age >75 years, reduced LVEF, elevated sVCAM-1 and MMP-2 levels were predictors of all-cause mortality. In this cohort of AF patients, old age, elevated sVCAM-1 and MMP-2 levels were associated with cardiovascular events. Our data indicate that single-time biomarker assessment may be a useful tool to improve risk stratification schemes.

Pro-atherogenic cytokine profile of patients with suspected obstructive sleep apnea

Systemic inflammation is important in the pathogenesis of cardiovascular disease (CVD). We sought to characterize the systemic inflammatory profile associated with obstructive sleep apnea (OSA). Adult patients referred for suspected OSA at the University of British Columbia Hospital Sleep Disorders Program were recruited for our study. Patients using HMG CoA inhibitors or a history of CVD were excluded. Fasting serum samples were obtained the morning after their diagnostic polysomnograms. Samples were tested for the following circulating inflammatory mediators: interferon gamma; interleukins 1B, 6, and 8; intercellular and vascular cell adhesion molecules (sICAM-1 and sVCAM-1); and leptin using a multiplex Luminex System. There were 176 patients; 68% were male, mean age = 50 +/- (SD) 11 years, mean apnea/hyponea index (AHI) = 22.9 +/- 22/h, mean desaturation (i.e. % of sleep time spent below an oxyhemoglobin saturation of 90%) = 5.4% +/- 15, and mean body mass index (BMI) = 32.2 +/- 8 kg/m(2). In univariate analyses, only leptin, sVCAM-1, and sICAM-1 were significantly associated with indices of OSA severity (i.e. AHI and/or desaturation). In multivariate linear regression analyses that controlled for BMI, gender, age, and current smoking; desaturation persisted as a significant independent predictor for elevated sVCAM-1 and leptin. We did not find significant associations between OSA and markers of activated innate immunity (IL-1B, 6, and 8). However, OSA severity was independently associated with serum levels of sVCAM-1 and leptin; these may represent mechanisms involved in the pathogenesis of OSA-related CVD.

Elevation of plasma concentration of adhesion molecules in late‐life depression

Late-life depression may be associated with vascular disease. The purpose of the study was to investigate this association by determining the levels of soluble adhesion molecules (sICAM-1 and sVCAM-1) which represent markers of ischemia-induced inflammation in elderly individuals with depression. Blood samples were obtained from 33 subjects with depression selected from a community-dwelling population after screening with the Geriatric Depression Scale, and 33 matched controls. Serum concentrations of sICAM-1 (ng/mL) and sVCAM-1 (ng/mL) were measured in both groups. Depressed patients (Group A) possessed significantly higher sICAM-1 levels compared to healthy controls (Group B) (674.94 +/- 166.90 ng/ml vs 467.05 +/- 231.26 ng/ml, respectively, p < 0.01). Similarly the same groups demonstrated elevated sVCAM-1 levels compared to controls (572.14 +/- 182.20 ng/ml vs 449.04 +/- 285.27 ng/ml, p < 0.05); a difference that in both cases remained significant after adjustment for potential confounders (gender, smoking, presence of metabolic syndrome). These findings indicate an association between high serum levels of VCAM-1, and ICAM-1 and depression in the elderly and further support the vascular depression hypothesis, which has important implications for the understanding and management of late-life depression.

Elevated Soluble Vascular Cell Adhesion Molecule–1, Elevated Homocyst(e)inemia, and Hypertriglyceridemia in Relation to Preeclampsia Risk

We examined the relationship of maternal plasma concentrations of soluble vascular cell adhesion molecule-1 (sVCAM-1), a specific marker of endothelial dysfunction, and risk of preeclampsia. We also evaluated the relationship in the presence and absence of maternal hypertriglyceridemia and hyperhomocystein(e)mia. A total of 170 women with preeclampsia and 184 control subjects were included in this case-control study analysis. Maternal postdiagnosis plasma sVCAM-1 concentrations were determined using immunoassays. Total plasma homocysteine (tHcy) was measured using high-performance liquid chromatography with electrochemical detection procedures; and triglyceride concentrations were determined using standard enzymatic procedures. Logistic regression procedures were used to estimate odds ratios (OR) and 95% confidence intervals (CI) adjusted for confounders. The relative risk of preeclampsia (as estimated by the OR) was increased 3.6-fold for women with sVCAM-1 concentrations >/=842 ng/mL compared with women who had lower concentrations (OR = 3.6; 95% CI 1.8 to 7.4). Of the three biological markers investigated, elevated sVCAM-1 concentrations was most strongly related to preeclampsia risk (OR = 4.6, 95% CI 1.6 to 13.5), followed by hyperhomocysten(e)mia (OR = 2.4, 95% CI 0.8 to 7.4) and hypertriglyceridemia (OR = 2.1, 95% CI 0.9 to 5.0). Compared with women who did not have any of the three risk factors, those with all three risk factors had an extremely high risk of preeclampsia (OR = 26.4; 95% CI 8.5 to 81.9). These findings suggest that elevated sVCAM-1 concentrations are associated with an increased risk of preeclampsia. Our findings extend the literature by documenting progressively increased risk with increasing numbers of biological markers of dyslipidemia and endothelial dysfunction.