Soluble L-selectin level is a marker for coronary artery disease in type 2 diabetic patients

OBJECTIVE: To investigate whether the fall in soluble L-selectin (sL-selectin) level constitutes a marker for myocardial ischemia. RESEARCH DESIGN AND METHODS: The levels of soluble forms of adhesion molecules, i.e., intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), E-selectin (sE-selectin), P-selectin (sP-selectin), and L-selectin (sL-selectin), were compared in type 2 diabetic patients without inflammatory syndrome but with symptomatic coronary artery disease (CAD) (group 1, n = 11), with silent ischemic disorders and proven coronary stenoses (group 2, n = 11), with silent myocardial ischemia (SMI) and normal coronary angiography (group 3, n = 10), and without proven SMI (group 4, n = 13). These levels were compared with those of 22 control subjects. RESULTS: The sL-selectin level was significantly lower in groups 1, 2, or 3 with symptomatic CAD or with SMI as compared with the control group (P = 0.0004). Group 4 without myocardial ischemia did not significantly differ from the control subjects (P = 0.6). In type 2 diabetic patients, after controlling for HbA1c, a partial correlation between sL-selectin and the CAD status was significant (P = 0.001). sICAM-1 and sP- or sE-selectin did not differ significantly between type 2 diabetic patients and control subjects or among the different groups of patients. The sVCAM-1 level in type 2 diabetic patients was significantly higher than in the control subjects (P = 0.001), but there were no significant intergroup differences (P = 0.4). CONCLUSIONS: In type 2 diabetic patients, sVCAM-1 is increased with regard to glycemic control, whatever the CAD status. In type 2 diabetic patients with symptomatic CAD or SMI associated with coronary stenoses, sL-selectin is significantly decreased. A marked fall in sL-selectin might constitute a marker for silent CAD in type 2 diabetic patients.     

Circulating endothelial adhesion molecules (sE-selectin, sVCAM-1 and sICAM-1) during rHuG-CSF-stimulated stem cell mobilization

The role of leukocyte-endothelial cell interactions during granulocyte colony-stimulating factor (G-CSF)-induced stem cell mobilization is unclear. To examine endothelial activation during this process, we determined levels of circulating endothelial adhesion molecules in healthy donors undergoing G-CSF-mobilized stem cell collection. Plasma levels of soluble (s) E-selectin, soluble intercellular adhesion molecule-1 (sICAM-1), and soluble vascular cell adhesion molecule-1 (sVCAM-1) were serially determined by enzyme-linked immunosorbent assays in 10 healthy donors during G-CSF-stimulated stem cell mobilization. There was a significant increase in plasma levels of all three endothelial adhesion molecules (sE-selectin, p = 0.01; sICAM-1, p = 0.003; sVCAM-1, p = 0.0002) between day 1 and day 5 of G-CSF stimulation, but only sVCAM-1 concentrations exceeded the range obtained from unstimulated controls in all stem cell donors. Increases of sCAM were accompanied by increased numbers of white blood cells and CD34(+) progenitors in peripheral blood. G-CSF-stimulated peripheral blood progenitor cells (PBPC) mobilization results in increased levels of circulating endothelial adhesion molecules that were most evident for VCAM-1 molecules. Because soluble VCAM-1 remains active in binding to the VLA-4 receptor on CD34(+) cells, it may reduce stem cell adhesiveness to endothelial cells and to bone marrow microenvironment.     

Effect of narrow-band UVB phototherapy on soluble cell adhesion molecules in patients with psoriasis vulgaris

This study investigated the effect of narrow-band ultraviolet B (NB-UVB) phototherapy on serum levels of the soluble cell adhesion molecules sE-selectin, sP-selectin, sL-selectin and soluble intercellular adhesion molecule-1 (sICAM-1) in 58 patients with psoriasis vulgaris. Psoriasis Area and Severity Index (PASI) scores significantly decreased after treatment, confirming the efficacy of NB-UVB phototherapy. Serum levels of sE-selectin also decreased significantly after treatment, and levels of sICAM-1 showed a significant correlation with PASI score and with levels of sE-selectin. The efficacy of NB-UVB phototherapy in improving psoriatic lesions may be a function of decreased serum levels of E-selectin. These findings emphasize the complex roles of soluble cell adhesion molecules in the immunopathogenesis of psoriasis.     

Comparison of soluble ICAM-1, VCAM-1 and E-selectin levels in patients with episodic cluster headache and giant cell arteritis

The pathophysiology of cluster headache (CH) is supposed to involve the lower posterior part of the hypothalamus, the trigeminal nerve, autonomic nerves and vessels in the orbital/retro-orbital region. The exact connection of this hypothalamic–trigemino–autonomic–vascular axis is not fully understood. The presence of inflammation in the perivascular tissue of the retro-orbital region has been presented as a possible mechanism behind the pain and the sympatheticoplegia sometimes observed during headache attacks. In a previous study we found neither increased levels of erythrocyte sedimentation rate, C-reactive protein or acute-phase reactants nor clinical signs of a generalized inflammatory disorder. However, these tests may not be sensitive enough to detect a focal inflammatory process in the retro-orbital region. In the present study, we analysed serum levels of three soluble adhesion molecules; soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1) and soluble E-selectin (sE-selectin) in patients with episodic CH and in patients with biopsy-positive giant cell arteritis (GCA), a known vasculitic disorder of large and medium-sized arteries. A control group of healthy volunteers was also included. Within the CH group, sICAM-1, sVCAM-1 and sE-selectin showed an increasing trend in remission compared with the active CH period, but the difference was statistically significant for sE-selectin only. The mean sICAM-1 value was higher in patients with active GCA than in CH patients during the active cluster period. Compared with the healthy control group, the mean levels of soluble adhesion molecules in CH patients also tended to be higher, but statistically significantly so only for sVCAM-1. We hypothesize that CH is not a vasculitic disorder of the medium-sized arteries, but CH patients may have an immune response that reacts differently from that of healthy volunteers.     

Stability of soluble adhesion molecules, selectins, and C-reactive protein at various temperatures: implications for epidemiological and large-scale clinical studies

BACKGROUND: We assessed the impact of sample storage conditions on soluble vascular cell adhesion molecules (sVCAM), soluble intracellular adhesion molecules (sICAM-1), soluble (s)E-selectin, C-reactive protein (CRP), and sP-selectin. METHODS: Markers were measured by ELISA in venous blood from 10 healthy volunteers on aliquots stored as plasma or whole blood at 4, 21, or 30 degrees C for 1-5 days and after 1-5 freeze-thaw cycles. We compared results on these samples to results for samples processed immediately and stored at -80 degrees C. Statistical models assessed time-related effects and effects of postprocessing conditions. RESULTS: Using an upper limit of 10% variation from baseline with P >0.05, we found that stability duration in plasma was 5 days for sVCAM-1 and sICAM-1 and at least 2 days for sE-selectin at 4, 21, and 30 degrees C and 5 days for CRP at 4 and 21 degrees C and 1 day at 30 degrees C. Stability duration in whole blood was 5 days for sVCAM-1 and sICAM-1 and at least 2 days for sE-selectin at 4, 21, and 30 degrees C and 5 days for CRP at 4 and 21 degrees C and 2 days at 30 degrees C. sP-selectin was not stable in plasma or whole blood. sICAM-1, sVCAM-1, CRP, and sE-selectin were stable after 5 freeze-thaw cycles. CONCLUSIONS: sVCAM-1, sICAM-1, and CRP are stable in plasma or whole blood at 4 and 21 degrees C for at least 3 days and sE-selectin for 2 days. sP-selectin is not stable and therefore requires immediate assay.     

Metabolic syndrome aggravates the increased endothelial activation and low-grade inflammation in subjects with familial low HDL

BACKGROUND: Inhibition of cytokine-induced expression of adhesion molecules is one of the atheroprotective mechanisms of high-density lipoprotein (HDL). AIM: We investigated whether increased endothelial activation and low-grade inflammation are present in Finnish subjects with familial low HDL, and which factors contribute to the inflammatory parameters. METHOD: High-sensitivity C-reactive protein (hsCRP), soluble intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), and sE-selectin were measured in 91 subjects with low HDL-cholesterol from 41 low-HDL families and in 112 normolipidemic controls with comparable age- and gender distribution. Presence of the features of the metabolic syndrome (MetS) was recorded. RESULTS: sVCAM-1, sICAM-1, sE-selectin, and hsCRP were significantly higher in low-HDL subjects than in the controls (sVCAM-1: 560+/-147 ng/mL versus 496+/-95 ng/mL, P = 0.001; sICAM-1: 247+/-60 ng/mL versus 215+/-47 ng/mL, P<0.001; sE-selectin: 52+/-20 ng/mL versus 44+/-16 ng/mL, P = 0.022; and hsCRP: 1.73+/-2.05 mg/L versus 0.85+/-1.10 mg/L, P<0.001). Low-HDL subjects had increased body mass index (BMI) and waist, and elevated insulin and triglyceride levels. Adhesion molecules and hsCRP increased according to the number of the features of the MetS. CONCLUSIONS: The presence of the MetS in subjects with familial low HDL-cholesterol aggravates the low-grade inflammation and endothelial activation, and ultimately may add to the higher susceptibility for atherosclerotic disease in these individuals.     

Influence of age and dietary fish oil on plasma soluble adhesion molecule concentrations

Soluble forms of intercellular adhesion molecule-1, vascular cell adhesion molecule-1 and E-selectin (termed sICAM-1, sVCAM-1 and sE-selectin respectively) are found in the plasma, and are elevated during inflammatory conditions in which there is increased expression of the cellular forms of the molecules on endothelial and other cells. sICAM-1, sVCAM-1 and sE-selectin concentrations were measured in the plasma of 140 healthy Caucasian subjects aged between 18 and 75 years (100 males/40 females). sICAM-1 concentrations varied between 59.9 and 299.7 ng/ml (median 150 ng/ml), sVCAM-1 concentrations varied between 222.8 and 1672.9 ng/ml (median 662 ng/ml) and sE-selectin concentrations varied between 12.4 and 90.3 ng/ml (median 45.5 ng/ml). There were significant positive linear correlations between age and the plasma concentrations of sICAM-1 (r=0.580; P<0.001) and sVCAM-1 (r=0.392; P<0.001), which were retained when the effects of gender, body mass index and fasting plasma triacylglycerol and total cholesterol concentrations were controlled for. The significant positive linear correlation between age and the plasma concentration of sE-selectin (r=0.234; P=0.027) was lost when other variables were controlled for. Male subjects <40 years of age had significantly lower plasma concentrations of both sICAM-1 and sVCAM-1 than males >55 years of age (both P<0.001), but the difference in plasma sE-selectin concentrations between the age groups did not reach significance (P=0.073). Subgroups of 16 males aged <40 years and 12 elderly subjects (>55 years of age) participated in a doubled-blind, placebo-controlled study of fish oil supplementation over 12 weeks. The level of eicosapentaenoic acid in plasma phospholipids did not change with placebo supplementation, but was significantly increased with fish oil supplementation in both young male and elderly subjects (median increase 200%). sICAM-1, sVCAM-1 and sE-selectin concentrations were unaffected by supplementation with placebo in either young male or elderly subjects. sICAM-1 concentrations were unaffected by fish oil supplementation. sE-selectin concentrations were significantly increased by fish oil supplementation in young males (P=0.043; median increase 38%), but fish oil tended to decrease plasma sE-selectin concentrations in the elderly subjects (P=0.075), with a median decrease of 11%. sVCAM-1 concentrations were unaffected by fish oil supplementation in young males. Fish oil supplementation significantly decreased plasma sVCAM-1 concentrations in the elderly subjects (P=0.043), with a median decrease of 20% (range 16-60%). These observations suggest that fish oil decreases endothelial activation in elderly subjects.     

Circulating markers of endothelial function in cardiovascular disease

Endothelial dysfunction is a key event in cardiovascular disease. Measurement of endothelial dysfunction in vivo presents a major challenge, but has important implications since it may identify the clinical need for therapeutic intervention, specifically in primary prevention. Several biological markers have been used as indicators of endothelial dysfunction. The soluble adhesion molecules sICAM-1 and sVCAM-1 lack specificity and are increased in inflammatory processes. Both markers are increased in coronary artery disease. sICAM-1 level predicts the risk for cardiovascular disease or diabetes mellitus in healthy individuals. sE-selectin is specific for the endothelium and is increased in coronary artery disease and diabetes mellitus. sE-selectin is also associated with diabetic risk. The endothelium-specific marker, soluble thrombomodulin, is associated with severity of coronary artery disease, stroke or peripheral occlusive arterial disease and is not increased in healthy or asymptomatic subjects. Interestingly, thrombomodulin decreases during treatment of hypercholesterolemia or hyperhomocysteinemia. In contrast, von Willebrand factor is the best endothelial biomarker and predicts risk for ischemic heart disease or stroke.     

Increased levels of markers of vascular inflammation in patients with coronary heart disease

Elevated levels of soluble cell adhesion molecules (sCAMs), inflammatory cytokines and C-reactive protein (CRP) have been associated with atherosclerotic disease states. The aim of the present study was to evaluate whether circulating levels of vascular cell adhesion molecule-1 (sVCAM-1), intercellular adhesion molecule-1 (sICAM-1), E- and P-selectin were significantly elevated in patients with coronary heart disease (CHD) compared with healthy controls, and to study possible associations between these sCAMs, tumour necrosis factor alpha (TNFalpha). interleukin-6 (IL-6), CRP and major CHD risk factors. The study included 193 patients in various stages of CHD and 193 matched controls. To evaluate any possible influence of acute phase reaction, reinvestigation was performed after 6 months. After adjustment for major CHD risk factors, sVCAM-1, sICAM-1, P-selectin, IL-6 and CRP remained significantly elevated in the CHD patients (p for all <0.001). In multivariate analysis sVCAM-1 was predicted by age (p=0.015), sICAM-1 by smoking (p<0.001) and total cholesterol (p=0.026), E-selectin by body mass index (BMI) (p=0.004) and P-selectin by male gender (p=0.015). TNFalpha significantly predicted sICAM-1 and E-selectin levels, while IL-6 predicted CRP but none of the sCAMs measured. This might indicate that TNFalpha, but not IL-6, plays a major role in the regulation of sCAM levels in vivo.     

Adhesion molecule behavior during rejection and infection episodes after heart transplantation.

In cardiac transplant recipients the release of soluble cellular adhesion molecules intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-Selectin into serum is pronounced during immune activation. It is uncertain whether there is a specific pattern of release during infection or cardiac allograft rejection. In a prospective study, 30 consecutive cardiac allograft recipients were followed for a median period of 11.4 months (range 1-34). Soluble ICAM-1 (sICAM-1), soluble VCAM-1 (sVCAM-1) and soluble E-Selectin (sE-Selectin) were measured in addition to acute phase proteins (C-reactive protein, alpha1-antitrypsin), complement factors (C3, C4) and beta2-microglobulin. The measured serum levels were correlated with the clinical status of the transplant recipient: 1) uneventful clinical status; 2) asymptomatic infection; 3) symptomatic infection and 4) rejection. Forty age-matched healthy subjects served as controls. Six days before biopsy-proven cardiac allograft rejection sICAM-1-release started to increase (p < 0.05) as compared to uneventful clinical status. The peak concentration of sICAM-1 was measured three days before rejection. On the day of rejection, serum concentrations of sICAM-1 (p < 0.001) and sVCAM-1 (p < 0.05) were increased, whereas sE-Selectin was not markedly elevated. In symptomatic infections, the serum concentrations of sICAM-1 (p < 0.001) and sVCAM-1 (p < 0.05) were elevated at the day of diagnosis and both parameters reached peak levels three days after onset of chemotherapy. In multivariate analysis soluble adhesion molecules only weakly discriminated between rejection and infection (sensitivity: 13%, specificity: 95%). Although, in combination with routine blood parameters the discriminatory power could be improved (sensitivity: 85%, specificity: 85%) the clinical utility of these markers in non-invasive monitoring is limited.     

Adhesion molecules in untreated inflammatory arthritis: synovial expression and levels in synovial fluid and serum [corrected] [published erratum appears in QJM 1996 Jul;89(7):559]

Adhesion molecules play a critical role in regulating leucocyte migration at sites of inflammation. The relationship of soluble forms in serum or synovial fluid (SF) to synovial membrane expression in inflammatory arthritis is controversial. We examined soluble intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin levels in matched serum and SF, and their relationship to expression in synovium obtained at the same time in 13 patients with previously untreated inflammatory arthritis. Serum- soluble (s)ICAM-1 correlated with sedimentation rate (T = 0.45), Ritchie articular index (T = 0.47) and SF sICAM-1 (T = 0.48), and SF sICAM-1 correlated with membrane ICAM-1 expression (p < 0.02). sE- selectin and sVCAM-1 levels were unrelated to disease activity or membrane expression. Membrane E-selectin expression correlated inversely with ICAM-1 expression (T = -0.57) and serum sICAM-1 (T = - 0.54). Serum sE-selectin correlated inversely with membrane ICAM-1 expression (T = -0.55). The correlations observed between ICAM-1 in serum, SF, synovium and disease activity suggest that ICAM-1 could be a useful target for immunotherapy. The inverse relationship of ICAM-1 and E-selectin suggest important differences in regulation and pathogenetic roles.      

Increased levels of markers of vascular inflammation in patients with coronary heart disease

Elevated levels of soluble cell adhesion molecules (sCAMs), inflammatory cytokines and C-reactive protein (CRP) have been associated with atherosclerotic disease states. The aim of the present study was to evaluate whether circulating levels of vascular cell adhesion molecule-1 (sVCAM-1), intercellular adhesion molecule-1 (sICAM-1), E- and P-selectin were significantly elevated in patients with coronary heart disease (CHD) compared with healthy controls, and to study possible associations between these sCAMs, tumour necrosis factor &#102 (TNF &#102 ), interleukin-6 (IL-6), CRP and major CHD risk factors. The study included 193 patients in various stages of CHD and 193 matched controls. To evaluate any possible influence of acute phase reaction, reinvestigation was performed after 6 months. After adjustment for major CHD risk factors, sVCAM-1, sICAM-1, P-selectin, IL-6 and CRP remained significantly elevated in the CHD patients (p for all < 0.001). In multivariate analysis sVCAM-1 was predicted by age (p = 0.015), sICAM-1 by smoking (p < 0.001) and total cholesterol (p = 0.026), E-selectin by body mass index (BMI) (p = 0.004) and P-selectin by male gender (p = 0.015). TNF &#102 significantly predicted sICAM-1 and E-selectin levels, while IL-6 predicted CRP but none of the sCAMs measured. This might indicate that TNF &#102, but not IL-6, plays a major role in the regulation of sCAM levels in vivo .     

Clinical significance of circulating endothelial adhesion molecules (sE-selectin and sICAM) in untreated multiple myeloma patients

BACKGROUND: The expression of adhesion molecules is important for the interaction of myeloma cells with the bone marrow microenvironment. In the current study, serum soluble adhesion molecules (sICAM-1 and sE-selectin) were measured in untreated multiple myeloma (MM) patients in relation with other markers of disease activity. MATERIALS and METHODS: The study group consisted of 67 patients with MM (classified according to the Durie-Salmon classification) and 15 controls. Interleukin-6 (IL-6), sICAM-1 and sE-selectin concentrations were determined by enzyme-linked immunosorbent assay (ELISA). In addition, the monoclonal protein, erythrocyte sedimentation rate (ESR) and hemoglobin (Hb) concentration were also determined. RESULTS: Serum sICAM-1 level increased significantly at advanced stages of MM and was higher in comparison to controls (p<0.01). sE-selectin increased significantly with advancing stage of the disease, but did not differ from controls. IL-6, ESR and M-component were significantly higher and Hb concentrations lower with advancing stage of disease. There was a positive correlation of IL-6 with sICAM-1 and sE-selectin. CONCLUSIONS: We conclude that serum sICAM-1 differs in multiple myeloma patients from normals and together with sE-selectin increase in parallel to increasing stage of disease, which may reflect a dysregulation and possible involvement of these adhesion molecules in myeloma progression.     

Cell adhesion molecules as a marker reflecting the reduction of endothelial activation induced by glucocorticoids

In vitro, steroids down-regulate the expression of cell adhesion molecules (CAMs) in endothelial cells stimulated by lipopolysaccharide. Low-dose hydrocortisone is a new treatment of patients with septic shock, a state that is characterized by an endothelial injury. The aim of the present study was to investigate whether the plasma levels of soluble CAMs, reflecting in vivo endothelial activation, could be modulated in patients with septic shock treated by hydrocortisone. This was a prospective and observational study conducted in the intensive care unit at a university hospital. The subjects included 40 patients with septic shock (American College of Chest Physicians Consensus Conference/Society of Critical Care Medicine definition); 45 healthy blood donors served as controls. The patients receiving the standard care ("reference group") during the first 6 months were compared with the patients receiving the hydrocortisone therapy ("hydrocortisone group") for the next 6 months. Measurements of sCAMs were performed on days 1 and 3 of the disease. On day 1, sE-selectin, sP-selectin, sVCAM-1, and sICAM-1 were significantly elevated in patients with septic shock compared with healthy donors. sE-selectin levels significantly decreased between days 1 and 3 in the "hydrocortisone group," whereas there was no significant change in the "reference group". Surprisingly, sICAM-1 levels significantly increased between days 1 and 3 only in patients treated by hydrocortisone. No significant changes were observed for sP-selectin and sVCAM-1 levels in the two groups. In patients with septic shock, glucocorticoids differently affected the pattern of evolution of sCAMs, with sE-selectin being decreased and sICAM-1 being increased. Expression of sP-selectin and sVCAM-1 was not affected.     

Ethnic differences in circulating soluble adhesion molecules: the Wandsworth Heart and Stroke Study

The aim of this study was to investigate whether soluble adhesion molecule levels differ by ethnic group. Soluble plasma adhesion molecules [soluble P-selectin (sP-selectin), soluble E-selectin (sE-selectin), soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1)] were measured in 261 white (120 females), 188 African origin (99 females) and 215 South Asian (99 females) individuals living in England. All were free from coronary heart disease, stroke and other cardiovascular disease, diabetes, drug therapy for hypertension or high lipids, hormone-replacement therapy or oral contraceptive pill. The results of the study indicated that there were important differences in the levels of adhesion molecules by sex and smoking. However, when adjusting for these and other potential confounders, there were no differences in levels between white subjects and individuals of South Asian origin. In contrast, people of African origin had significantly lower levels of sICAM-1 [Caribbean -30% (-36 to -23%); West African -22% (-29 to -15%), values are means (95% confidence intervals)], sVCAM-1 [Caribbean -14% (-19 to -8%); West African -10% (-17 to -3%)] and sP-selectin [Caribbean -10% (-17 to -2%); West African -24% (-31 to -16%)] than white individuals. In conclusion, circulating levels of some soluble adhesion molecules are lower in individuals of Caribbean or West African origin compared with white or South Asian individuals. These relationships may contribute to the low risk of coronary heart disease seen in people of African origin living in England.     

糖尿病视网膜病变病人血清OX-LDL和CAMS浓度变化及意义

目的探讨糖尿病视网膜病变（DR）与血清氧化低密度脂蛋白（OX-LDL）和细胞黏附分子（CAMS）浓度变化的关系及临床意义。方法采用酶联免疫吸附测定法检测62例DR病人血清CAMS和OX-LDL浓度的变化,并与82例非DR（NDR）糖尿病病人及68例对照组进行比较,对32例增殖型DR（PDR）病人与30例非增殖型DR（NPDR）病人的血清CAMS和OX-LDL浓度进行比较。结果 DR病人血清OX-LDL和可溶性细胞间黏附分子-1（sICAM-1）、可溶性血管细胞间黏附分子-1（sVCAM-1）水平明显高于对照组和NDR病人（F=356.942-408.695,q=5.589-38.488,P〈0.001）;PDR病人血清OX-LDL和sICAM-1、sVCAM-1明显高于NPDR病人（t=6.156-15.078,P〈0.001）。DR病人血清OX-LDL与sICAM-1、sVCAM-1水平呈明显的正相关（r=0.524、0.660,P〈0.01）。结论血清OX-LDL与sICAM-1、sVCAM-1浓度变化参与了DR的发生与发展,且与病情严重程度有关。     

Circulating soluble adhesion molecules ICAM-1 and VCAM-1 and their association with clinical outcome, troponin T and C-reactive protein in patients with acute coronary syndromes

OBJECTIVES: The aim of this study was to compare concentrations of soluble intercellular adhesion molecule (ICAM-1) and vascular cell adhesion molecule (VCAM-1) in patients with coronary artery disease and healthy control and to evaluate the usefulness of the inflammatory markers as predictors of adverse prognosis in patients with acute coronary syndromes (ACS). DESIGN AND METHODS: ELISA was used to measure sICAM-1 and sVCAM-1 levels in 75 patients with ACS, 36 patients with stable angina pectoris (SAP) and 25 healthy subjects. hsCRP was measured with immunoturbidimetric assay, cardiac troponin T-with electrochemiluminescence immunoassay. RESULTS: All soluble ICAM-1 and VCAM-1 significantly discriminated between patients with ACS and SAP (p=0.014 and 0.05, respectively) and control subjects (p<0.001 and 0.05). During the 6-month follow-up of the patients with ACS, there were 28 major cardiac events (37.3%). The odds ratio associated with the highest value of sVCAM-1 was 4.62 (95% CI 1.8-11.4, p=0.0009) without adjustment and remained significantly elevated after adjustment for cTnT (RR 3.93, 1.5-10, p=0.04) and hsCRP (RR 2.22, 0.8-5.7, p=0.05). In contrast, an elevated level of sICAM-1 was not associated with future coronary risk after adjustment for cTnT and hsCRP. CONCLUSIONS: In patients with acute coronary syndromes, VCAM-1 serum levels powerfully predict an increased risk for subsequent cardiovascular events and extend the prognostic information gained from traditional biochemical markers.     

Evaluation of circulating vascular endothelial growth factor and soluble adhesion molecules as reliable predictors of native arteriovenous fistula thrombosis in chronic hemodialysis patients

ObjectivesWe evaluated the possibility of using circulating vascular endothelial growth factor (VEGF) and soluble adhesion molecules as reliable predictors of native arteriovenous (AV) fistula thrombosis in chronic hemodialysis (HD) patients.Design and methodsThis study included 62 HD patients (34 with thrombosed and 28 with non-thrombosed AV fistulas) and 21 healthy volunteers. Serum VEGF, soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1 (sICAM-1), and soluble E-selectin (sE-selectin) were measured using ELISA technique.ResultsVEGF, sVCAM-1, sICAM-1 and sE-selectin median levels were higher in HD patients compared to controls (p = 0.000 for all parameters). Increased median levels of VEGF and sVCAM-1 were demonstrated in HD patients with thrombosed AV fistulas compared to HD patients with non-thrombosed AV fistulas (p = 0.003 and 0.000, respectively). A significant positive correlation has been found between VEGF and sVCAM-1 in HD patients with thombosed AV fistulas (r = 0.525, p = 0.001).ConclusionsThe assessment of serum VEGF and sVCAM-1 might be useful for the identification of the chronic HD patients at an increased risk for native AV fistulas thrombosis. The clinical relevance of these observations warrants further investigations.     

C-反应蛋白细胞黏附分子与急性冠脉综合征相关性的临床研究

目的探讨急性冠脉综合征（ACS）患者体内C-反应蛋白（CRP）、可溶性细胞间黏附分子-1（sICAM-1）和可溶性血管细胞黏附分子-1（sVCAM-1）表达水平以及它们之间的相互关系。方法252例冠心病患者分为两组：ACS组86例，非ACS组166例。酶联免疫吸附试验（ELISA）法测定血清sICAM-1和sVCAM-1水平，快速免疫比浊法测定血清CRP水平。结果ACS组血清CRP、sICAM-1和sVCAM-1水平均显著高于对照组（P〈0．01），而且ACS组各类型血清CRP、黏附分子水平亦显著高于对照组（P〈0．05或P〈0．01）。结论血清sICAM-1、sVCAM-1、CRP对ACS的发生、发展可能起到促进作用，在ACS危险分层中具有一定临床意义。     

Markers of endothelial cell activation in elderly men at high risk for coronary heart disease

OBJECTIVE: Circulating cell adhesion molecules (CAMS) are regarded as inflammatory markers related to the process of atherosclerosis and cardiovascular disease (CVD). In the haemostatic system, elevated levels of thrombomodulin (TM), von Willebrand factor (vWF) and tissue-type plasminogen activator antigen (tPAag) have likewise been associated with atherothrombotic cardiovascular disease states. MATERIAL AND METHODS: Levels of these circulating markers were investigated in a cross-sectional study including 563 men aged 70 (64-76) years characterized as hypercholesterolaemic in 1972, as related to the following clinical entities: cardiovascular morbidity (28%), diabetes (15%), hypertension (70%) and smoking habits (34%) after 24 years. RESULTS: In patients presenting with CVD, significantly higher levels of tPAag were encountered (12.9 versus 12.0 ng/ml, p = 0.02). In smokers, levels of sICAM-1 were significantly higher (331 versus 298 ng/ml, p < 0.001), whereas levels of sVCAM-1 and sTM were lower compared with those in non-smokers (543 versus 582 ng/ml, p = 0.01, 40.6 versus 44.5 ng/ml, p < 0.01, respectively). In diabetics, levels of sE-selectin and tPAag were significantly higher than those in non-diabetics (55.9 versus 45.7 ng/ml, p < 0.001, 13.6 versus 12.0, p = 0.001, respectively). In subjects with hypertension, levels of TM were elevated (44.0 versus 40.8 ng/ml, p = 0.03). In multivariate regression analyses, tPAag remained significantly associated with the presence of CVD (p = 0.03), sE-selectin with diabetes (p=0.004), sTM with hypertension (p = 0.02) and sVCAM-1, sICAM-1 and sTM with smoking, (p = 0.01, p < 0.001, p < 0.001, respectively). CONCLUSIONS: The present results may contribute to the understanding of the multitude of factors influencing these endothelial markers and their evaluation in various disease entities.