Levels of soluble VCAM-1, soluble ICAM-1, and soluble E-selectin during disease exacerbations in patients with systemic lupus erythematosus (SLE); a long term prospective study.

Active SLE is characterized by immune deposits and subsequent vascular inflammation in many organs. Expression and up-regulation of adhesion molecules is basic to migration of inflammatory cells into the tissues. Recently, soluble isoforms of these molecules have been described which might be an expression of their up-regulation in the tissues and, as such, of disease activity. The purpose of this study was to evaluate whether changes in levels of soluble adhesion molecules reflect disease activity. We analysed serial sera in a 6-month period preceding 22 consecutive exacerbations of SLE for levels of soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1 (sICAM-1), and sE-selectin. Levels were related to clinical disease activity (SLEDAI), and levels of anti-dsDNA and complement. At the time of maximal disease activity, levels of sVCAM-1 in patients with SLE were higher than those in controls (P < 0.0001), levels in patients with renal involvement being higher than in those without (P < 0.02). Levels of sVCAM-1 correlated with SLEDAI scores (P < 0.05) and, inversely, with levels of C3 (P = 0.01). In addition, in the presence of anti-dsDNA, levels of sVCAM-1 tended to correlate with levels of these autoantibodies (P < 0.1). Levels of sICAM-1 were normal and sE-selectin levels even decreased compared with controls. Levels of sVCAM-1 were higher at the moment of relapse (P = 0.001) than at 6 months before this time point. This rise correlated with the rise in SLEDAI score (P < 0.02). Levels of sICAM-1 and sE-selectin did not rise, and remained in the normal range in all exacerbations studied. In conclusion, in contrast to sICAM-1 and sE-selectin, levels of sVCAM-1 are increased, rise parallel to disease activity during exacerbations in SLE, and are associated with decreasing levels of complement factors. This favours the hypothesis of immune deposit formation, activation of the complement cascade and activation of endothelial cells. Concurrent up-regulation of vascular adhesion molecules may thus result in transmigration of activated inflammatory cells inducing tissue damage.     

Examination of soluble cell adhesion molecules in pregnancy induced hypertension]

This study was performed to determine whether or not the soluble-intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1) and endothelial leukocyte adhesion molecule-1 (sELAM-1) are sensitive markers of pregnancy induced hypertension (PIH). sICAM-1 concentrations were significantly higher (p < 0.05) in the mild PIH compared to non-pregnant women and normal pregnant groups. sVCAM-1 concentrations in the mild PIH group and the severe PIH group were significantly higher than the non-pregnant women group (p < 0.0001, p < 0.01, respectively) and the normal pregnant group (p < 0.0001, p < 0.0005, respectively). The concentrations of sELAM-1 in the mild PIH group were also significantly higher compared to normal pregnant group (p < 0.01). Our results suggest that soluble cell adhesion molecules may be useful markers detecting endothelial damage and dysfunction in patients with PIH.     

Indices of low-grade chronic inflammation in polycystic ovary syndrome and the beneficial effect of metformin

BACKGROUND: Women with polycystic ovary syndrome (PCOS) have an increased prevalence of insulin resistance (IR) and related disorders. Elevated serum levels of cellular adhesion molecules (CAMs) reflect low-grade chronic inflammation and have been associated with several insulin-resistant states. The objective of this study is to investigate whether soluble inflammatory markers [soluble intercellular adhesion molecule-1 (sICAM-1), soluble endothelial leukocyte adhesion molecule-1 (sE-selectin), soluble vascular cell adhesion molecule-1 (sVCAM-1) and C-reactive protein (CRP)] are altered in PCOS and to further elucidate the effect of metformin treatment on their levels. METHODS: Two young populations were studied [62 women with PCOS and 45 normal women of similar age, BMI and waist-to-hip ratio (WHR)]. Plasma levels of sICAM-1, sVCAM-1, sE-selectin and high-sensitivity CRP (hsCRP) were measured in both groups. Additionally, the effect of metformin on these molecules was investigated in 22 women with PCOS who accepted to metformin protocol (1700 mg daily for a 6-month period). RESULTS: In the total population studied, plasma levels of hsCRP (mg/l), sICAM-1 (ng/ml) and sE-selectin (ng/ml) were higher in the PCOS group compared with those in controls (hsCRP 1.31 +/- 0.22 versus 0.92 +/- 0.27, P = 0.014, sICAM-1 301.21 +/- 24.80 versus 209.86 +/- 17.05, P = 0.025, sE-selectin 57.37 +/- 4.08 versus 45.67 +/- 4.62, P = 0.045, respectively). sVCAM-1 (ng/ml) did not differ statistically among the two groups (P = 0.896). A significant reduction in hsCRP and sVCAM-1 was achieved after 6 months of metformin administration: PCOS pretreatment hsCRP 1.92 +/- 0.60 versus PCOS post-treatment hsCRP 0.52 +/- 0.26, P = 0.005; PCOS pretreatment sVCAM-1 668.09 +/- 98.38 versus PCOS post-treatment sVCAM-1 365.82 +/- 99.77, P = 0.039. CONCLUSION: These findings imply the presence of chronic inflammation in women with PCOS. Metformin decreases the levels of plasma inflammatory indices. Further investigation is required to determine whether these findings may prove to be of clinical significance for PCOS patients.     

Changes in circulating levels of soluble cell adhesion molecules following highly active antiretroviral treatment of HIV-1-infected patients

Increased levels of soluble cell adhesion molecules (sCAM) have been reported in HIV-1 infection and may possibly contribute to altering the adhesion mechanisms of phagocytic cells. We evaluated the effect of highly active antiretroviral therapy (HAART) on plasma levels of sL-selectin, sE-selectin, intercellular cell adhesion molecule-1 (sICAM-1), sICAM-3, and vascular cell adhesion molecule-1 (sVCAM-1). Study participants included 22 HIV-1-infected patients with a CD4+ T-cell count/microl below 500 who were started on a HAART regimen and followed up for 9 months. After the initiation of therapy, plasma sL-selectin concentrations progressively decreased to normal ranges in the majority of our patients (P < 0.001), while no changes in sE-selectin were found. In all patients sICAM-1 remained relatively constant at significantly elevated concentrations during the 9 months of therapy. A significant reduction in plasma concentrations of both sICAM-3 and sVCAM-1 was found; however, the levels of these sCAM were not normalized by HAART and remained significantly elevated throughout the study (P < 0.001). The reduced release of sL-selectin could improve the ability of phagocitic cells to migrate in response to chemotactic stimuli after starting HAART. On the other hand, the persistent elevation of sICAM-1, sICAM-3, and sVCAM-1 could reflect continuous HIV-1-mediated immune activation, despite adequate control of plasma HIV-1 replication by therapy.     

Soluble adhesion molecules in serum throughout the menstrual cycle

BACKGROUND: The female reproductive and immune systems are integrally linked with respect to shared cellular and molecular mediators. Cell adhesion molecules (CAMs) involved in leukocyte-endothelial interactions, e.g. intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin, are regulated by sex steroids when expressed by cultured endothelium, while uterine and ovarian CAM expression appears to be cyclically or gonadotrophin-regulated. METHODS AND RESULTS: To determine if these effects translate into changes in soluble CAMs (sICAM-1, sVCAM-1 and sE-selectin) levels in peripheral blood, normally cycling women received regular venous sampling throughout a complete menstrual cycle. Soluble ICAM-1 levels were maximal in the early and mid-follicular stages, progressively decreased throughout the remainder of the cycle and were significantly reduced in the late luteal stage (P < 0.001). Levels of sVCAM-1 fluctuated during the follicular phase and mid-cycle, but also declined in the late luteal phase (P < 0.01), whereas sE-selectin concentration did not vary markedly across the menstrual cycle. Plasma hormone and urinary hormone metabolite levels confirmed precise cycle tracking and revealed an inverse relationship between sICAM-1 and estradiol (r = -0.38, P < 0.005). A negative correlation was also apparent between sVCAM-1 and circulating monocyte cell numbers (r = -0.47, P < 0.001). CONCLUSIONS: The normal cyclic variation in peripheral sICAM-1 and sVCAM-1 levels reported here may reflect uterine and/or ovarian tissue remodelling events, and is of particular importance if soluble CAM levels are utilized as biological markers of certain disease states in women of reproductive age.     

Increased plasma concentrations of sICAM-1, sVCAM-1 and sELAM-1 in patients with Plasmodium falciparum or P. vivax malaria and association with disease severity.

Increased serum concentrations of soluble intercellular adhesion molecule-1 (sICAM-1), soluble endothelial leucocyte adhesion molecule-1 (sELAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) were detected in Danish malaria patients infected with sequestering Plasmodium falciparum or non-sequestering P. vivax parasites, as well as in patients with sepsis or meningitis. Levels of soluble adhesion molecules remained elevated in the P. falciparum patients for several weeks after initiation of treatment. Plasma concentrations of sICAM-1, sVCAM-1 and sELAM-1 were higher in Gambian children with severe P. falciparum malaria than in children with mild malaria. Plasma levels of sVCAM-1 and sELAM-1 were significantly correlated. Plasma levels of sELAM-1 and sVCAM-1 may reflect endothelial inflammatory reactions and these reactions may be harmful for humans infected with malaria parasites.     

Levels of intracellular adhesion molecule-1 and vascular cell adhesion molecule-1 in children with Henoch-Sch?nlein purpura.

BACKGROUND AND PURPOSE: Henoch-Sch?nlein purpura (HSP) is a small vessel vasculitis. Soluble adhesion molecules play a very important role in the immuno-inflammatory reaction of damaged vascular tissues. This study investigated the prognostic and diagnostic potential of soluble intracellular adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (sVCAM-1) in HSP. METHODS: Serum levels of sICAM-1 and sVCAM-1 were studied in 26 children with HSP. Paired blood samples (during acute and convalescent stages) were collected from 17 of the children and assayed by enzyme-linked immunosorbent assay. Correlations with clinical manifestations were examined. Seventeen healthy children served as controls. RESULTS: Both sICAM-1 and sVCAM-1 were significantly elevated at the acute stage compared with the remission stage of HSP patients versus controls (p=0.006 and p=0.0173, respectively). CONCLUSIONS: Although the levels of sICAM-1 and sVCAM-1 were not correlated with the severity of clinical manifestations in HSP, these soluble adhesion molecules may serve as diagnostic markers.     

Differential up-regulation of circulating soluble selectins and endothelial adhesion molecules in Sicilian patients with Boutonneuse fever.

In 150 patients with Boutonneuse fever (BF), caused by Rickettsia conorii, we studied the plasma levels of soluble L-selectin (sL-selectin), vascular cell adhesion molecule-1 (sVCAM-1), intercellular adhesion molecule-1 (sICAM-1) and E-selectin (sE-selectin) in various phases of disease to clarify their role in disease evolution. Results indicate that during the acute phase of BF there is a significant increase in the serum levels of sL-selectin, sE-selectin, sVCAM-1 and sICAM-1. sL-selectin and sVCAM-1 returned to normal levels in the third week of disease, whereas sE-selectin and sICAM-1 persisted at significantly high levels even after the third week. The secretion of these soluble CAMs in BF is mainly the result of leucocyte expression and endothelial cell activation, but secretion also appears to mediate anti-inflammatory activities, moderating leucocyte adhesion and reducing in particular lymphocyte and monocyte infiltration. Only sL-selectin serum levels were found to correlate with the acute phase of infection characterized by fever.     

Soluble endothelium-associated adhesion molecules in patients with Graves' disease.

The targeting and recruitment of inflammatory cells to vascular endothelium in Graves' disease (GD) is mediated by intercellular adhesion molecule-1 (ICAM-1), endothelial leucocyte adhesion molecule-1 (ELAM-1), and vascular cell adhesion molecule-1 (VCAM-1). We have studied serum levels of soluble ICAM-1 (sICAM-1), soluble ELAM-1 (sELAM-1), and soluble VCAM-1 (sVCAM-1) in patients with GD (n = 21) and in patients with iodine-deficient goitre (IDG) (n = 23). The serum levels of sICAM-1 were markedly elevated in patients with GD before treatment with thiamazole (median 560 ng/ml versus 185 ng/ml in patients with IDG). In addition, elevated serum concentrations of sELAM-1 (median 85 ng/ml versus 33 ng/ml, respectively) and sVCAM-1 (median 42 ng/ml versus 15 ng/ml, respectively) were observed in patients with GD (P < 0.01 for all). The serum levels of sELAM-1 and sVCAM-1 dropped significantly after initiation of therapy and were within the normal range after 4, and 8 weeks of therapy, respectively. Serum levels of sICAM-1 were elevated even after 8 weeks of therapy. Serum levels of sVACM-1 and sICAM-1 correlated with the serum concentrations of anti-thyroid-stimulating hormone (TSH)-receptor antibodies (TSHR-R) (n = 21; r = 0.929 and r = 0.810, respectively) and anti-thyroid peroxidase antibodies (TPO-Ab) (n = 21; r = 0.673 and r = 0.750, respectively). However, no correlation between sELAM-1 and TPO-Ab, TSHR-R, and anti-thyroglobulin antibodies (Tg-Ab), respectively, could be found. In addition to thyroid hormones and autoantibodies, serum concentrations of sELAM-1 and sVCAM-1, but not sICAM-1, could be useful as clinical markers for disease activity.     

急性心肌梗塞病人细胞粘附分子与补体激活成分的动态变化

目的:探讨急性心肌梗塞(AMI)病人血浆细胞粘附分子和补体活化成分的变化。方法:采用酶联免疫吸附法(ELISA),检测了67例AMI病人发病第1、4、7d时和38例健康人,42例陈旧性心肌梗塞(OMI)病人白细胞CD18表达、血浆可溶性细胞间粘附分子-1(sICAM-1)、可溶性血管细胞间粘附分子-1(sVCAM-1)和血浆补体活化片段(sC5b-9)浓度的变化。结果:AMI病人白细胞CD18表达、sICAM-1、sVCAM-1和sC5b-9浓度非常显著高于对照组和OMI病人(P＜0.01)。发病第1-7d,白细胞CD18表达、sICAM-1、sVCAM-1和sC5b-9浓度逐渐降低。死亡者和伴有室性心律失常者各指标增高较存活者和无室性心律失常者更明显(P＜0.01)。AMI病人白细胞CD18表达、sICAM-1、sVCAM-1浓度与sC5b-9浓度呈正相关(r=0.648,0.652,0.668,0.698,0.914,0.725,0.737,0.752,0.792,P＜0.01),白细胞CD18表达与sICAM-1、sVCAM-1浓度呈正相关(r=0.662,0.683,0.695,0.738,0.744,0.745,P＜0.01)。结论:细胞粘附分子和补体激活成分的相互作用参与了AMI的发生和发展,且与病情严重程度和预后有密切关系。     

Soluble cell adhesion molecules and von Willebrand factor in children with Kawasaki disease.

Fifty-nine children with acute Kawasaki disease (KD), a childhood vasculitis, were compared with 35 children with fever due to infection and 48 healthy children. Levels of soluble E-selectin (sE-selectin), soluble intercellular adhesion molecule-1 (sICAM-1), and soluble vascular cell adhesion molecule-1 (sVCAM-1) in the healthy children were double those found in adults. All three soluble cell adhesion molecules and von Willebrand factor (vWF) were higher in the children with KD than in the healthy children, but only sE-selectin, a marker for activated endothelial cells, and sICAM-1 were higher than in the febrile children. The high levels of vWF in KD appear to reflect the prominent acute-phase reaction. This information can help us to understand further the complex interactions between cytokines, circulating inflammatory cells and the vascular endothelium, and may lead to new therapeutic avenues in KD and other inflammatory diseases and vasculitides.     

Vascular inflammation in cerebral small vessel disease

Cerebral small vessel disease (CSVD) is considered to be caused by an increased permeability of the blood-brain barrier and results in enlargement of Virchow Robin spaces (VRs), white matter lesions, brain microbleeds, and lacunar infarcts. The increased permeability of the blood-brain barrier may relate to endothelial cell activation and activated monocytes/macrophages. Therefore, we hypothesized that plasma markers of endothelial activation (adhesion molecules) and monocyte/macrophage activation (neopterin) relate to CSVD manifestations. In 163 first-ever lacunar stroke patients and 183 essential hypertensive patients, we assessed CSVD manifestations on brain magnetic resonance imaging (MRI) and levels of C-reactive protein (CRP), neopterin, as well as circulating soluble adhesion molecules (sICAM-1, sVCAM-1, sE-selectin, sP-selectin). Neopterin, sICAM-1 and sVCAM-1 levels were higher in patients with extensive CSVD manifestations than in those without (p < 0.01). Neopterin levels independently related to higher numbers of enlarged Virchow Robin spaces (p < 0.001). An inflammatory process with activated monocytes/macrophages may play a role in the increased permeability of the blood brain barrier in patients with CSVD.     

Elevation of serum soluble vascular cell adhesion molecule-1 (sVCAM-1) levels in bronchial asthma.

We have previously shown the elevation of serum soluble intercellular adhesion molecule-1 (sICAM-1) and soluble E-selectin (sE-selectin) in patients with bronchial asthma during asthma attacks. In the present study, we extended our earlier study by measuring serum sVCAM-1 levels by ELISA in 45 patients with bronchial asthma (23 atopic and 22 non-atopic) during asthma attacks and in stable conditions in order to assess further the state of adhesion molecules in allergic inflammation of bronchial asthma. The levels of sVCAM-1 in sera obtained during bronchial asthma attacks were higher than those in sera obtained in stable conditions. These findings were observed regardless of atopic status. To examine the regulatory mechanism in the elevation of serum sVCAM-1 levels, serum tumor necrosis factor-alpha (TNF-alpha) levels were measured by ELISA. TNF-alpha levels in sera obtained during bronchial asthma attacks were higher than those in sera obtained in stable conditions. The nature of change in serum TNF-alpha levels correlated with the nature of change in serum sVCAM-1 levels, but serum TNF-alpha levels did not correlate with serum sVCAM-1 levels. These results suggest that higher levels of sVCAM-1 during asthma attacks may reflect the up-regulation of VCAM-1 expression in allergic inflammation, and that a soluble form of VCAM-1 molecules may be useful markers for the presence of allergic inflammation. TNF-alpha is shown to enhance the expression and release of VCAM-1 in vitro, however; the regulatory mechanism in the elevation of serum sVCAM-1 levels remains to be clarified.     

Serum soluble adhesion molecules (sICAM-1, sVCAM-1 and sE-selectin) in healthy school aged children and adults

The aim of this study was to map normal levels of serum soluble isoforms of adhesion molecules in relation to age and sex in the group of school-aged children. sICAM-1, sVCAM-1 and sE-selectin were determined in the group of 158 normal children subdivided into two subgroups; 6-10 years (68 children, median age 8 years) and 11-15 years (90 children, median age 12 years) and in 70 normal adult blood donors (25 females and 45 males, median age 46 years). The levels of sICAM-1 and sE-selectin fell down significantly over the age range 6-15 years, while the level of sVCAM-1 was remained. Age-related normal ranges were established using correlation analysis and were expressed as the 5%-95% percentiles intervals: sICAM-1 206.8-486.8 ng/ml, sE-selectin 36.7-153.2 ng/ml in the group of 6-10 years old children, sICAM-1 184.1-354.0 ng/ml, sE-selectin 29.9-114.1 ng/ml in group of 11-15 years old children. The levels of sVCAM-1 were 359.6-822.0 ng/ml and were constant within the examined age interval from 6 to 15 years. The influence of sex was also assayed and it was not statistically significant in any age category tested. Normal ranges of sICAM-1 (60.2-218.4 ng/ml), sE-selectin (8.3-116.9 ng/ml) and sVCAM-1 (338.0-1148.0 ng/ml) were established for adult population of healthy blood donors using the same methods.     

Normal levels of soluble E-selectin, soluble intercellular adhesion molecule-1 (sICAM-1), and soluble vascular cell adhesion molecule-1 (sVCAM-1) decrease with age

sE-selectin, sICAM-1, sVCAM-1 and von Willebrand factor (vWF) were assayed in 238 samples in a longitudinal study of 81 normal children from 9.5 to 15.5 years old. Multilevel modelling was used to quantify changes with age. sE-selectin, sICAM-1 and sVCAM-1 all fell significantly over the age range (by 17%, 16%, and 10%, respectively). In contrast, levels of vWF were not age-dependent. Our findings highlight the need for age-matched controls when studying cell surface adhesion molecules in disease groups, and may imply developmental changes in expression of these molecules and their shedding from the cell surface.     

The relationship of soluble ICAM-1, VCAM-1, P-selectin and E-selectin to cardiovascular disease risk factors in healthy men and women.

BACKGROUND: Clinical studies have shown that elevated serum concentrations of cell adhesion molecules such as inter-cellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1), E-selectin (ESEL) and P-selectin (PSEL) may be independent risk factors for atherosclerosis and cardiovascular disease (CVD). Less is known of the relationship of these inflammatory markers with established CVD risk factors in healthy individuals, particularly women. OBJECTIVE: The aim of this study was to examine cross-sectional relationships between the concentrations of soluble adhesion molecules (sICAM-1, sVCAM-1, sPSEL and sESEL) and smoking behaviour, body composition, blood pressure, serum lipids and physical activity in a large sample of healthy men and women, with special emphasis on interactions between smoking and other CVD risk factors. SUBJECTS: The analysis included 592 healthy white adults aged 18-82 years. RESULTS: There were no sex differences in the concentrations of sICAM-1, sVCAM-1 and sPSEL, but men had higher sESEL levels than women (p < 0.0001). Male and female smokers had higher sICAM-1 and sESEL levels than non-smokers and soluble cell adhesion molecules (CAMs) were correlated with the pack-years of cigarette smoking (r = 0.3-0.4, p < 0.0001, significant in women only). Significant independent associations were found between soluble CAMs and smoking, waist-hip ratio (WHR), blood pressure, high density lipoprotein cholesterol and total cholesterol. Furthermore, significant interaction effects were found in women, such that the relationship between CAMs and lipid concentrations and WHR were stronger in smokers than non-smokers. In conclusion, the concentration of soluble CAMs, particularly sICAM-1 and sESEL, reflect the level of established CVD risk factors in apparently healthy men and women, adding to the evidence that these factors contribute to CVD through their inflammatory effects on the vascular endothelium.     

Do Soluble Cell Adhesion Molecules Play a Role in Endometriosis?

PROBLEM: Endometriosis is a chronic inflammatory disease associated with diverse immunologic disturbances. Cell adhesion molecules are essential for the development of immune and inflammatory reactions. This study was conducted to investigate whether or not serum and peritoneal levels of soluble cell adhesion molecules are altered in women with endometriosis. METHOD OF STUDY: The study group comprised five women with moderate-to-severe endometriosis. Eight healthy women with a normal diagnostic laparoscopy served as controls. Serum and peritoneal fluid samples from both groups were analyzed for the soluble isoform of intercellular cell adhesion molecule-1 (sICAM-1). vascular cell adhesion molecule-1 (sVCAM-1), endothelial selectin (sES), and platelet selectin (sPS). RESULTS: Serum levels of sICAM-1 were significantly increased in women with endometriosis (median levels: 410.4 ng/mL; range: 233.9 ng/mL 598.4 ng/mL vs. 235.7 ng/mL; range: 187.4 ng/mL -323.7 ng/mL; P = 0.02). Although the levels of sVCAM-1, sES, and sPS in both samples were higher in the study group, the differences did not reach significance. CONCLUSIONS: Our results suggest a role of ICAM-1 in the pathophysiology of endometriosis. However. the role of other investigated cell adhesion molecules should be confirmed by further studies.     

Blood serum levels of vascular cell adhesion molecule (sVCAM-1), intercellular adhesion molecule (sICAM-1) and endothelial leucocyte adhesion molecule-1 (ELAM-1) in diabetic retinopathy

BACKGROUND: Interaction between cells via intimate cell-cell contact is facilitated by a cell surface molecules, termed adhesion molecules. The aim of the study was to evaluate the blood serum concentration of soluble forms of vascular cell adhesion molecule (VCAM-1), intercellular adhesion molecule (ICAM-1) and endothelial leukocyte adhesion molecule-1 (ELAM-1) in patients with type 1 diabetes mellitus without and with diabetic retinopathy. MATERIALS AND METHODS: The study was performed in 75 patients with type 1 diabetes mellitus, 35 without retinopathy (group 1) and 40 with retinopathy (group 2). Soluble forms of VCAM-1, ICAM-1 and ELAM-1 were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: The serum concentration of sICAM-1 and sELAM-1 were significantly elevated and the concentration sVCAM-1 was elevated but not significantly in diabetic patients when compared with control subjects. There was a significant difference in VCAM-1 concentrations between the control group and group 2 (965.9 +/- 229.0 vs. 1283.7 +/- 387.6 ng/ml, p < 0.05) and between group 1 and group 2 (1115.0 +/- 285.5 vs. 1283.7 +/- 387.6 ng/ml, p < 0.05). There were significant differences in sICAM-1 concentrations between the control group and group 1 (p < 0.05) and between the control group and group 2 (p < 0.05). Where was no significant difference in sICAM-1 concentration between group 1 and 2 (405.2 +/- 135.9 vs. 443.1 +/- 112.7 ng/ml, p = 0.08). ELAM-1 concentration was significantly elevated in group 2 (120.5 +/- 49.3 ng/ml) when compared with the control group (51.7 +/- 18.1 ng/ml, p < 0.005) and with group 1 (81.2 +/- 27.7 ng/ml, p < 0.05). CONCLUSIONS: The correlations found between sVCAM-1, sICAM-1 and sELAM-1 and the presence of retinopathy suggest that cellular adhesion and neovascularization may be linked processes.     

Differential dose-dependent effects of prednisolone on shedding of endothelial adhesion molecules during human endotoxemia

Low dose prednisolone was shown to be beneficial in the treatment of the Acute respiratory distress syndrome (ARDS) and septic shock. One corticosteroid-induced effect, postulated to mediate corticosteroid-induced anti-inflammatory effects, is decreased expression of adhesion molecules on endothelial cells, thereby preventing leukocyte recruitment at inflammatory sites. The current study aimed to investigate the effect of increasing doses of prednisolone on the release of soluble adhesion molecules in healthy volunteers challenged with endotoxin. Therefore, 32 healthy, male volunteers received prednisolone orally at doses of 0mg, 3mg, 10mg or 30 mg at 2h before injection of endotoxin prepared from Escherichia coli (4 ng/kg) and levels of soluble E-selectin (sE-selectin), soluble VCAM-1 (sVCAM-1) and soluble ICAM-1 (sICAM-1) were measured. Levels of all markers were increased after induction of endotoxemia. Levels of sE-selectin were inhibited by a dose of 3mg prednisolone and levels of sVCAM-1 were decreased after a dose of 10mg. Maximal inhibition of both sE-selectin and sVCAM-1 levels was achieved by the highest dose of prednisolone 30 mg. Remarkably, prednisolone 3mg potentiated endotoxin-induced sVCAM-1 release. Levels of sICAM-1 were not affected by prednisolone. Together, the data suggest that prednisolone differentially and dose-dependently influences the release of soluble endothelial adhesion molecules during human endotoxemia.     

三种血管内皮损伤指标血清水平与冠心病病变范围的关系

目的:探讨血清可溶性血管细胞黏附分子-1(sVCAM-1)、可溶性细胞间黏附分子-1(sICAM-1)、血管性血友病因子(vWF)水平与冠心病(CHD)病变范围的相关性。方法:根据冠脉造影结果将87例患者分为CHD组(63例)和对照组(24例)。采用ELISA平行检测两组血清sVCAM-1、sICAM-1和vWF水平,酶法测定血脂水平,比较两组患者sVCAM-1、sICAM-1、vWF及血脂水平的差异,并进行相关性分析;以冠脉狭窄支数作为判断CHD病变范围的依据,探讨不同病变范围患者血清sVCAM-1、sICAM-1和vWF的水平变化。结果:CHD组血清sVCAM-1、sI-CAM-1、vWF水平显著高于对照组(P<0.01);血清sVCAM-1、sICAM-1和vWF水平与血脂水平之间无明显相关性(P>0.05);单支冠脉狭窄组血清sVCAM-1、sICAM-1水平显著低于多支冠脉狭窄组(P<0.05)。结论:CHD患者血清sV-CAM-1、sICAM-1和vWF水平升高,sVCAM-1、sICAM-1水平与CHD病变范围有关。