Serum Levels Of Soluble E-selectin Research Articles

Association of soluble E-selectin and morning blood pressure surge in patients with essential hypertension

Background: Elevated soluble E-selectin which reflects a state of endothelial activation with subsequent vasoconstriction may elevate morning blood pressure (BP) surge. This study aimed to analyze soluble E-selectin serum concentrations in patients with essential hypertension against normotensive healthy individuals and to find a role of such molecule in the phenomenon of morning BP surge. Material and methods: In this case-control study, a 24-hour ambulatory blood pressure monitoring with recording of morning BP surge and serum soluble E-selectin levels were measured for a total of 90 patients (60 patients with essential hypertension and 30 normotensive subjects as a control). Results: Hypertensive patients had higher body mass index in comparison to control subjects (30.7 ± 2.3 kg/m 2 vs. 27 ± 3.2 kg/m 2 , p < 0.001). Serum uric acid levels were higher in hypertensive patients than control subjects (7.26 ± 2.60 mg/dL vs. 5.92 ± 1.15 mg/dL, p = 0.028). Hypertensive patients had higher left ventricular mass index (LVMI) (110.5 ± 19.2 g/m2 vs. 99.8 ± 9.5 g/m 2 , p = 0.001). Patients with essential hypertension have higher level of soluble E-selectin than normotensive participants (180.6 ± 96.1 vs . 75.9 ± 31.5 ng/mL, p < 0.001). Soluble E-selectin was positively correlated with morning BP surge (r = 0.696, p ≤ 0.001). Conclusion: Patients with essential hypertension have higher level of soluble E-selectin than normotensive. Soluble E-selectin was positively correlated with morning BP surge.

Assessment of Serum Levels of E-Selectin and L-Selectin in Alopecia Areata

Background: Alopecia Areata (AA) is an immune system disease that invades anagen Hair Follicles (HFs) and shows multifactorial etiology. One of the essential histopathological features of AA is a lymphocytic intrusion that envelops HFs. Soluble forms of Endothelial (E), Lymphocytic (L), and Platelets (P)-selectins are known markers of persistent bothering. There are limited examinations for the assessment of serum levels of soluble E-selectin, L-selectin, and P-selectin in patients with AA. Objectives: We assessed serum levels of soluble E-selectin and L-selectin in patients with in association with the control group to determine their role in the pathogenesis of the disease. Methods: The study included 30 patients with AA and 10 healthy subjects who served as controls. Blood samples were taken from all patients and controls. The serum levels of soluble E-selectin and L-selectin were determined with the Enzyme-linked Immunosorbent Assay (ELISA) method. Results: Higher levels of sE-selectin and sL-selectin were found in AA patients than in controls. There was a significant relationship between the higher serum levels of sE-selectin and the increased size of lesions with time. There was a significant positive correlation between the serum levels of sE-selectin and sL-selectin and the percentage of hair loss. Conclusions: This study showed that sE-selectin and sL-selectin may play a significant role in the pathogenesis of AA and might open a way to future treatments for this disease.

Pleiotropy of ABO gene: correlation of rs644234 with E-selectin and lipid levels.

The ABO gene has been widely studied and associated with many different diseases such as myocardial infarction and diabetes. Pleiotropic effects of the ABO locus have been demonstrated. Indeed it affects different phenotypes such as E- and P-selectins, triglycerides and total cholesterol. The goal of this work was to study the SNP rs644234 located in the ABO gene with different phenotypes related with diseases where the ABO gene has been involved. We analyzed the SNP rs644234 located in the ABO gene, by performing association studies with different lipid phenotypes as well as with the soluble E-selectin levels in 348 adults from the STANISLAS Family Study. The major rs644234*T allele was associated with increased levels of soluble E-selectin (p=8.7×10-12). According to the lipid phenotypes, the major rs644234*T allele was associated with decreased levels of apolipoproteins E (ApoE) (p=0.001) and low-density lipoprotein cholesterol (LDL-C) (p=0.032) but was associated with increased levels of high-density lipoprotein cholesterol (HDL-C) (p=0.013). The association of the HDL-C was especially significant in the male individuals (p=0.001). We confirmed that ABO is a major locus for serum soluble E-selectin levels variability, and we also correlated this gene with different lipid phenotypes. Furthermore, we demonstrated that this pleiotropic effect is independent. This is the first time that a correlation has been made between the ABO gene and the ApoE levels. According to these results, the major allele of this polymorphism may have a protective effect when it comes to cardiovascular related diseases, and more specifically when it comes to the lipid phenotypes.

Cardiovascular diseases-related GNB3 C825T polymorphism has a significant sex-specific effect on serum soluble E-selectin levels.

BackgroundThe C825T polymorphism (rs5443) of the Guanine Nucleotide-Binding protein subunit β3 (GNB3) gene has been associated with obesity, essential hypertension, atherosclerosis, coronary diseases, and cerebrovascular events, but with some sex-specific effects. Its association with inflammatory mediators such as cell adhesion molecules has not been studied, although they are heavily involved in cardiovascular diseases’ (CVDs) processes. The aim of our study was then to investigate a possible sex-specific effect of the GNB3 C825T polymorphism on serum soluble cell adhesion molecules such as E, P and L-selectins (sE, sP and sL-selectins).ResultsParticipants were from the STANISLAS Family Study and were free of chronic disease as CVDs or cancer. We included in total 771 subjects aged 6 to 58 years (391 males (50.71%) and 380 females (49.29%)). No significant association of rs5443 was observed in the whole population with serum sE, sP and sL-selectins after adjusting for age, sex, body mass index, systolic blood pressure, anti-inflammatory drugs and hormonal drugs consumption. A significant interaction of rs5443 was observed with sex for sE-selectin (p < 0.001), but not for sP and sL-selectins. After adjusting for covariables, the T allele was significantly associated with an additive increase effect on serum sE-selectin levels in males (β = 5.03 ± 2.18; p = 0.020), while a significant additive decrease effect was observed in females (β =−4.46 ± 2.06; p = 0.030). These associations stayed significant after correction for multiple tests (p = 0.045 in males and in females). The additive phenotypic variance was 21.54% in males versus 1.91% in females.ConclusionsIn our Caucasian population, the GNB3 C825T polymorphism showed a significant sex-specific effect on serum sE-selectin levels, with a disadvantage for males, as increased sE-selectin levels has been associated with CVDs outcomes. The T allele has been previously associated with the same CVDs as increased sE-selectin, but more often in males. The link we observed between this polymorphism and E-selectin is then consistent with previous findings, and helps to better understand the deleterious effect of the GNB3 825 T allele on CVDs outcomes in males. We revealed in this study an important pathway through which the GNB3 gene induces CVDs’ outcomes.

Endotelial activation and flow-mediated vasodilation in young patients with breast cancer

Endothelial activation and dysfunction may play a significant role in the progression of breast cancer. In our study we examined markers of endothelial activation (soluble ICAM-1, P-selectin, E-selectin) in 98 young patients with breast cancer (< 40 years). In 50 of them (and 20 age-matched controls) we also measured flow mediated vasodilation. Patients with breast cancer had significantly higher serum levels of soluble E-selectin, P-selectin and ICAM-1, P-selectin was higher in patients with larger tumors, node involvement and seemed to be apredictor of poor outcome. We were unable to find significant difference in the parameters of flow mediated vasodilation between patients with breast cancer and healthy subjects, although both peak blood flow (PBF) and flow mediated vasodilation (FMD) seemed to be skewed compared to healthy subjects toward mean and lower levels. Cluster analysis enabled us to distinguish several larger groups of patients with different degree of endothelial activation and function and different outcome. Group of patients with high E-selectin, high ICAM-1 (higher endothelial activation) and low VEGF (putative endothelial damage) had more frequently negative estrogen receptors and had worse outcome compared to the group of patients with lower E-selectin, lower ICAM-1 and mostly positive estrogen receptors. Further studies of larger groups of patients should help to identify the panel of endothelial markers which could help in predicting the outcome of young patients with breast cancer.

Assessment of the E-selectin rs5361 (561A>C) polymorphism and soluble protein concentration in acute coronary syndrome: association with circulating levels.

Introduction. The acute coronary syndrome (ACS) is a complex disease where genetic and environmental factors are involved. E-selectin gene is a candidate for ACS progression due to its contribution in the inflammatory process and endothelial function. The rs5361 (561A>C) polymorphism in the E-selectin gene has been linked to changes in gene expression, affinity for its receptor, and plasmatic levels; therefore it is associated with an increased risk of cardiovascular disease. The aim of this study was to determine the association of the rs5361 polymorphism with ACS and to measure serum levels of soluble E-selectin (sE-selectin). Materials and Methods. 283 ACS patients and 205 healthy subjects (HS) from Western Mexico were included. The polymerase chain reaction-restriction fragment length polymorphism was used to determine the rs5361 polymorphism. The sE-selectin levels were measured by enzyme-linked immunosorbent assay. Results. Neither genotype nor allele frequencies of the rs5361 polymorphism showed statistical differences between groups. The sE-selectin levels were significantly higher in ACS patients compared to HS (54.58 versus 40.41 ng/ml, P = 0.02). The C allele had no effect on sE-selectin levels. Conclusions. The rs5361 E-selectin gene polymorphism is not a susceptibility marker for ACS in Western Mexico population. However, sE-selectin may be a biological marker of ACS.

Circulating sICAM-1 and sE-Selectin as biomarker of infection and prognosis in patients with systemic inflammatory response syndrome

BackgroundVascular endothelium activation is a key pathogenic step in systemic inflammatory response syndrome (SIRS) that can be triggered by both microbial and sterile proinflammatory stimuli. The relevance of soluble adhesion molecules as clinical biomarkers to discriminate between infectious and non-infectious SIRS, and the individual patient prognosis, has not been established. MethodsWe prospectively measured by sandwich ELISA, serum levels of soluble E-Selectin (sE-Selectin), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1 (sICAM-1) and soluble intercellular adhesion molecule-2 (sICAM-2) at ICU admission and at days 3, 7, 14 and 28 in patients with sepsis and at days 3 and 7 in patients with non-infectious SIRS. ResultsAt ICU admission, sE-Selectin, sVCAM-1 and sICAM-1 in patients with infectious SIRS were significantly higher than those found in patients with non-infectious SIRS. ROC analysis revealed that the AUC for infection identification was best for sICAM-1 (0.900±0.041; 95% CI 0.819-0.981; p<0.0001). Moreover, multivariate analysis showed that 4 variables were significantly and independently associated with mortality at 28days: male gender (OR 15.90; 95% CI, 2.54–99.32), MODS score (OR 5.60; 95% CI, 1.67–18.74), circulating sE-Selectin levels (OR 4.81; 95% CI, 1.34–17.19) and sVCAM-1 concentrations (OR 4.80; 95% CI, 1.34–17.14). ConclusionsPatients with SIRS secondary to infectious or non-infectious etiology show distinctive patterns of disturbance in serum soluble adhesion molecules. Serum ICAM-1 is a reliable biomarker for classifying patients with infectious SIRS from those with non-infectious SIRS. In addition, soluble E-Selectin is a prognostic biomarker with higher levels in patients with SIRS and fatal outcome.

Early systemic sclerosis: marker autoantibodies and videocapillaroscopy patterns are each associated with distinct clinical, functional and cellular activation markers

IntroductionEarly systemic sclerosis (SSc) is characterized by Raynaud's phenomenon together with scleroderma marker autoantibodies and/or a scleroderma pattern at capillaroscopy and no other distinctive feature of SSc. Patients presenting with marker autoantibodies plus a capillaroscopic scleroderma pattern seem to evolve into definite SSc more frequently than patients with either feature. Whether early SSc patients with only marker autoantibodies or capillaroscopic positivity differ in any aspect at presentation is unclear.MethodsSeventy-one consecutive early SSc patients were investigated for preclinical cardiopulmonary alterations. Out of these, 44 patients and 25 controls affected by osteoarthritis or primary fibromyalgia syndrome were also investigated for serum markers of fibroblast (carboxyterminal propeptide of collagen I), endothelial (soluble E-selectin) and T-cell (soluble IL-2 receptor alpha) activation.ResultsThirty-two of the 71 patients (45.1%) had both a marker autoantibody and a capillaroscopic scleroderma pattern (subset 1), 16 patients (22.5%) had only a marker autoantibody (subset 2), and 23 patients (32.4%) had only a capillaroscopic scleroderma pattern (subset 3). Patients with marker autoantibodies (n = 48, 67.6%) had a higher prevalence of impaired diffusing lung capacity for carbon monoxide (P = 0.0217) and increased serum levels of carboxyterminal propeptide of collagen I (P = 0.0037), regardless of capillaroscopic alterations. Patients with a capillaroscopic scleroderma pattern (n = 55, 77.5%) had a higher prevalence of puffy fingers (P = 0.0001) and increased serum levels of soluble E-selectin (P = 0.0003) regardless of marker autoantibodies.ConclusionThese results suggest that the autoantibody and microvascular patterns in early SSc may each be related to different clinical-preclinical features and circulating activation markers at presentation. Longitudinal studies are warranted to investigate whether these subsets undergo a different disease course over time.

Endothelial Cell Function in Patients with Hereditary Angioedema: Elevated Soluble E-selectin Level During Inter-attack Periods

The bradykinin pathway in the pathomechanism of hereditary angioedema due to C1-inhibitor deficiency (henceforward "hereditary angioedema") has been thoroughly studied; however, much less is known about endothelial cell function. Enhanced endothelial cell permeability is obvious during edematous attacks, but not during inter-attack periods. Our knowledge about other endothelial characteristics is even more incomplete. Therefore the aim of this study was to characterize endothelial cell function in hereditary angioedema patients during symptom-free, inter-attack periods. We measured the serum levels of soluble E-selectin, endothelin-1, and von Willebrand factor along with collagen-binding activity in 49 hereditary angioedema patients and in 50 healthy controls. Endothelin-1 and von Willebrand factor level, as well as its collagen-binding activity, were similar in hereditary angioedema patients and in controls; however, we found elevated soluble E-selectin levels in the patients. Interestingly, soluble E-selectin concentration did not correlate with any of the inflammatory markers or smoking, and it is not the consequence of the known E-selectin/C1-inhibitor interaction (an analytical phenomenon). In a multiple logistic regression model, the difference in soluble E-selectin between hereditary angioedema patients and controls remained highly significant when adjusted for age, gender, smoking, C-reactive protein, and AB0 blood groups. These results demonstrate that in hereditary angioedema, the majority of endothelial functions are normal during inter-attack periods; however, soluble E-selectin levels are elevated. The higher soluble E-selectin plasma concentration is unlikely to result from inflammation; rather, it reflects enhanced shedding mechanisms.

Genome-Wide Association Identifies the ABO Blood Group as a Major Locus Associated With Serum Levels of Soluble E-Selectin

Elevated serum soluble E-selectin levels have been associated with a number of diseases. Although E-selectin levels are heritable, little is known about the specific genetic factors involved. E-selectin levels have been associated with the ABO blood group phenotype. We performed a high-resolution genome-wide association study of serum soluble E-selectin levels in 685 white individuals with type 1 diabetes from the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Intervention and Complications (EDIC) study to identify major loci influencing levels. Highly significant evidence for association (P=10(-29)) was observed for rs579459 near the ABO blood group gene, accounting for 19% of the variance in E-selectin levels. Levels of E-selectin were higher in O/O than O/A heterozygotes, which were likewise higher than A/A genotypes. Analysis of subgroups of A alleles reveals heterogeneity in the association, and even after this was accounted for, an intron 1 SNP remained significantly associated. We replicate the ABO association in nondiabetic individuals. ABO is a major locus for serum soluble E-selectin levels. We excluded population stratification, fine-mapped the association to sub-A alleles, and also document association with additional variation in the ABO region.

E-selectin S128R polymorphism leads to severe asthma.

The E-selectin mediates the interaction of activated endothelial cells with leukocytes and plays a fundamental role in the pathogenesis of asthma. It has been suggested that an S/R (Serine128Arginine) polymorphism of E-selectin alters ligand binding function. Our purpose in this study was to determine whether this Serine128Arginine polymorphism influences the risk of asthma and also to analyze the possible correlation of disease severity in Iranian patients with polymorphism of E-selection. We studied human E-selectin gene polymorphism in 172 asthmatic patients and 173 healthy volunteers by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). To determine the severity of the asthma's situation, a questionnaire was prepared requesting the following information: age, sex, clinical signs and symptoms and past medical history. After the participants filled in the questionnaire, all active or ex-smoker patients were excluded. A trained observer assessed airway reversibility, peak flowmetry and spirometry in asthmatic patients. We found increased serum levels of soluble E-selectin (sE-selectin) in asthmatic patients compared with healthy subjects (P<0. 0001). Frequencies of the SS, SR, and RR genotypes were found as 66.3%, 31.4%, and 2.3% in the patients and 91.9%, 8.1%, and 0.0% in control subjects, respectively. The 128Arg allele was more prevalent in patients than controls (OR 5.78; 95% CI, 3.07-10.86, P<0.0001). However, in this study the polymorphism was not associated with circulating sE-selectin levels. We found a direct correlation between the level of sE-selectin and the severity of asthma (P=0.001). On the other hand, there was a close relation between 128Arginine carriage and disease severity (P<0.0001). These results suggest that the Ser128Arg polymorphism of the E-selectin gene is a genetic factor that may be associated with the severity of asthma.

Periodontal infection profiles in type 1 diabetes

We investigated the levels of subgingival plaque bacteria and serum IgG responses in patients with type 1 diabetes and non-diabetic controls of comparable periodontal status. Fifty type 1 diabetes patients (mean duration 20.3 years, range 6-41) were age-and gender-matched with 50 non-diabetic individuals with similar levels of periodontal disease. Full-mouth clinical periodontal status was recorded, and eight plaque samples/person were collected and analysed by checkerboard hybridization with respect to 12 species. Homologous serum IgG titres were assessed by checkerboard immunoblotting. In a sub-sample of pairs, serum cytokines and selected markers of cardiovascular risk were assessed using multiplex technology. Among the investigated species, only levels of Eubacterium nodatum were found to be higher in diabetic patients, while none of the IgG titres differed between the groups, both before and after adjustments for microbial load. Patients with diabetes had significantly higher serum levels of soluble E-selectin (p=0.04), vascular cell adhesion molecule-1 (VCAM-1; p=0.0008), adiponectin (p=0.01) and lower levels of plasminogen activator inhibitor-1 (PAI-1; p=0.02). After controlling for the severity of periodontal disease, patients with type 1 diabetes and non-diabetic controls showed comparable subgingival infection patterns and serum antibody responses.

Gene Expression of E-Selectin in Tissue and its Protein Level in Serum of Breast Cancer Patients

This study aims to detect the expression of E-selectin in tissue and the serum level of its soluble form in patients with primary breast cancer and benign breast tumors and to correlate the results with the clinicopathological data of the subjects. Fifty participants were included in the study and stratified into 3 subgroups. Group A comprised 30 patients with primary breast cancer, group B 9 patients with benign breast tumors, and group C 11 healthy control women undergoing reduction mammoplasty. E-selectin gene expression was investigated in breast tissues by PCR techniques and soluble E-selectin was measured in sera by ELISA. The E-selectin gene was expressed in 73.3% of group A, 44.4% of group B and 9.1% of group C. It was expressed in 61.5% of patients with grade 2 breast cancer and in 82.4% of patients with grade 3 breast cancer. E-selectin gene expression was detected in 60%, 73.3% and 100% of patients with stage II, III and IV tumors, respectively. It was detected in 81.8% of patients with node-positive primary breast cancer and in 50% of patients with node-negative cancer. PCR in situ hybridization was done to locate the site of E-selectin expression. E-selectin was found on the membranes of peritumoral endothelial cells while it was not found on breast epithelial cells. Serum levels of soluble E-selectin were significantly elevated in group A compared to groups B and C (P < 0.001). They increased significantly with increasing breast cancer stage (P < 0.001) and were significantly higher in patients with lymph node involvement than in patients without node involvement (P < 0.001). The studied marker showed associations with established prognostic parameters such as lymph node involvement and histological tumor grade. Further studies are needed to evaluate E-selectin as a possible target for antimetastatic therapy through modulation of the expression of the cell adhesion molecule. E-selectin can be regarded as a promising strategy in improving tumor therapy.

Cutaneous Endothelial Cell Activation in Normal Skin of Patients with Dermatitis Herpetiformis Associated with Increased Serum Levels of IL-8, sE-Selectin, and TNF-α

The mechanisms that lead to the development of skin lesions in patients with dermatitis herpetiformis (DH) are not known. We hypothesized that an ongoing immune response in the gut of patients with DH would result in an increase in circulating cytokines and be associated with endothelial cell activation, creating a proinflammatory environment in the skin. Skin biopsies from the normal-appearing inner arm of 11 DH patients, with no active skin lesions, and 12 normal subjects were analyzed for E-selectin (E-sel) and ICAM-1 mRNA. DH patients' skin expressed markedly increased levels of E-sel mRNA. Mean E-sel mRNA expression in DH skin was 1,271 (range 63.78-5861) times greater than that of a control, normal skin (P<0.001) with no significant increased expression of ICAM-1 mRNA. Serum levels of soluble E-selectin (sE-sel), IgA anti-tissue transglutaminase antibodies, and serum IL-8 levels were significantly increased in patients with DH. These studies demonstrate that patients with DH have evidence of endothelial cell activation in the skin and systemic manifestations of the ongoing inflammation associated with the mucosal immune response. Endothelial cell activation may play a critical role in the development of skin lesions in patients with DH and may represent a common mechanism for cutaneous manifestations of inflammatory gastrointestinal diseases.

Dietary Whey Protein Hydrolysate Suppresses Development of Atopic Dermatitis-like Skin Lesions Induced by Mite Antigen in NC/Nga Mice

Oral administration of enzymatic hydrolysate of cow's milk whey protein (WPH) has been reported to produce an anti-inflammatory effect. Since inflammation plays a role in dermatitis of allergic disease, we examined the influence of WPH on the development of atopic dermatitis (AD)-like skin lesions, induced in NC/Nga mice by the mite antigen Dermatophagoides pteronyssinus (Dp). AD-like skin lesions were induced on the pinnae and backs of NC/Nga mice by daily application of Dp for 4 weeks. Mice were fed cow's milk casein (control), WPH or casein protein hydrolysate (CPH) diets for 2 weeks prior to Dp application. Clinical skin conditions were evaluated periodically by a clinical severity score, total serum IgE and soluble E-selectin levels were measured by enzyme linked immunosorbent assay (ELISA). WPH-fed mice showed significantly less AD-like skin lesions than those fed casein diets at 2 and 4 weeks after Dp application. In contrast, CPH-fed mice had manifestations in a similar manner as casein-fed mice did, and did not show an inhibitory effect. Serum soluble E-selectin levels, known as a marker of disease activity in AD patients, were significantly lower in the WPH diet group. Our results suggest that in addition to its hypoallergenicity an anti-inflammatory function, dietary WPH might be useful for reducing the severity of AD-like skin lesions.

Identification and characterization of the carboxy-terminal region of Sip-1, a novel autoantigen in Behçet's disease

Given the lack of a serological test specific for Behçet's disease, its diagnosis rests upon clinical criteria. The clinical diagnosis is nevertheless difficult because the disease manifestations vary widely, especially at the onset of disease. The aim of this study was to identify molecules specifically recognized by serum autoantibodies in patients with Behçet's disease and to evaluate their diagnostic value. We screened a cDNA library from human microvascular endothelial cells with serum IgG from two patients with Behçet's disease and isolated a reactive clone specific to the carboxy-terminal subunit of Sip1 (Sip1 C-ter). Using ELISA, we measured IgG, IgM and IgA specific to Sip1 C-ter in patients with various autoimmune diseases characterized by the presence of serum anti-endothelial cell antibodies, such as Behçet's disease, systemic lupus erythematosus, systemic sclerosis and various forms of primary vasculitis, as well as in patients with diseases that share clinical features with Behçet's disease, such as inflammatory bowel disease and uveitis. IgM immunoreactivity to Sip1 C-ter was significantly higher in patients with Behçet's disease and in patients with primary vasculitis than in the other groups of patients and healthy subjects tested (P < 10-4 by Mann-Whitney test). ELISA detected IgG specific to Sip1 C-ter in sera from 11/56 (20%) patients with Behçet's disease, IgM in 23/56 (41%) and IgA in 9/54 (17%). No sera from patients with systemic lupus erythematosus, systemic sclerosis, inflammatory bowel disease, uveitis or healthy subjects but 45% of sera from patients with primary vasculitis contained IgM specific to Sip1 C-ter. Serum levels of soluble E-selectin, a marker of endothelial activation and inflammation, correlated with levels of serum IgM anti Sip-1 C-ter in patients with Behçet's disease (r = 0.36, P = 0.023). In conclusion, Sip1 C-ter is a novel autoantigen in Behçet's disease. IgM specific to Sip1 C-ter might be useful in clinical practice as an immunological marker of endothelial dysfunction in vasculitis.

Association of mineral metabolism with an increase in cellular adhesion molecules: another link to cardiovascular risk in maintenance haemodialysis?

Abnormal mineral metabolism is associated with increased cardiovascular morbidity and mortality. The exact pathogenesis linking mineral metabolism to cardiovascular risk is unknown. This study was undertaken to investigate the association between serum phosphate and/or Ca x PO(4) product with serum levels of soluble E-selectin (sE-selectin), soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 and the degree of carotid artery atherosclerosis in patients on haemodialysis. Seventy-three patients (46 male, 27 female; mean age 48+/-13 years, on haemodialysis for 82+/-80 months) were included in the study. All patients were stable, had no evidence of vascular disease and/or active infection. Consecutive 6 months clinical and laboratory data were obtained for each patient from their medical records and mean values were used for analysis. Serum levels of soluble adhesion molecules were assayed by ELISA. All subjects underwent a detailed evaluation of the carotid arteries. The percentage of patients who met all three targets of NKF-K/DOQI for phosphate, calcium and Ca x PO(4) product was 27.1%, whereas those who did not achieve the target in one, two or three parameters was 28.1, 17.7 and 14.6%, respectively. The sICAM-1 levels were significantly higher in patients who had hyperphosphataemia (serum phosphate >5.5 mg/dl; P = 0.044) and hypercalcaemia (serum calcium >9.5 mg/dl; P = 0.014), both sE-selectin and sICAM-1 levels were significantly higher in patients with Ca x PO(4) product levels above 55 mg(2)/dl(2) (P = 0.002 and P = 0.000, respectively). Soluble E-selectin and sICAM levels demonstrated a near-linear increase in parallel to the degree of deviation from mineral metabolism targets. Soluble E-selectin and sICAM levels were correlated with serum phosphate and Ca x PO(4) product, but there were no correlations between adhesion molecules and carotid measurements. These findings suggest that in stable haemodialysis patients abnormal bone mineral metabolism was associated with increased soluble adhesion molecules. These alterations in adhesion molecules may favour the development of cardiovascular changes and contribute to high cardiovascular morbidity and mortality in patients with abnormal mineral metabolism.

Reduction of Soluble E-Selectin after Combined Treatment with Simvastatin and Vitamins C and E

Objective: We investigated the influence of treatment with simvastatin and vitamins C and E on serum levels of soluble cell adhesion molecules (sCAM) as markers of atherosclerosis and endothelial activation. Methods: In 11 hypercholesterolemic patients, serum levels of sCAM were measured by enzyme immunoassay before and after 6 weeks of treatment with either simvastatin (20 mg) or vitamin C (1 g) plus vitamin E (600 mg) and after an additional 6 weeks of combined treatment. In 8 of the patients angiography was performed at study entry. Results: Baseline levels of soluble intercellular adhesion molecule-1 (sICAM-1) showed an age-dependent increase (coefficient of correlation 0.71, p = 0.014) and were higher in patients with established atherosclerotic lesions than in patients with no such lesions (369.5 ± 61.8 vs. 238.4 ± 56.4 ng/ml, p = 0.023). Whereas either treatment alone had no influence on the serum levels of sCAM, combined treatment with simvastatin and vitamins C and E reduced serum levels of soluble E-selectin from 43.2 ± 18.9 ng/ml at baseline to 39.7 ± 16.5 ng/ml (p = 0.027) at study end. Although not significant, levels of soluble P-selectin were also reduced from a mean of 125.9 ± 64.1 ng/ml at baseline to 115 ± 64.9 ng/ml (p = 0.1). Serum levels of sICAM-1 and soluble vascular cell adhesion molecule-1 (sVCAM-1) remained unchanged by this treatment. Conclusion: Combined treatment with simvastatin and vitamins C and E reduced serum levels of soluble E-selectin but had no influence on sICAM-1 and sVCAM-1 levels.

Elevation of Serum Soluble E- and P-Selectin in Patients with Hypertension Is Reversed by Benidipine, a Long-Acting Calcium Channel Blocker

Hypertension is a major risk factor for atherosclerotic cardiovascular disease. Selectins, cell-surface adhesion molecules involved in leukocyte rolling and attachment to the vascular endothelium, play a role in the initiation of atherosclerosis. We investigated whether or not serum levels of soluble adhesion molecules are elevated in patients with essential hypertension (EH) and examined whether antihypertensive therapy lowers such levels. Twenty-one patients who had untreated mild to moderate EH without diabetes mellitus, hyperlipidemia, or obesity were recruited at a clinic for hypertensive patients. Blood pressure was measured, and the serum levels of soluble E-selectin, P-selectin, L-selectin, intercellular adhesion molecule 1 (ICAM-1), and vascular-cell adhesion molecule 1 (VCAM-1) were determined by enzyme-linked immunosorbent assays before and after 12, 24, and 53 weeks of antihypertensive treatment with benidipine, a long-acting calcium channel blocker, given at a dose of 6 mg/day for 53 weeks. As a control, 21 age- and sex-matched patients without hypertension were studied. Serum E- and P-selectin levels were significantly higher in the subjects with EH than in the controls (p < 0.01). There were no differences in serum levels of soluble L-selectin, VCAM-1, or ICAM-1 levels between the patients with EH and the controls. Treatment with benidipine decreased the elevated blood pressure over a 53-week study period (mean blood pressure: 119.8 +/- 6.5 mmHg at baseline, 101.0 +/- 5.9 mmHg at 12 weeks, 98.6 +/- 7.3 mmHg at 24 weeks, and 93.9 +/- 5.5 mmHg at 53 weeks). Serum levels of soluble E- and P-selectin decreased after the initiation of benidipine treatment and correlated with diastolic blood pressure. Serum levels of soluble L-selectin, VCAM-1, and ICAM-1 did not change significantly during the period of benidipine treatment. Benidipine treatment reduced the content of P-selectin in the platelets from patients with EH, as determined by Western blot analysis. In conclusion, decreased blood pressure may reduce the rate of progression of atherosclerosis by affecting the expression of E- and P-selectin in the endothelium, the platelets, or both. Benidipine may be protective against vascular damage in people with hypertension, not only by lowering blood pressure, but also by inhibiting the expression of selectins.

Circulating adhesion molecules levels in type 2 diabetes mellitus and hypertension

Background: Risk factors for atherosclerosis such as hypertension, type 2 diabetes, obesity and dyslipidemia affect endothelial function and stimulate adhesion molecules expression. The aim of the study was to examine endothelial activation in type 2 diabetes and hypertension as indicated by adhesion molecule levels and further to investigate whether the coexistence of the above conditions has a different effect. Methods: Serum levels of soluble E-selectin, ICAM-1 and VCAM-1 were measured in 17 hypertensive type 2 diabetic patients (DM-HY), 32 normotensive type 2 diabetic patients (DM), 11 hypertensive nondiabetic patients (HY) and 15 healthy subjects. Results: In diabetic patients (either DM-HY or DM), soluble E-selectin levels were significantly increased compared to healthy subjects ( p<0.001). In HY patients, both sE-selectin (66.44±71.59 vs. 29.42±15.56 ng/ml, p=0.033) and sVCAM-1 (1529±433.33 vs. 1027±243.56 ng/ml, p=0.03) levels were found significantly higher compared to healthy subjects ( p<0.05). The coexistence of diabetes and hypertension (DM-HY) did not have an additive effect on circulating adhesion molecules levels compared with the levels observed in either diabetes or hypertension. Systolic and diastolic blood pressure (BP) were independent factors correlated respectively with sE-selectin and sVCAM-1 levels ( R=0.454, p=0.034 and R=0.578, p=0.005) in nondiabetic subjects (hypertensive and normotensive). Conclusions: Type 2 diabetes mellitus and hypertension induce endothelial activation as indicated by elevated levels of soluble adhesion molecules. This effect is not different when comorbidity is present.