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З метою вивчення рівня судинної молекули міжклітинної адгезії-1 (sVCAM-1) у дітей із бронхіальною астмою на різних етапах захворювання нами обстежено 69 дітей віком від 6 до 17 років, які страждають від персистуючої бронхіальної астми, в період загострення та ремісії та 15 практично здорових дітей групи контролю. Проводили манжетову пробу та визначали рівень S-нітрозотіолу в сироватці крові для оцінки функції ендотелію. Вивчали рівень sVCAM-1 у сироватці крові імуноферментним методом. Установлено наявність ендотеліальної дисфункції у всіх дітей, хворих на бронхіальну астму. Відмічено значне підвищення рівня sVCAM-1 у сироватці крові як у період загострення, так і в період ремісії захворювання, що свідчить про триваючий вплив на ендотелій та формування стійкого хронічного запалення.

Summary Increasing evidence suggests that free haem and iron exert vasculo‐toxic and pro‐inflammatory effects by activating endothelial and immune cells. In the present retrospective study, we compared serum samples from transfusion‐dependent patients with β‐thalassaemia major and intermedia, hereditary spherocytosis and sickle cell disease (SCD). Haemolysis, transfusions and ineffective erythropoiesis contribute to haem and iron overload in haemolytic patients. In all cohorts we observed increased systemic haem and iron levels associated with scavenger depletion and toxic ‘free’ species formation. Endothelial dysfunction, oxidative stress and inflammation markers were significantly increased compared to healthy donors. In multivariable logistic regression analysis, oxidative stress markers remained significantly associated with both haem‐ and iron‐related parameters, while soluble vascular cell adhesion molecule 1 (sVCAM‐1), soluble endothelial selectin (sE‐selectin) and tumour necrosis factor α (TNFα) showed the strongest association with haem‐related parameters and soluble intercellular adhesion molecule 1 (sICAM‐1), sVCAM‐1, interleukin 6 (IL‐6) and vascular endothelial growth factor (VEGF) with iron‐related parameters. While hereditary spherocytosis was associated with the highest IL‐6 and TNFα levels, β‐thalassaemia major showed limited inflammation compared to SCD. The sVCAM1 increase was significantly lower in patients with SCD receiving exchange compared to simple transfusions. The present results support the involvement of free haem/iron species in the pathogenesis of vascular dysfunction and sterile inflammation in haemolytic diseases, irrespective of the underlying haemolytic mechanism, and highlight the potential therapeutic benefit of iron/haem scavenging therapies in these conditions.

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.

Background/aim Radiotherapy (RT) can lead to cardiovascular disease (CVD). Evidence suggests that radiation modulates miRNA levels. Our purpose was to assess the acute response to radiation-induced modulation of the expression of miRNA-146a, miRNA-155, miRNA-221, and miRNA-222, inflammatory response and endothelial dysfunction on endothelial cells. Materials and methods Human umbilical vein endothelial cells (HUVECs) were exposed to 2 Gy RT, and intracellular levels of selected miRNAs were measured by real-time polymerase chain reaction at 2 and 24 h. Cytokine and adhesion molecule release were also assessed. Results Results showed that 2 Gy significantly increased the expression of miRNA-221 and miRNA-222, and reduced the level of miRNA-155 after 2 h; whereas miRNA-146a and miRNA-155 were significantly overexpressed and miRNA-222 was significantly down-regulated at 24 h. Interleukin-8 and soluble vascular cell adhesion molecule 1 levels were not affected by the studied RT. Conclusion RT at 2 Gy modulated expression of selected miRNAs by endothelial cells after 2 and 24 h, which might be related to CVD development in patients who receive RT.

The aim of the present study was to explore whether there is enhanced endothelial dysfunction in patients developing acute GvHD (aGvHD) after allogeneic hematopoietic cell transplantation (allo-HCT) and to identify biomarkers with predictive and/or diagnostic value. In in vitro experiments, endothelial cells (ECs) were exposed to serum from patients with (aGvHD, n = 31) and without (NoGvHD, n = 13) aGvHD, to evaluate changes in surface adhesion receptors, the reactivity of the extracellular matrix by measuring the presence of Von Willebrand factor (VWF) and platelet adhesion, and the activation of intracellular signaling proteins. Plasma levels of VWF, ADAMTS-13, TNF receptor 1 (TNFR1), soluble vascular cell adhesion molecule 1 and soluble intercellular adhesion molecule 1 were also measured. In vitro results showed a more marked proinflammatory and prothrombotic phenotype in ECs in association with aGvHD. Regarding circulating biomarkers, levels of VWF and TNFR1 above an optimal cutoff score, taken independently or combined, at day 7 after allo-HCT, would be able to positively predict that around 90% of patients will develop aGvHD. Our results demonstrate that endothelial damage is aggravated in those allo-HCT recipients developing aGvHD, and that VWF and TNFR1 are promising predictive aGvHD biomarkers. These findings could contribute to improve the understanding of the pathophysiology of aGvHD.

BackgroundEndothelial 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.MethodsA 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, 1 h after placental separation, and 24 h postpartum. sVCAM-1 and blood pressure levels were determined.ResultsThe 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 t...

INTRODUCTION Little is known about the CD40L-CD40 pathway in hematologic malignancies, especially in multiple myeloma (MM). OBJECTIVES The aim of the current study was to evaluate serum soluble CD40 ligand (sCD40L) concentrations in patients with newly diagnosed MM prior to treatment at different stages of disease, compared with healthy controls. To assess the clinical significance of sCD40L, we assessed correlations between the levels of sCD40L and those of angiogenic cytokines: interleukin 6 (IL-6), soluble receptor of IL-6 (sIL-6R), tumor necrosis factor α (TNF-α), soluble vascular cell adhesion molecule 1 (sVCAM-1), and platelet-derived growth factor AB (PDGF-AB), as well as with well-established biomarkers of MM activity (lactate dehydrogenase activity and percentage of bone marrow plasma cells) and with a marker of platelet activation (β-thromboglobulin). PATIENTS AND METHODS The study group consisted of 41 patients with newly diagnosed MM; the control group consisted of 30 healthy subjects. The level of sCD40L was determined using an enzyme-linked immunosorbent assay. RESULTS The level of sCD40L was significantly higher in patients with MM than in controls and increased with the stage of the disease. Moreover, it significantly correlated with the levels of IL-6, sIL-6R, sVCAM-1, PDGF-AB, as well as the levels of MM activity markers and β-thromboglobulin. CONCLUSIONS Our findings indicate that increased serum sCD40L levels may be related to angiogenesis in patients with MM. This protein has potential clinical usefulness in MM and may be considered as an additional prognostic marker. The correlation of sCD40L with β-thromboglobulin may indicate that in patients with MM sCD40L derives from activated platelets.

Background. The relationship between inflammation and coagulation has been widely described, which adhesion molecules play important role in inflammation. Soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) seem to be related to thrombosis in few previous studies. The level of those molecules were increased in mitral stenosis (MS), however their relationship with left atrial thrombosis gradation is still unknown. Methods. Patients with moderate-severe MS (without any significant mitral regurgitation) who underwent transesophageal echocardiography were recruited consecutively in September-October 2013. They were divided into 3 categories of left atrial thrombosis gradation: non-thrombus without dense left atrial spontaneous echo contrast (LASEC) group, and non-thrombus with dense LASEC group, and thrombus group. Results. A total of 39 subjects were enrolled in the study with a mean age of 40.979.61 year. Moreover, 71.8% of them were female and 67.7% of them had atrial fibrillation (AF). Evaluation on left atrial thrombosis gradation as mentioned above showed that sICAM-1 levels were 284.74 (218.79-321.00) ng/mL, 346.86 (125.68-698.12) ng/mL, and 395.93 (171.44-1021.53) ng/mL, consecutively (p=0.280). While sVCAM-1 levels gradually increased based on those groups consecutively: 729.01 (543.93-967.80) ng/mL, 1066.00 (581.36-2470.60) ng/mL, and 1158.00 (668.66-2498.30) ng/mL (p=0.016). Multivariate analysis showed that AF and mitral valve area (MVA) influence thrombosis gradation. Conclusion. Difference in sVCAM-1 levels were found among left atrial thrombosis gradation groups in mitral stenosis, but its effect on thrombosis gradation was influenced by AF and MVA.

Endothelial dysfunction has been implicated in the pathogenesis of atherosclerosis. Salvia miltiorrhiza (danshen) is a traditional Chinese medicine that has been effectively used to treat cardiovascular disease. Cryptotanshinone (CTS), a major lipophilic compound isolated from S. miltiorrhiza, has been reported to possess cardioprotective effects. However, the anti-atherogenic effects of CTS, particularly on tumor necrosis factor-α (TNF-α)-induced endothelial cell activation, are still unclear. This study aimed to determine the effect of CTS on TNF-α-induced increased endothelial permeability, monocyte adhesion, soluble intercellular adhesion molecule 1 (sICAM-1), soluble vascular cell adhesion molecule 1 (sVCAM-1), monocyte chemoattractant protein 1 (MCP-1) and impaired nitric oxide production in human umbilical vein endothelial cells (HUVECs), all of which are early events occurring in atherogenesis. We showed that CTS significantly suppressed TNF-α-induced increased endothelial permeability, monocyte adhesion, sICAM-1, sVCAM-1 and MCP-1, and restored nitric oxide production. These observations suggest that CTS possesses anti-inflammatory properties and could be a promising treatment for the prevention of cytokine-induced early atherogenesis.

Objective. Antinuclear antibodies (ANA) serve as screening tests for connective tissue diseases but have low specificity. In this pilot study, we aimed to identify patients with first-time positive ANA and musculoskeletal complaints and correlate serum soluble vascular adhesion molecules as biomarkers. Methods. Prospective, observational study with 100 ANA-positive patients, comparing them to age- and gender-matched healthy controls (HC, n=75), was conducted. Serum levels of soluble intercellular adhesion molecule-1 (sICAM-1), endothelial-leukocyte adhesion molecule-1 (sELAM-1), and vascular cell adhesion molecule-1 (sVCAM-1) were measured. A subgroup of patients with systemic sclerosis (SSc) treated with immunosuppressants was followed over 10 months. Results. Patients belonged to three main entities: rheumatoid arthritis (RA, n=32), collagen diseases (CD, n=56) also including systemic sclerosis (SSc, n=11), and other autoimmune diseases (n=12). sICAM-1 was similar among groups. sELAM-1 was elevated by 1.9-fold in only in SSc. sVCAM-1 was elevated by 3.1-fold in RA and by 3.3-fold in CD and in other autoimmune diseases by 3.4-fold. Seven SSc patients with immunosuppression had a 2.7-fold increased sVCAM-1 at baseline and reached the levels of healthy controls after 5 months, while CRP, ESR, and clinical parameters remained unchanged. Conclusion. Our study suggests that sVCAM-1 is a disease marker independent of standard serum parameters in several rheumatic diseases. This study is registered with EU PAS Register number: EUPAS22154.

Background/Objective: This study was performed to compare soluble levels of adhesion molecules between diabetic patients and controls and to assess their possible association with long-term complications of type 1 diabetes (T1D). Methods: Forty-eight patients with T1D and 39 healthy controls were enrolled in this study. The plasma level of adhesion molecules was measured by sandwich enzyme-linked immunosorbent assay technique. Results: Higher sVCAM 1 (soluble vascular cell adhesion molecule 1) levels correlated with older age of onset of T1D. The plasma level of sICAM 1 (soluble intercellular adhesion molecule 1) was significantly increased, while sE selectin was significantly decreased in patients with T1D, compared to controls. There was no significant relationship between these plasma-level variations and the long-term complications of T1D. Conclusion: Although plasma levels of cell adhesion molecules are different in T1D patients and healthy controls, they might not be good candidate markers f...

Objective: To evaluate five biomarkers (neopterin, vascular endothelial growth factor-A, thrombomodulin, soluble vascular cell adhesion molecule 1 and pentraxin 3) in differentiating clinical dengue cases. Methods: A prospective cohort study was conducted whereby the blood samples were obtained at day of presentation and the final diagnosis were obtained at the end of patients’ follow-up. All patients included in the study were 15 years old or older, not pregnant, not infected by dengue previously and did not have cancer, autoimmune or haematological disorder. Median test was performed to compare the biomarker levels. A subgroup Mann-Whitney U test was analysed between severe dengue and non-severe dengue cases. Monte Carlo method was used to estimate the 2-tailed probability (P) value for independent variables with unequal number of patients. Results: All biomarkers except thrombomodulin has P value < 0.001 in differentiating among the healthy subjects, non-dengue fever, dengue without warning signs and dengue with warning signs/severe dengue. Subgroup analysis for all the biomarkers between severe dengue and non-severe dengue cases was not statistically significant except vascular endothelial growth factor-A (P < 0.05). Conclusions: Certain biomarkers were able to differentiate the clinical dengue cases. This could be potentially useful in classifying and determining the severity of dengue infected patients in the hospital.

Summary Aim The mortality of lung cancer remains high and methods for early diagnosis are still lacking. Recently, exhaled breath condensate (EBC) has been considered a potential tool for obtaining biological information leading to a reliable diagnosis of non-small cell lung cancer (NSCLC). Objective This study assessed the potentials of exhaled and serum concentrations of soluble(s) forms of intercellular adhesion molecule 1 (sICAM1), vascular cell adhesion molecule 1 (sVCAM1), and E-selectin as biomarkers for diagnosis and predicting metastasis in NSCLC patients. Methods We enrolled 33 patients with NSCLC, 35 patients with chronic obstructive pulmonary disease (COPD) and 30 healthy controls. EBC and serum samples from subjects were collected at the time of diagnosis and, where applicable, 3 months after surgical treatment. Measurements of sICAM1, sVCAM1, and sE-selectin were determined by enzyme immunoassay. Results Concentrations of sICAM1, sVCAM1, and sE-selectin in the EBC and sera of NSCLC patients were significantly elevated compared to COPD patients and healthy controls. The exhaled and serum levels of sICAM1 and sVCAM1, but not sE-selectin, decreased significantly after tumor resection from pre-surgery levels. In addition, analyzed results showed a correlation between exhaled sICAM1 levels and disease progression of NSCLC patients. Conclusions Our results suggest that the levels of sICAM1, sVCAM1, and sE-selectin in EBC and sera of NSCLC patients are higher than those of COPD patients or healthy controls. Moreover, exhaled sICAM1 may have prognostic value and potential as a biomarker for the diagnosis and prognosis of patients with lung cancer.

The main therapeutic strategy against human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) characterized by lower extremity motor dysfunction is immunomodulatory treatment, with drugs such as corticosteroid hormone and interferon-α, at present. However, there are many issues in long-term treatment with these drugs, such as insufficient effects and various side effects. We now urgently need to develop other therapeutic strategies. The heparinoid, pentosan polysulfate sodium (PPS), has been safely used in Europe for the past 50 years as a thrombosis prophylaxis and for the treatment of phlebitis. We conducted a clinical trial to test the effect of subcutaneous administration of PPS in 12 patients with HAM/TSP in an open-labeled design. There was a marked improvement in lower extremity motor function, based on reduced spasticity, such as a reduced time required for walking 10 m and descending a flight of stairs. There were no significant changes in HTLV-I proviral copy numbers in peripheral blood contrary to the inhibitory effect of PPS in vitro for intercellular spread of HTLV-I. However, serum soluble vascular cell adhesion molecule (sVCAM)-1 was significantly increased without significant changes of serum level of chemokines (CXCL10 and CCL2). There was a positive correlation between increased sVCAM-1and reduced time required for walking 10 m. PPS might induce neurological improvement by inhibition of chronic inflammation in the spinal cord, through blocking the adhesion cascade by increasing serum sVCAM-1, in addition to rheological improvement of the microcirculation. PPS has the potential to be a new therapeutic tool for HAM/TSP.

Soluble vascular cell adhesion molecule-1 (sVCAM-1) has a strong association with cardiovascular deaths in patients with coronary artery disease. The aim of this study is to explore the association between sVCAM-1 and cardiovascular mortality in maintenance hemodialysis (MHD) patients. Eighty-three clinically stable MHD patients (mean age of 59.4 ± 13.7 years) at a single hospital-based dialysis facility were included. sVCAM-1, soluble intercellular adhesion molecule-1 (sICAM-1), and soluble E-selectin (sE-selectin) were determined at study baseline. The study cohort was divided into higher and lower concentration groups by the median value. The all-cause and cardiovascular mortality of this cohort were followed for 7 years. The mean concentrations of sVCAM-1, sICAM-1, and sE-selectin were 1,393.08 ± 300.96, 230.16 ± 84.86, and 60.01 ± 42.00 ng/mL, respectively. The higher concentration groups of sVCAM-1 and sICAM-1 had higher all-cause mortality by Kaplan–Meier analysis (p = 0.002 and p = 0.030, respectively). Higher sVCAM-1 concentrations had a higher risk of all-cause and cardiovascular mortality (p = 0.006 p = 0.046, respectively) in Cox proportional hazards model analysis. In MHD patients, higher sVCAM-1 concentrations independently predict all-cause and cardiovascular mortality. This biomarker may be used as a valid surrogate marker for predicting outcomes.

Vascular cell adhesion molecule-1 (VCAM-1) is strongly upregulated in hearts of mice with coxsackie virus-induced as well as in patients with viral infection-triggered dilated cardiomyopathy. Nevertheless, the role of its soluble form as a biomarker in inflammatory heart diseases remains unclear. Therefore, we investigated whether plasma levels of soluble VCAM-1 (sVCAM-1) directly correlated with disease activity and progression of cardiac dysfunction in the mouse model of experimental autoimmune myocarditis (EAM). EAM was induced by immunization of BALB/c mice with heart-specific myosin-alpha heavy chain peptide together with complete Freund`s adjuvant. ELISA revealed strong expression of cardiac VCAM-1 (cVCAM-1) throughout the course of EAM in immunized mice compared to control animals. Furthermore, sVCAM-1 was elevated in the plasma of immunized compared to control mice at acute and chronic stages of the disease. sVCAM-1 did not correlate with the degree of acute cardiac inflammation analyzed by histology or cardiac cytokine expression investigated by ELISA. Nevertheless, heart to body weight ratio correlated significantly with sVCAM-1 at chronic stages of EAM. Cardiac systolic dysfunction studied with positron emission tomography indicated a weak relationship with sVCAM-1 at the chronic stage of the disease. Our data provide evidence that plasma levels of sVCAM-1 are elevated throughout all stages of the disease but showed no strong correlation with the severity of EAM.

Aim: Serum levels of soluble intracellular cell adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM) and monocyte chemotactic protein 1 (MCP-1), are elevated in patients with peripheral artery disease (PAD). However, the levels of these cell adhesion molecules in patients undergoing haemodialysis (HD) are unclear. Method: A total of 112 HD patients were included and PAD was diagnosed using the ankle-brachial index and Doppler ultrasound. Serum levels of sICAM-1, sVCAM-1 and MCP-1 were assayed using enzyme linked immunosorbent assay. Results: Out of 106 HD patients, 31 (27.7%) were diagnosed with PAD. After adjusting for risk factors, higher serum levels of sVCAM-1 and sICAM-1 were associated with PAD in HD patients, with an odds ratio of 5.3 (95% CI 3.3–65.5) and 2.7 (95% CI 1.2–21.8) respectively. Using sVCAM-1 and sICAM-1 for diagnosis of PAD in HD patients, sVCAM-1 had a sensitivity of 72.4% and specificity of 62.3% for sVCAM-1 and sICAM-1 had a sensitivity of 89.3% and a specificity of 40%. MCP-1 was not associated with PAD in HD patients. In addition, the fistula of HD patients with PAD had a lower A-V access flow. Conclusion: sVCAM-1 and sICAM-1 was associated with higher risk of PAD in HD patients. Moreover, HD patients with PAD had a lower blood flow and lower A-V access flow. Our results showed that sVCAM-1 and sICAM-1 may be used as screening markers for PAD in HD patients.

Inflammatory responses are an important element in the atherosclerotic process. Therefore, inflammatory markers can potentially serve as predictors of cardiovascular risk. However, the existing data are limited and controversial. We conducted a prospective cohort study with 263 patients with first acute ST-segment elevation myocardial infarction (STEMI) who were admitted to our Hospital within 6 h after the symptoms onset. Clinical data were recorded and serum admission levels of interleukin-6 (IL-6), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and soluble P-selectin (sP-selectin) were determined. The patients were then followed up for 3 years to document cardiovascular mortality. During the follow-up, 34 patients died from cardiovascular causes. The admission levels of IL-6 were significantly higher in these patients, whereas sICAM-1, sVCAM-1, and sP-selectin were comparable between these and the survived patients. The Kaplan-Meier plots revealed a significant increase in cardiovascular mortality with increasing levels of IL-6 (P = 0.0002, χ(2) test). The logistic regression analysis indicated that IL-6 was an independent predictor for cardiovascular mortality. To conclude, our findings indicate that elevated admission levels of IL-6, but not soluble adhesion molecules, provide valuable information for risk assessment of long-term cardiovascular mortality in patients with STEMI.

Background and aims MIAMI is a prospective multicenter clinical study designed to investigate the relationship between changes in carotid intima-media thickness (C-IMT) and changes in circulating markers of inflammation, thrombosis and endothelial activation in stable coronary patients treated for 20 ± 3.7 months with 20 mg/day atorvastatin. Methods and results Eighty-five subjects had their C-IMT, blood lipids and soluble markers measured at baseline, at the 12th month and at the end of the study. Almost all soluble markers decreased upon treatment except for high-sensitivity C-reactive protein (hs-CRP), interleukin-18 (IL-18), tissue factor pathway inhibitor-free (TFPI-free) and soluble vascular cell adhesion molecules-1 (sVCAM-1) which did not change significantly, and interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and soluble CD40 ligand (sCD40L) which increased. sCD40L, fibrinogen, tissue factor pathway inhibitor-total (TFPI-total), soluble intercellular adhesion molecules-1 (sICAM-1), sE-selectin, interleukin-8 (IL-8) and von Willebrand factor (vWF) changed significantly even after application of the Bonferroni correction for multiple comparisons. Changes in lipids did not correlate with C-IMT regression either when considered singly or when combined in a lipid score. Changes in soluble markers correlated poorly with C-IMT regression when analyzed singly, but strongly when combined in relevant composite scores (inflammation/coagulation score, endothelial activation score, soluble markers score and total score). Conclusion In patients with stable coronary artery disease treated with moderate doses of atorvastatin, carotid IMT regression correlated with changes of inflammation, thrombosis and endothelial activation profiles.

Background Cell adhesion molecules (CAMs) play a pivotal role in cutaneous localization of T cells. Tissue-selective localization of T lymphocytes to the skin is crucial for immune surveillance and in the pathogenesis of skin disorders. Objective To detect the profile of soluble CAMs in patients with cutaneous T-cell lymphoma (CTCL), we investigated the levels of intercellular adhesion molecule-1 (ICAM-1, soluble ICAM-1 [sICAM-1]); intercellular adhesion molecule-3 (sICAM-3); vascular cell adhesion molecule-1 (sVCAM-1); and E-selectin (sE-selectin) in sera from patients with T-cell–mediated skin diseases. Methods Serum levels of the 4 CAMs were measured by enzyme-linked immunosorbent assay in 42 participants including 11 patients with early stages of CTCL; 7 with advanced stages of CTCL including Sezary syndrome; 12 with inflammatory skin diseases (psoriasis and atopic dermatitis); 8 with skin diseases that may evolve into CTCL; and healthy individuals. Levels were correlated with biological parameters known as prognostic factors in non-Hodgkin lymphomas. Results In patients with CTCL, significantly increased levels of sICAM-1 and sICAM-3 were found when compared with healthy individuals and patients with inflammatory dermatosis. Soluble E-selectin and sVCAM-1 levels were not increased. There were significant positive correlations between sICAM-1 and sICAM-3 levels and each of them with β2-microglobulin levels. Limitations Limited number of patients was a limitation. Conclusion There is a distinct profile of soluble CAMs in patients with CTCL. However, future studies with a larger group of patients are needed to confirm these findings. We propose that high sICAM-1 and sICAM-3 levels have important implications in the context of immune response and immune surveillance in these patients.

PURPOSE: Vascular cell adhesion molecule 1 plays an important role in solid tumor enlargement and/or metastasis. This study evaluated the clinical significance of measuring serum levels of soluble vascular cell adhesion molecule 1 in colorectal cancer and aimed to clarify the biologic significance of its local expression. METHODS: Serum was collected from 161 patients with colorectal cancer and 26 healthy volunteers. Cancer tissue was collected from 128 patients. The level of soluble vascular cell adhesion molecule 1 in serum and cancer tissue was measured by enzyme-linked immunosorbent assay. RESULTS: The mean soluble vascular cell adhesion molecule 1 level in patients was significantly higher than that in control subjects. Elevated serum soluble vascular cell adhesion molecule 1 was significantly associated with clinicopathologic parameters such as tumor size, lymph node metastasis, distant metastasis, and poor prognosis. In Cox multivariate analysis, distant metastasis and elevated serum soluble vascular cell adhesion molecule 1 level were independent risk factors predicting poor prognosis. The prognosis for Stage 2 patients positive for soluble vascular cell adhesion molecule 1 was comparable to that for Stage 3 patients. In addition, the serum level of soluble vascular cell adhesion molecule 1 level was correlated negatively with the cancer tissue level. CONCLUSION: The preoperative level of soluble vascular cell adhesion molecule 1 level reflected disease progression and was a sensitive biomarker for colorectal cancer, especially Stage 2 disease.

Background: The aim of this study was to investigate the effect of maternal smoking during pregnancy on human milk interleukin-1β, tumor necrosis factor-α (TNF-α) and soluble vascular cell adhesion molecule-1 levels at the postpartum seventh day. Methods: Forty-four mothers (age range: 21–34 years) were enrolled in the study. Mothers were interviewed and classified according to their smoking status into one of two groups: the smoking mothers (n= 21) and the nonsmoking mothers (n= 23). Results: There were no significant differences between study groups with respect to human milk interleukin-1β (P= 0.12) and soluble vascular cell adhesion molecule-1 levels (P= 0.83). However, TNF-α levels were found to be significantly lower in the smoking mothers compared with the controls (P= 0.002). Conclusion: This study shows that maternal smoking during pregnancy affects the levels of TNF-α in milk. The protective effect of human milk against infections seems to be impaired in smoking mothers.

HYPOTHESIS: The aim of the present study was to evaluate the concentration of soluble intercellular adhesion molecule 1 and soluble vascular cell adhesion molecule 1 in patients affected by sudden sensorineural hearing loss (SSHL). STUDY DESIGN: Prospective study. SETTING: Tertiary referral center. PATIENTS: Patients affected by SSHL were evaluated. Inclusion criteria for this study were hearing loss of more than 30 dB hearing level affecting at least 3 contiguous frequencies, normal hearing on the contralateral ear, negative history of hearing loss or ear surgery in the affected ear, and magnetic resonance with gadolinium negative for VIII cranial nerve pathologic findings. INTERVENTION: Circulating levels of soluble intercellular adhesion molecule 1 and soluble vascular cell adhesion molecule (VCAM) 1 were evaluated by means of enzyme-linked immunosorbent assay. MAIN OUTCOME MEASURES: The levels of adhesion molecules in SSHL patients were compared with those of a control group. RESULTS: Intercellular adhesion molecule 1 and VCAM-1 levels in sera of patients with SSHL were significantly higher than those of the matched control subjects (p < 0.001). Statistical analysis did not show significant differences between the 2 groups in terms of the known vascular risk factors such as total and fractionated cholesterol, triglycerides, fibrinogen, erythrocyte sedimentation rate smoking, and diabetes. CONCLUSION: The results of this study show that in SSHL patients, there is an increased expression of circulating adhesion molecules confirming the existence of an endothelial dysfunction and supporting the vascular involvement in the pathogenesis of the disease. The identification of high levels of adhesion molecules and of the endothelial dysfunction open the way to selective pharmacologic treatments able to correct the activation of endothelial cells.

Type 2 diabetes mellitus is associated with elevated plasma triglyceride levels, low high-density lipoprotein cholesterol, and a high incidence of cardiovascular disease. Hydroxymethylglutaryl-coenzyme A reductase inhibitors and fibrates are frequently used in the treatment of diabetic dyslipidemia, but their specific impact on the inflammation processes involved in atherosclerosis remains to be fully characterized. The objective of this 2-group parallel study was to investigate the differential effects of a 6-week treatment with either atorvastatin 20 mg/d alone (n = 19) or micronized fenofibrate 200 mg/d alone (n = 19) on inflammation, cell adhesion, and oxidation markers in type 2 diabetes mellitus subjects with marked hypertriglyceridemia. In addition to the expected changes in lipid levels, atorvastatin decreased plasma levels of C-reactive protein (-26.9%, P = .004), soluble intercellular adhesion molecule 1 (-5.4%, P = .03), soluble vascular cell adhesion molecule 1 (-4.4%, P = .008), sE-selectin (-5.7%, P = .02), matrix metalloproteinase 9 (-39.6%, P = .04), secretory phospholipase A(2) (sPLA(2)) (-14.8%, P = .04), and oxidized low-density lipoprotein (-38.4%, P.0001). On the other hand, fenofibrate had no significant effect on C-reactive protein levels and was associated with reduced plasma levels of sE-selectin only (-6.0%, P = .04) and increased plasma levels of sPLA(2) (+22.5%, P = .004). These results suggest that atorvastatin was potent to reduce inflammation, oxidation, and monocyte adhesion in type 2 diabetes mellitus subjects with marked hypertriglyceridemia, whereas fenofibrate decreased sE-selectin levels only and was associated with an elevation of sPLA(2) levels.

Retinol-binding protein-4 (RBP-4) may increase insulin resistance (IR) in animals, with elevated levels reported in humans with obesity and type 2 diabetes. There are, however, few data on concentrations of RBP-4 in gestational diabetes mellitus (GDM).We measured fasting serum levels of RBP-4, soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) in 50 women at 28 weeks of gestation, divided according to the results of a 50 g glucose challenge test (GCT) and a 75 g oral glucose tolerance test (OGTT): (1) controls (n = 20), normal responses to both GCT and OGTT; (2) intermediate group (IG) (n = 15): false positive GCT, but normal OGTT; and (3) GDM group (n = 15), both GCT and OGTT abnormal. IR was assessed by homeostasis model assessment (HOMA-IR) and by insulin resistance index (IRI) based on glycemia and insulinemia during OGTT.All groups were matched for age and body mass index (BMI). RBP-4 levels (microg/ml, mean+/-standard deviation) were higher in women with GDM vs. controls (53.9 +/- 17.9 vs. 29.7 +/- 13.9, por = 0.001), with a trend towards higher RBP-4 in GDM compared with IG (38.0 +/- 19.3, p = 0.07). There was no significant correlation between RBP-4 and age, BMI, insulin, IRI or HOMA-IR, but there was a moderate, significant negative correlation between RBP-4 and sVCAM-1 (r(2) = 0.20, p = 0.001).RBP-4 levels are elevated in women with GDM, but do not correlate with IR indices and correlate negatively with sVCAM-1. The physiological significance of RBP-4 rise in women with GDM remains to be elucidated.

Background: Blood Soluble Vascular Cell Adhesion Molecule-1 (sVCAM-1) and Soluble Intercellular Adhesion Molecule-1 (sICAM-1) levels are increased in Mitral Stenosis (MS) patients, but whether this phenomenon is due to chronic rheumatic inflammation process or because of hemodynamic effect of mitral stenosis severity is not clear yet. Objective: This research aims to study the effect of mitral stenosis severity on blood sVCAM-1 and sICAM-1 levels. Method: This study is a cross sectional study. Research subjects were divided into 3 groups: control patients, pre BMV (Baloon Mitral Valvulotomy) group, and post BMV group (patients who have already undergone BMV for ? 1year). Blood sVCAM-1 and sICAM-1 were measured using quantitative sandwich immunoassay method in all groups, and echocardiographic study to evaluate MS severity (MVA (Mitral Valve Area), mMVG (mean Mitral Valve gradient), TVG (Tricuspid Valve Gradient), mPAP (mean Pulmonary Artery Pressure), and LAVI (Left Atrial Volume Index) were performed to pre BMV and post BMV group at the same day with the blood sample collections. Results: There were 23 normal subjects, 26 patients in pre BMV group, and 27 patients in post BMV group. The sVCAM-1 and sICAM-1 levels in patients with MS (pre BMV and post BMV group) were higher than normal control subjects (536,87 251,68 ng/ml vs 536,87 149,22 ng/ml; p0,05). Conclusion: There were no correlation between mitral stenosis severity with blood sVCAM-1 and sICAM-1 levels

Hemorrhagic fever with renal syndrome (HFRS) is an acute viral disease characterized by endothelial dysfunction. Vascular cell adhesion molecule (VCAM)-1 and intercellular adhesion molecule (ICAM)-2 provide costimulatory signals for the activation of T lymphocytes; these adhesion molecules play key roles in leukocyte adherence and propagation of inflammatory responses. They may be involved in the immunologic response that leads to vascular endothelial cell (VEC) and kidney damage of HFRS patients, and increased levels of soluble (s)VCAM-1 and sICAM-2 in plasma may indicate the severity of HFRS. We examined the presence of sVCAM-1 and sICAM-2 in 52 plasma samples collected from 52 patients. We tested these plasma samples for sVCAM-1 and sICAM-2 by double-antibody sandwich ELISA. We found variable, but persistently elevated, levels of sVCAM-1 and sICAM-2 throughout the various phases and types of the disease, which suggested sVCAM-1 may play an important role in the immunopathological lesions of HFRS and is closely correlated to the severity of HFRS and the degree of kidney damage. sICAM-2 may be associated with the hyperfunctioning of the cellular immune response.

Summary The aim of the present study was to explore the relationship between tissue levels of leptin, soluble interleukin-6 receptor (sIL-6R), high-sensitive-C-reactive protein (hs-CRP) and soluble vascular cell adhesion molecule-1 (sVCAM-1) in atherosclerotic plaques, and traditional risk factors. Coronary artery specimens were obtained from 35 consecutive patients (26 men and nine women) who underwent coronary artery bypass grafting procedure. The mean tissue levels of leptin, hs-CRP and sIL-6R were significantly higher in patients with diabetes mellitus than without diabetes mellitus. When patients were classified according to the smoking status, the mean tissue levels of leptin, hs-CRP and sIL-6R were significantly higher in current smokers than both former smokers and non-smokers. In addition, the mean tissue levels of leptin and sIL-6R were significantly higher in former smokers than non-smokers. There was a positive association between leptin and hs-CRP, sIL-6R and plasma glucose in all patients. Plasma HDL levels were associated negatively with atherosclerotic tissue levels of leptin. Tissue levels of sIL-6R were associated significantly in a positive manner with leptin, hs-CRP and plasma glucose, while tissue levels of hs-CRP were associated with both leptin and sIL-6R. In conclusion, it is attractive to speculate that hs-CRP, sIL-6R and leptin could act synergistically in course of local inflammatory activity and those molecules may not be just markers of inflammation and cardiovascular risk but are also likely to play a pathogenic role in atheromatous plaque. In addition, atherosclerotic tissue levels of CRP, sIL-6R and leptin were significantly higher in current smokers and patients with diabetes.

Purpose Angiogenesis is a critical process for cancer progression. We tested whether elevated circulating levels of the angiogenesis-related markers vascular endothelial growth factor (VEGF) and/or soluble vascular cell adhesion molecule-1 (sVCAM-1) are associated with prostate cancer diagnosis, stage, progression, and metastasis. Patients and Methods Plasma levels of VEGF and sVCAM-1 were measured on frozen, archival plasma obtained preoperatively from 215 consecutive patients who underwent radical prostatectomy for clinically localized disease, nine men with untreated prostate cancer metastatic to bones, and 40 healthy men without cancer. Results Plasma levels of both VEGF and sVCAM-1 were highest in patients with bone metastases (P < .001). VEGF levels were higher in patients with clinically localized disease than in healthy controls (P < .001). VEGF levels were elevated in patients with biopsy and final Gleason sum ≥ 7 (P = .036 and P = .020, respectively) and extraprostatic extension (P = .047). Higher preoperative VEGF was independently associated with metastases to lymph nodes (P < .001). Both VEGF and sVCAM-1 were independently associated with biochemical progression after adjustment for the effects of standard preoperative features (P = .014 and P = .039, respectively). VEGF remained independently associated with biochemical progression after adjustment for standard postoperative features (P = .019). Conclusion Plasma levels of VEGF increased incrementally from healthy controls to patients with clinically localized disease to patients with lymph node and skeletal metastases. Higher preoperative VEGF was independently associated with metastases to lymph nodes and biochemical progression after surgery in both pre- and postoperative models. Plasma sVCAM-1 was elevated in men with bone metastases and was associated with biochemical progression in a preoperative model.

Hyperhomocyst(e)inemia (HHcy) is a risk factor of endothelial dysfunction and preeclampsia. Soluble vascular cell adhesion molecule-1 (sVCAM-1), a specific marker of endothelial dysfunction, is elevated in preeclampsia. Few have assessed the joint contribution of these biomarkers in predicting preeclampsia. We assessed the extent to which HHcy and elevated sVCAM-1 are independently and jointly associated with preeclampsia. We conducted a case-control analysis of 100 preeclampsia cases and 100 controls to test our study hypothesis. Maternal plasma was collected before labor onset. Total plasma homocysteine (tHcy) was measured using high-performance liquid chromatography with electrochemical detection procedures. Plasma sVCAM-1 was determined using ELISA. Using the distribution of each analyte among controls, elevated tHcy was defined as plasma tHcy >6.6 µmol/l and elevated sVCAM-1 was defined as plasma concentrations >845 ng/ml (i.e., values above the median). Odds ratios (OR) and 95% confidence intervals (CIs) were calculated. Compared with women without elevated tHcy and without elevated sVCAM-1 (the referent group), those with elevated sVCAM-1 alone had a 4.1-fold increased risk of preeclampsia (95% CI 1.2–13.8). The OR for women with elevated tHcy alone was 2.2 (95% CI 0.6–7.9). The OR for women with elevated tHcy and sVCAM-1 was 13.2 (95% CI 4.1–42.2). Elevated tHcy and sVCAM-1 together were strongly associated with an increased risk of preeclampsia. Larger, prospective studies are needed to confirm these findings and to determine the extent to which elevated tHcy and sVCAM-1 together in early pregnancy are predictive of preeclampsia risk.

Background: Dysfunction of myocardium as a result of ischemia/reperfusion during coronary artery bypass grafting (CABG) is currently one of the biggest problems in cardiovascular surgery. In previous studies, it has been well established that activated leukocytes and coronary vascular endothelial cells play an important role in the development of cardiac tissue damage during ischemia followed by reperfusion. Interactions between both of these cell types require the expression of adhesion molecules on their surface. In certain conditions, on cell activation, the adhesion proteins may be released from activated cells in soluble form into circulation. The purpose of our study was to establish whether the use of blood cardioplegia modifies plasma levels of soluble intracellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble E-selectin (sE-selectin), and soluble L-selectin (sL-selectin) in comparison with crystalloid cardioplegia in patients undergoing CABG. Methods: Patients undergoing CABG were classified into two groups to receive cold crystalloid cardioplegia (St. Thomas’ Hospital) or cold blood cardioplegia (method of Buckberg), followed by a “warm-shot” of the solution. Coronary sinus and arterial blood samples were obtained from 50 patients (42 men and 8 women; age range, 34 to 73 years) before aortic cross-clamping, at the beginning of reperfusion, and after 30 min of reperfusion. Plasma levels of soluble adhesion molecules were measured using sensitive enzyme-linked immunosorbent assays. Results: The transcardiac release of sICAM-1 and sVCAM-1 following myocardial ischemia/reperfusion during CABG was evident in both groups of patients. However, the increase of soluble forms of both of these adhesion proteins was more significant in the group of patients receiving crystalloid cardioplegia. Crystalloid cardioplegia resulted in decreased plasma level of sE-selectin in the coronary sinus blood sample after 30 min of reperfusion. No significant changes in plasma levels of sL-selectin in either group were observed. Conclusion: Cardioplegia may affect the release of soluble forms of adhesion molecules from ischemic myocardium and modify endothelium activation in patients undergoing CABG.

The purpose of this study was to test whether transient increases in homocysteine would promote changes in markers of endothelial injury, cellular fibronectin (cFN), and soluble vascular cell adhesion molecule 1 (sVCAM-1). Homocysteine, cFN, and sVCAM-1 concentrations increased significantly in response to a methionine load by 6 hours in human subjects. However, no correlation was observed between homocysteine and cFN or sVCAM-1. To directly test whether homocysteine can injure endothelial cells, human umbilical vein endothelial cells (HUVEC) were incubated with increasing concentrations of homocysteine, plasma, or serum from hyperhomocysteinemic mice or from the methionine-loaded test subjects. cFN release was increased from endothelial cells cultured with plasma (but not serum) of hyperhomocysteinemic transgenic mice or from methionine-loaded human subjects. These data suggest that very high homocysteine concentrations can promote endothelial injury; however, this effect is likely mediated by secondary effects that include a factor(s) present in plasma that affects endothelial cells.

Acta Obstet Gynecol Scand 2002; 81: 713-719. © Acta Obstet Gynecol Scand 2002 Background. The purpose of this case-controlled study was to investigate whether plasma concentrations of TNF-receptors I and II and tumor necrosis factor-α-induced cell adhesion molecule 1 VCAM-1 could serve as more sensitive markers of tumor necrosis factor-α release in preeclamptic women than a direct measurement of circulating tumor necrosis factor-α. Methods. Plasma concentrations of soluble tumor necrosis factor receptor I and II, immunoreactive tumor necrosis factor-a and soluble cell adhesion molecule VCAM-1 were determined in 21 patients with severe proteinuric preeclampsia (23-35 weeks' gestation) and 21 gestational age-matched normotensive controls by enzyme-linked immunoassays. Concentrations of bioactive tumor necrosis factor-α were assessed by the WEHI 164 bioassay. Data were statistically evaluated by Wilcoxon's rank sum and sign tests, and Spearman's test was used to evaluate clinical and biochemical correlations...

Background: Knee osteoarthritis is the most common form of joint disorder and a leading cause of pain and functional disability among elderly female population. Type 2-diabetes is frequently reported comorbidity in elderly female patients with knee osteoarthritis. VCAM-1 is emerging as a strong and independent predictor for severe osteoarthritis. VCAM-1 is an inducible cell surface sialo glycoprotein and mediates heterotypic cellular aggregation. Therefore, the aim of this study is to assess the role of soluble vascular cell adhesion molecule-1 at the onset of knee osteoarthritis among type 2 diabetic postmenopausal women.Methods: The present study includes 100 type 2-diabetic female subjects of age above 50 years as cases and 100 normal healthy female age matched individuals as controls. Osteoarthritis of knee was ascertained using the American college of rheumatology classification criteria. Serum soluble VCAM-1 concentration was measured by ELISA method in all 200 subjects. Biochemical parameters-Fasting blood sugar and lipid profile were measured using Mind ray BS-400 and HbA1c was measured by turbidimetric immunoassay method. Statistical analysis was made by student independent sample t-test. Correlation was determined by using spearman’s rank correlation coefficient.Results: Serum level of soluble VCAM-1 was found statistically highly significant (p

OBJECTIVE Data from a small study testing imatinib to treat SSc were used to determine if cytokine changes were related to differences in clinical parameters to model future early phase trials pairing cytokine changes and clinical parameters. METHODS Plasma and punch skin biopsy specimens collected at baseline and 6 months were analysed for levels of 26 fibrotic and inflammatory cytokines using multiplexed immunoassays and ELISA. Seven of nine patients on active treatment had paired data. Biopsies were biopulverized and standardized to protein levels in the tissue homogenate. Plasma was frozen at -80°C and analysed using multiplexed immunoassays or ELISAs standardized to CRP. Correlations between fold changes in cytokines and differences in clinical parameters (skin score, physician and patient global assessments and HAQ) were performed. P < 0.01 was considered significant. RESULTS After 6 months of imatinib treatment, plasma levels of soluble vascular cell adhesion molecule 1 decreased significantly (P < 0.001), while tissue levels of soluble intercellular adhesion molecule 1 increased (P < 0.01). Some significant correlations between fold changes in certain plasma fibrotic and inflammatory cytokines and changes in clinical parameters after 6 months of treatment were found: patient global scores and IL-13 (r = 0.964, P < 0.0001); ESR and IL-12p70 (r = -0.903, P < 0.01); in tissue samples, patient global score and soluble E-selectin (r = 0.913, P < 0.01); and physician global score with sCD40L (r = -0.883, P < 0.01). CONCLUSION Some serum and tissue cytokines may have a role in early phase clinical trials of SSc, correlating with changes in clinical parameters. Serum and tissue samples could be analysed in early phase trials to determine whether they support the clinical observations. TRIAL REGISTRATION http://clinicaltrials.gov/show/NCT01545427.

OBJECTIVES: Maternal serum soluble vascular cell adhesion molecule-1 (sVCAM-1) and soluble intercellular adhesion molecule-1 (sICAM-1) were evaluated in preeclampsia to investigate whether these molecules could be helpful with regard to this pregnancy complication. STUDY DESIGN: The study population was composed of 30 preeclamptic patients with a mean gestational age of 35.5 ± 4.6 weeks and 20 age-matched and gestational age-matched normotensive uncomplicated pregnancies (controls). Blood samples from 7 of the 30 preeclamptic patients and 15 of the 20 controls in the second trimester were also analyzed. Data were analyzed by parametric methods. RESULTS: Significantly higher maternal serum sVCAM-1 levels were found in both groups of preeclamptic patients with and without fetal growth restriction (981 ± 145 ng/ml; n = 13; p < 0.0005 and 846 ± 84 ng/ml; p < 0.02, respectively) compared with controls (668 ± 186 ng/ml). In contrast, no significant difference was found in maternal serum sICAM-1 levels between preeclamptic and normotensive pregnancies, or in both adhesion molecules (1) in the controls between second and third trimester samples and (2) in the second trimester between pregnant women who developed preeclampsia later and gestational age-matched controls. CONCLUSION: These findings show a selective significant elevation of maternal serum sVCAM-1 in preeclampsia, with the highest values in cases complicated with fetal growth restriction, perhaps reflecting its angiogenic function. Hence, sVCAM-1 could be helpful in the diagnosis of this fetal complication in preeclampsia.

Objective Recent studies have shown that in vitro endothelial cells are activated by antiphospholipid antibodies and may support leukocyte adhesion. We studied levels of soluble intercellular adhesion molecule 1 (sICAM-1, sCD54), soluble vascular cell adhesion molecule 1 (sVCAM-1, sCD106), and soluble E-selectin (soluble endothelial leukocyte adhesion molecule 1 [sELAM-1, sCD62E]) in sera from patients with primary antiphospholipid syndrome (primary APS), and compared them with those from patients with systemic lupus erythematosus–associated APS (SLE-APS) or pure SLE, as well as with those from 2 control groups composed of healthy volunteers and patients with thrombosis unrelated to autoimmune diseases. Methods Serum samples from 24 patients with primary APS, 15 patients with SLE-APS, 22 patients with pure SLE, 48 control patients with thrombosis, and 18 healthy volunteers were examined using enzyme-linked immunosorbent assays specific for sICAM-1, sVCAM-1, and sELAM-1. Results Serum levels of sVCAM-1, but not sICAM-1 or sELAM-1, were significantly increased in all patient study groups compared with thrombosis control patients and healthy volunteers, but did not differ between the groups of patients with primary APS, SLE-APS, or pure SLE. Concentrations of sVCAM-1 were significantly higher in primary APS or SLE-APS patients with severe, recurrent thrombosis and were negatively correlated with platelet counts in primary APS patients. In patients with primary APS, sVCAM-1 levels were higher if there was thrombotic kidney involvement and correlated with creatinemia. Conclusion Serum sVCAM-1 concentrations are increased in patients with primary APS, especially those with repeated thrombotic events or kidney involvement. These findings suggest that endothelial/monocyte interaction may be important in the pathogenesis of primary APS.

Background: The serum levels of soluble forms of vascular cell adhesion molecule 1 (sVCAM-1) and E-selectin (sE-selectin) can be used as a marker of endothelial activation. Objective: We investigated whether the serum level of sVCAM-1 and sE-selectin in patients with localized scleroderma (LSc) was correlated with the clinical or serologic features of this disease. Methods: Serum samples from 59 patients with LSc, 20 patients with systemic sclerosis (SSc) and 29 healthy controls were examined using specific enzyme-linked immunosorbent assays. Results: The serum levels of sVCAM-1 and sE-selectin in patients with LSc were significantly higher than those of the healthy controls. The serum levels of sVCAM-1 and sE-selectin were correlated with both the number of sclerotic lesions and the number of involved areas. Conclusion: These results indicate that the serum levels of sVCAM-1 and sE-selectin may reflect the extent of the skin involvement (ie, the disease severity) and may be useful for monitoring the in vivo states of endothelial activation in LSc. (J Am Acad Dermatol 2000;42:64-9.)

Daniel Y, Kupferminc MJ, Baram A, Geva E, Fait G, Lessing JB. A selective increase in plasma soluble vascular cell adhesion molecule-1 levels in preeclampsia. AJRI 1999; 41:407-412 © Munksgaard, Copenhagen PROBLEM: The study was conducted to determine whether altered plasma levels of soluble intercellular adhesion molecule (ICAM)-1 and soluble vascular cell adhesion molecule (VCAM)-I are involved in the pathogenesis of preeclampsia. METHOD OF STUDY: Maternal plasma samples were collected from 20 patients with preeclampsia, 20 matched normotensive patients with uncomplicated pregnancies, and ten healthy nonpregnant women. Samples were assayed for soluble VCAM-I and soluble ICAM- by specific enzyme-linked immunosorbent assay. RESULTS: Both soluble VCAM-I and soluble ICAM-1 were detectable in the plasma of all preeclamptic, normotensive pregnant, and nonpregnant women. The mean plasma level of soluble VCAM-I was significantly higher in preeclamptic women compared to normotensive pregnant women (1831 ng/mL ± 534 ng/mL vs. 1254 ng/mL ± 386 ng/mL, respectively; P

Objective: To determine whether plasma and peritoneal fluid levels of soluble vascular cell adhesion molecule-1 (sVCAM-1) and soluble intercellular adhesion molecule-1 (sICAM-1) are altered in women with ovarian hyperstimulation syndrome (OHSS). Design: Prospective, case-control study. Setting: Lis Maternity Hospital and the Sara Racine IVF Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. Patient(s): The study group comprised 16 women with severe OHSS. The control groups comprised 10 women treated with controlled ovarian hyperstimulation and 8 women with normal findings at diagnostic laparoscopy. Intervention(s): Plasma samples were obtained from the study group and the first control group. Peritoneal fluid samples were obtained during paracentesis from the study group and during diagnostic laparoscopy from the second control group. Main Outcome Measure(s): Samples were assayed by specific ELISA for sVCAM-1 and sICAM-1. Result(s): The mean peritoneal fluid levels of sVCAM-1 and sICAM-1 and the mean plasma levels of sVCAM-1 were significantly higher in the women with OHSS than in the control groups. However, the mean plasma levels of sICAM-1 were comparable. A positive correlation was demonstrated between the levels of sVCAM-1 and plasma E 2 at the time of hCG administration and between the levels of sICAM-1 and number of ova retrieved. Conclusion(s): Our findings suggest that soluble cell adhesion molecules may have a role in the pathogenesis and progression of OHSS.

Angiotensin converting enzyme inhibitors (ACE-I) are a mainstay for the treatment of heart failure, and of diabetic microalbuminuria. Recently ACE-I have been found to decrease plasma levels of circulating vascular cell adhesion molecule-1 (cVCAM-1) in patients with congestive heart failure. As increased cVCAM-1 levels are pathognomonic for diabetics with microangiopathy, we investigated the effects of ACE-I on plasma levels of cVCAM-1, intercellular adhesion molecule (cICAM-1), and cE-selectin in microalbuminuric diabetics. In addition, the effects of ACE-I on plasma levels of plasminogen activator inhibitor (PAI-1) and of tissue plasminogen activator (TPA) were studied. Fosinopril (10 mg/day) was administered over 12 weeks to 11 microalbuminuric patients with non-insulin-dependent diabetes mellitus (NIDDM). As expected, baseline plasma concentrations of cE-selectin, cICAM-1, and cVCAM-1 were markedly higher in patients than in healthy control subjects (n = 82; P.001). PAI-1 levels in NIDDM were similar to those in control subjects, whereas TPA levels were about 25% lower in patients than in control subjects (P = .013). Serum levels of cVCAM-1 decreased by -19% (CI: -25% to -13%) after treatment with fosinopril (P = .003) and were no longer different from those of the control group. In contrast, plasma levels of cE-selectin, cICAM-1, PAI-1, and TPA were unaffected. As expected microalbuminuria decreased by -44% (CI: -65 to -22; P = .004). In conclusion, fosinopril lowered cVCAM-1 levels along with microalbuminuria in NIDDM. This may represent a novel mechanism of action of ACE-I in diabetes-associated endothelial dysfunction. Whether decreased VCAM-1 expression is responsible for the observed reduction in microalbuminuria, deserves further investigation.

The concentration of soluble vascular cell adhesion molecules (sVCAM-1) of serum and cerebrospinal fluid (CSF) was measured in clinically selected multiple sclerosis (MS) and systemic lupus erythematosus (SLE) patients, using an ELISA assay. The mean sVCAM-1 concentration in the serum of SLE patients was higher than normal. The mean CSF sVCAM-1 concentration was increased in the MS as in the SLE group. On analysis, the data suggests that there are some similarities in the immunological effects of these two different diseases of the central nervous system. A longitudinal analysis of the CSF is requested.

Adhesion molecules on the endothelial cell membrane play an important role in the pathogenesis of atherosclerosis. Levels of soluble forms of cell adhesion molecules are reportedly elevated in patients with peripheral artery vessel disease and in patients with an atherosclerotic aorta. The present study investigated the association of serum levels of soluble vascular cell adhesion molecule 1 (sVCAM-1), soluble intercellular adhesion molecule 1 (sICAM-1), and soluble P-selectin (sP-selectin) with coronary heart disease (CHD) and the extent of coronary atherosclerosis, and examined the influence of serum levels of lipids, lipoproteins and apolipoproteins (apo) in subjects with (n=52, M/F: 43/9) and without (controls, n=40, M/F:25/15) angiographically proven coronary atherosclerosis. After controlling for age and gender, levels of sVCAM-1 (least squares mean ± std error: 565±36 ng/ml vs 540±41 ng/ml, ns), sICAM-1 (261±17 ng/ml vs 247±19 ng/ml, ns), and sP-selectin (142 ±8 ng/ml vs 149±10 ng/ml, ns) in patients with coronary atherosclerosis were not different from those in controls, as assessed by an analysis of covariance. After also adjusting for body mass index, hypertension, diabetes mellitus, and smoking by a multiple logistic function analysis, the association of sVCAM-1, sICAM-1, and sP-selectin with CHD was still not significant. Levels of sVCAM-1, sICAM-1, and sP-selectin were also not related to the extent of coronary atherosclerosis as judged by the number of stenosed vessels. However, inverse (p

SummaryAn increasing number of descriptive reports on soluble adhesion molecules and association with various diseases are published. Throughout these reports soluble adhesion molecules are identified as markers of inflammation. Since atherosclerosis demonstrates features of a chronic inflammatory disease, a potential association of soluble adhesion molecules with atherosclerosis has been postulated. However, conflicting results have been reported. One reason for this might be the differing definitions of atherosclerosis and patient groups. Besides the definition of atherosclerosis based on clinical symptoms, few reports use a direct quantification of atherosclerosis in their search for a marker of atherosclerosis. In those reports that quantify atherosclerosis, sVCAM-1 seems to be more specific for atherosclerosis than other markers. The serum level of sVCAM-1 appears to correlate with the extent of atherosclerosis and might allow for the detection of early stages of atherosclerosis. Large scale prospective studies will have to prove that sVCAM-1 can be used as a diagnostic tool for the detection of early stages of asymptomatic atherosclerosis and whether an early therapeutic intervention based on this approach is able to prevent progression and manifestation of the clinical sequelae of atherosclerosis.

The present study is the first to report elevated serum levels of soluble (s)VCAM-1 in B-cell chronic lymphocytic leukaemia (B-CLL). A large cohort of 106 untreated patients was studied. sVCAM-1 was compared to known prognostic serum markers (soluble (s)ICAM-1; lactate dehydrogenase, LDH; sCD23; thymidine kinase, TK; beta2microglobulin, beta2m). The serum levels of sVCAM-1 reflected tumour burden as expressed by Binet/Rai stages more closely than any other marker. sVCAM-1 also reflected the kinetics of the disease as revealed by lymphocyte doubling time. sVCAM-1 was the only one of the studied markers which showed elevated levels in smouldering disease compared to controls. sVCAM-1, sICAM-1 and sCD23 (but not LDH, TK, beta2m) separated smouldering from non-smouldering B-CLL. Only sICAM-1, sCD23 and TK added independent prognostic information for survival to that of stage and lymphocyte doubling time. The expression of both adhesion molecules was examined in lymph node and splenic specimens. VCAM-1 and ICAM-1 were overexpressed by vascular endothelium and stroma, but the intensity of expression correlated poorly with serum levels of the soluble molecules. In conclusion, serum levels of sVCAM-1 correlated with tumour burden and other prognostic markers in B-CLL. VCAM-1 was overexpressed in tumour tissue as was ICAM-1. sVCAM-1 could prove a valuable marker in younger early-stage patients eligible for therapeutic trials.

Serum levels of soluble vascular cell adhesion molecule-1 (sVCAM-1. sCD106) were significantly elevated in patients with Hodgkin's disease (HD) (n = 101) compared to controls (n= 31) (P

In order to investigate whether brain endothelial cells activation and/or damage could be selectively monitorized, soluble vascular cell adhesion molecule 1 (sVCAM-1) and thrombomodulin (TM) levels were studied in serum and cerebrospinal fluid (CSF) of 39 multiple sclerosis (MS) patients in various phases of the disease, 19 patients with other non-inflammatory neurological diseases (OND) and 15 patients with inflammatory neurological diseases (IND). No differences in sVCAM-1 CSF levels were detected, except for lower levels in IND compared to OND. Serum TM levels were lower in IND compared to progressive MS patients. Moreover, a significant decrease both in VCAM index and in TM index was detected in IND compared to all other groups. TM index was higher in MS patients in progression as compared to OND. The combined analysis of sVCAM-1 and TM might be a useful tool in monitoring brain endothelium activation or damage in different phases of MS.

To investigate the metabolic and genetic associations of levels of soluble adhesion molecules, plasma levels of soluble E-selectin and vascular cell adhesion molecule-1 were measured in 60 non-insulin-dependent diabetes mellitus (NIDDM) patients, 60 first-degree relatives of NIDDM patients and 60 control subjects, none of whom displayed clinical features of vascular disease. In addition, E-selectin A561C genotype, coding for a serine to arginine change, was determined. E-selectin levels were elevated in the patient group; 57 [52-63] (mean [95% confidence intervals]) ng/ml, compared with both relatives; 44 [39-50] ng/ml p = 0.001 and controls 39.5 [36-43] ng/ml p = 0.0001. E-selectin levels correlated with triglycerides, tissue-plasminogen activator and plasminogen activator inhibitor-1 activity in all groups. Levels of E-selectin were related to E-selectin genotype, being higher in subjects possessing the arginine allele (51.4 vs 44.5 ng/ml p < 0.05). E-selectin levels were higher in males than females in controls (female 35 [32-39] vs male 45 [40-51] ng/ml p = 0.004), and NIDDM relatives (female 38 [33-44] vs male 52 [45-61] ng/ml p = 0.004) but not in NIDDM patients where levels were similar (female 58 [49-69] vs male 56 [50-62] ng/ml, ns). There was no difference in soluble vascular cell adhesion molecule-1 levels between the three groups (control 640 [598-686] ng/ml, NIDDM relatives 634 [593-678] ng/ml and NIDDM patients 664 [608-725] ng/ml). In controls and patients vascular cell adhesion molecule-1 levels correlated with von Willebrand factor (vWF). The results indicate that levels of E-selectin relate to vascular risk factors in control subjects, NIDDM relatives and NIDDM patients.

Twenty-three patients enrolled in th GUSTO-III study underwent serial measurements of soluble vascular cell adhesion molecule-1 (VCAM-1) and E-selectin by enzyme-linked immunosorbent assay at prespecified time intervals. Soluble VCAM-1, but not E-selectin levels, were increased in patients with acute myocardial infarction, indicating that VCAM-1 may serve as a marker of increased endothelial activation in acute myocardial infarction.