Increased levels of soluble adhesion molecules E-selectin and P-selectin in patients with cardiac syndrome X

The role of endothelial dysfunction and platelet activation in patients with cardiac syndrome X is controversial. The aim of this study was to investigate the plasma levels of circulating E- and P-selectin molecules in patients with syndrome X. The study included 21 patients with cardiac syndrome X (11 men and 10 women, mean age = 56 +/- 5 years) and 20 patients with significant coronary artery disease who had stable angina pectoris (11 men and 9 women, mean age = 60 +/- 8 years). Twenty-two age- and sex-matched subjects (12 men and 10 women, mean age = 58 +/- 8 years) undergoing diagnosis of atypical chest pain in whom coronary arteries were found normal and exercise test had no signs of ischemia served as the control group. Syndrome X was defined as presence of typical chest pain on exertion or at rest with positive exercise test and angiographically normal epicardial coronary arteries with no evidence of coronary spasm after intracoronary infusion of ergonovine maleate. The mean plasma concentrations of P-selectin were significantly elevated both in patients with coronary artery disease and syndrome X as compared with control subjects (49.15 +/-7.47 and 42.80 +/- 8.93 vs 22.63 +/-6.47 ng/mL, p < 0.001). Similarly, both patients with coronary artery disease and syndrome X had higher plasma concentrations of E-selectin than the control group (78.85 +/- 16.69 and 68.38 +/- 15.30 vs 36.43 +/- 4.72 ng/mL, p < 0.001). In conclusion, patients with syndrome X had increased plasma concentrations of soluble adhesion molecules, E-selectin and P-selectin, reflecting an ongoing chronic inflammation involved with endothelial dysfunction and enhanced platelet activation/damage in this setting.     

Association of soluble cell adhesion molecules and lipid levels in rheumatoid arthritis patients

Clinical Rheumatology - To evaluate the relationship between soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intracellular adhesion molecule-1 (sICAM-1), and lipid levels in rheumatoid...     

The effect of diet enriched with alpha-linolenic acid on soluble cellular adhesion molecules in dyslipidaemic patients

BACKGROUND: Leukocyte adhesion and transendothelial migration, the critical pathogenic components in the development of atherosclerotic lesions, are largely mediated by cellular adhesion molecules (CAMs). We examined whether dietary supplementation with alpha-linolenic acid (ALA, 18:3n-3) affects the levels of soluble forms of CAMs in dyslipidaemic patients. METHODS: We recruited 90 male dyslipidaemic patients (mean age=51+/-8 years) following a typical Greek diet. They were randomly assigned either to 15 ml of linseed oil (rich in ALA) per day (n=60) or to 15 ml of safflower oil (rich in linoleic acid [LA, 18:2n-6]) per day (n=30). The ratio of n-6:n-3 in linseed oil supplemented group was 1.3:1 and in safflower oil supplemented group 13.2:1. Dietary intervention lasted for 12 weeks. Blood lipids, soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1) and soluble E-selectin (sE-selectin) were measured. RESULTS: Dietary supplementation with ALA significantly decreased sVCAM-1 levels (median decrease 18.7% [577.5 ng/ml versus 487 ng/ml, P=0.0001]). In the LA supplemented group, sVCAM-1 was also significantly decreased but to a lesser extent (median decrease 10.6% [550.5 ng/ml versus 496 ng/ml, P=0.0001]). After controlling for smoking habits, no significant difference was observed in the reduction of sVCAM-1 levels between the two treatment arms (P=0.205). The decrease of sVCAM-1 was independent of lipid changes in both groups. CONCLUSIONS: Dietary supplementation with ALA for 12 weeks significantly decreases sVCAM-1 levels in dyslipidaemic patients. This effect presents a potential mechanism for the beneficial effect of plant n-3 polyunsaturated fatty acids in the prevention of coronary artery disease. In addition, dietary supplementation with LA significantly decreases sVCAM-1 levels, an effect which requires further investigation.     

Altered levels of soluble adhesion molecules in patients with rheumatoid arthritis complicated by peripheral neuropathy

OBJECTIVE: To assess levels of 2 circulating soluble adhesion molecules, vascular cellular adhesion molecule (sVCAM) and E-selectin, in patients with rheumatoid arthritis (RA) complicated by peripheral neuropathy compared to RA patients with no neurological complications and healthy controls. METHODS: In total, 25 RA patients with peripheral neuropathy (detected by clinical examination and confirmed by electromyography and nerve conduction studies), 40 RA patients without peripheral neuropathy, and 25 controls were studied. Clinical and laboratory assessments of disease activity were carried out and levels of sVCAM-1 and E-selectin were measured by ELISA in each of the 3 groups. RESULTS: Levels of sVCAM-1 and sE-selectin were higher (p < 0.001) in RA patients with peripheral neuropathy than in patients without neuropathy and controls. Levels of sE-selectin and sVCAM-1 correlated positively with disease activity variables. Correlation was independent of age and sex. CONCLUSION: Peripheral neuropathy in patients with RA is associated with increased endothelial cell activation evidenced by elevated serum levels of sVCAM-1 and sE-selectin in this group of patients.     

甲状腺疾病患者可溶性粘附分子的变化

利用酶联免疫法对168例Graves′病患者、36例桥本氏甲状腺炎患者、32例亚急性甲状腺炎患者和35例单纯性甲状腺肿患者和26例正常人测定血清中可溶性细胞间粘附分子（sICAM-1）和可溶性血管粘附分子（sVCAM-1）含量。结果以上五组sICAM-1依次为1105.1±106.7ng／ml、950.23±310.5ng／ml、786.23±462.4ng／ml、296.2±148.15ng／ml、342.5±250.2ng／ml。sVCAM-1依次为1760.6±403.7ng／ml、1231.7±110.6ng／ml;113.2±143.59ng／ml;941.3±95.4ng／ml;661.19±320.78ng／ml。说明不同的甲状腺疾病患者,其血清中粘附分子含量变化不同,并具有临床价值。     

The effect of cigarette smoking on soluble adhesion molecules in middle-aged patients with Type 2 diabetes mellitus.

AIMS: To investigate the effect of smoking on soluble adhesion molecules in middle-aged diabetic patients. METHODS: One hundred out-patients with Type 2 diabetes and 100 age- and sex-matched non-diabetic subjects without clinical macrovascular disease were selected. Soluble serum levels of adhesion molecules were analysed using enzyme immunoassay. Carotid atherosclerosis was assessed using an ultrasound system. RESULTS: When compared with non-diabetic subjects, soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1 (sICAM-1), and sE-selectin were found at significantly high levels in diabetic patients and significantly higher levels of sICAM-1, sE-selectin, and sP-selectin were observed in current smokers than never-smokers among diabetic or non-diabetic subjects, respectively. The combined, but not enhanced, effects of diabetes mellitus and smoking were observed in sICAM-1 and sE-selectin levels. Additionally, levels of sICAM-1 (P < 0.05) and sE-selectin (P < 0.01), but not sP-selectin, were high in ex-smokers when compared with never-smokers among diabetic patients. Diabetic smokers were also found to have marked carotid atherosclerosis, which was related to increased levels of sICAM-1. CONCLUSIONS: Our present study shows that levels of adhesion molecules were higher in diabetic smokers than diabetic non-smokers or non-diabetic smokers, and that cessation after chronic smoking did not restore the levels of sICAM-1 and sE-selectin, though sP-selectin levels were restored. These data suggest a possible mechanism for accelerated atherosclerosis induced by smoking in patients with diabetes.     

2型糖尿病肾病患者血清细胞粘附分子变化与氧化应激的关系

目的　探讨 2型糖尿病肾病患者 (DN)血清细胞粘附分子变化及其与氧化应激的关系。　方法　检测DN患者血清可溶性细胞间粘附分子 1(sICAM 1)、可溶性血管细胞粘附分子 1(sVCAM 1)、血清丙二醛 (MDA)含量和超氧化物歧化酶 (SOD)活性。　结果　早期DN及DN患者血清sVCAM 1水平〔分别为 (1 75± 0 48)、(1 91± 0 2 7)mg/L〕明显高于对照组〔(1 6 7± 0 72 )mg/L ,P <0 0 5和0 0 1〕 ,DN组明显高于单纯糖尿病 (DM)组〔(1 5 8± 0 39)mg/L ,P <0 0 5〕 ;DM组、早期DN组和DN组患者血清sICAM 1〔分别为 (75 6 0 0± 12 5 47)、(80 2 2 1± 12 4 81)、(897 6 0± 10 5 80 ) μg/L〕明显高于对照组〔(5 82 6 4± 10 2 73) μg/L ,P <0 0 0 1〕 ,其中DN组明显高于单纯DM组和早期DN组 (分别P <0 0 1和<0 0 5 ) ;单纯DM组、早期DN组和DN组患者血清SOD活性〔分别为 (86 5 9± 13 85 )、(85 6 9±11 32 )、(71 73± 16 35 )NU/L〕显著性低于对照组〔(92 73± 11 2 5 )NU/ml,P <0 0 1〕 ,MDA含量〔分别为(3 99± 1 36 )、(4 2 6± 1 95 )、(6 5 0± 2 98)nmol/ml〕显著性高于对照组〔(3 72± 0 5 7)nmol/ml,P <0 0 1〕。DM患者血清sVCAM 1与sICAM 1、收缩压、尿素氮 (BUN)和肌酐 (Cr)呈正相     

Plasma levels of soluble cellular adhesion molecules in patients with arterial hypertension. Correlations with plasma endothelin-1

Background: Several reports have shown that circulating, soluble cellular adhesion molecules and endothelin-1 (ET-1) are implicated in the pathophysiological events of atherosclerosis and may reflect the endothelial dysfunction characterizing this disorder. Methods: To evaluate the expression of these factors in arterial hypertension (AH), we measured plasma levels of soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble P-selectin (sP-selectin), and ET-1 in 60 untreated patients with mild to moderate AH (hypercholesterolemic: n=31, normocholesterolemic: n=29) and 30 sex- and age-matched normocholesterolemic normotensive controls. Results: Hypertensive patients exhibited significantly higher levels of sICAM-1 (234+/-21 vs. 187+/-12 ng/ml, P<0.005), sVCAM-1 (681+/-42 vs. 589+/-23 ng/ml, P<0.005), sP-selectin (89+/-17 vs. 55+/-11 ng/ml, P<0.01) and ET-1 (6.2+/-0.7 vs. 2.4+/-0.3 pg/ml, P<0.01) than did normotensive controls. The normocholesterolemic hypertensives had lower levels of sICAM-1, sVCAM-1 (P<0.01), sP-selectin and ET-1 (P<0.05) than hypercholesterolemic hypertensives, but higher levels than normotensive controls (P<0.05). In hypertensives, plasma ET-1 was significantly correlated with mean arterial pressure (r=0.51, P<0.03) and sICAM-1 levels (r=0.64, P<0.01). In hypercholesterolemic hypertensives, LDL cholesterol was also significantly correlated with plasma levels of sICAM-1 (r=0.53, P<0.04) and sP-selectin (r=0.41, P<0.05). Conclusions: Plasma levels of soluble cellular adhesion molecules are elevated in hypertensive patients in comparison to normotensive controls and may be related to plasma ET-1 activity. The coexistence of hypercholesterolemia may enhance the plasma soluble adhesion molecule activity induced by AH.     

可溶性黏附分子水平及阿卡波糖对不同糖耐量水平冠心病患者作用的观察

目的 通过检测不同糖耐量组冠心病（CHD）患者可溶性血管细胞黏附分子（SVCAM-1）、可溶性细胞间黏附分子（SICAM-1）和高敏C-反应蛋白（hs-CRP）水平,探讨不同糖代谢水平的CHD患者是否存在不同血管内皮功能和炎症状态,以及阿卡波糖对其的影响。方法根据OGTT结果将96例CHD患者分成糖代谢正常（NGT）组、IGT组和T2DM组,检测上述各组和对照（NC）组血清SVCAM-1、SICAM-1及hs-CRP浓度,对比与糖代谢各参数的相关性。观察阿卡波糖对IGT组和T2DM组SVCAM-1、SICAM-1、hs-CRP的影响。结果 IGT组和T2DM组血清SVCAM-1、SICAM-1、hs-CRP浓度高于其他组,血清SVCAM-1、SICAM-1与HbA1c（r=0.51、0.39,P〈0.01）及hs-CRP呈正相关（r=0.56、0.32, P〈0.01）。T2DM组SICAM-1与HbA1c、hs-CRP有更好的相关性（r=0.65、0.71, P〈0.001）。阿卡波糖治疗组比常规治疗组SVCAM-1、SICAM-1和hs-CRP浓度降低明显。结论 在CHD患者中,血清SVCAM-1、SICAM-1和hs-CRP浓度根据糖耐量水平的分组逐步升高,提示内皮受损、炎症状态可能是CHD合并糖代谢异常患者的重要的病理生理因素。阿卡波糖可能通过改善内皮功能和炎症状态,在CHD合并糖代谢异常患者治疗中起重要作用。     

冠心病患者可溶性细胞粘附分子的检测及其临床意义

目的 :检测冠心病 (CHD)患者可溶性细胞间粘附分子 1(sICAM 1)及P 选择素的变化 ,探讨其在CHD发病机制中的意义。方法 :用ELISA法和酶法分别检测 6 8例CHD患者和 5 5例对照者的血清sICAM 1、P 选择素、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇和甘油三酯 (TG)、总胆固醇水平 ,Gensini积分法评价冠状动脉病变程度 ,进行统计学分析。结果 :CHD患者血清sICAM 1和P 选择素水平均较对照组高 ,且差异有非常显著性意义 (均P <0 .0 0 1) ;sICAM 1水平与冠状动脉病变程度显著相关 (r =0 .6 6 2 ,P <0 .0 0 1) ;TG与sICAM 1水平呈正相关 (r =0 .4 0 3,P <0 .0 1) ;P 选择素与冠状动脉病变程度无明显关系。结论 :sICAM 1及P 选择素可能参与了CHD的发病过程 ,血清sICAM 1的检测有助于临床病情分析 ,TG是影响sICAM 1水平的因素之一。     

Leptin levels in diabetic and nondiabetic subjects

The role of leptin in human pathophysiology elicits considerable interest in view of its potential role as a treatment tool for obesity and other insulin resistant states, like type 2 diabetes mellitus (T2DM). Leptin has been extensively studied in obese humans, and much less so in other pathologic conditions. Leptin level has been reported to correlate with percent body fat mass (%FM), fasting serum insulin (FPI), insulin sensitivity and blood pressure. The aim of this study was to compare the leptin concentration, and its relationship with some anthropometric and biochemical parameters related to insulin resistance in 140 moderately obese type 2 diabetics (T2DM) and 160 age and weight matched non-diabetic controls in order to get a better insight into the possible role of leptin in the metabolic abnormalities of diabetes. The leptin levels were lower in the diabetic population only when both sexes were combined (p<0.05) and were higher in the females of both groups. Among the nondiabetics, the leptin levels appeared to be related to BMI, %FM, HDL and FPI, while this was not the case in the diabetics. After correction for BMI, leptin appeared to be correlated with the FPI levels only in the non-diabetic females. When plasma leptin was included in a multiple linear regression model with plasma leptin as a dependent variable, BMI, W:Hr and FPI levels were significantly related to leptin in the non diabetic population, while no relationship reached the level of statistical significance among the diabetics, with the exception of the borderline value for the FPI (p=.052). In conclusion, leptin levels were independent of any of the parameters examined in our diabetic population, possibly due to the progressive loss of the normal mechanisms of leptin regulation with advancing disease. Conclusive data can only be obtained from the longitudinal study of a cohort of newly diagnosed diabetic subjects.     

康复运动对心衰患者血浆可溶性粘附分子水平的影响

目的:通过观察充血性心力衰竭(CHF)患者运动训练前、后血浆可溶性细胞间粘附分子-1(sICAM-1)、血管细胞粘附分子-1(sVCAM-1)和E-选择素(sE-selectin)水平的变化,探讨其临床意义。方法:用ELISA法检测23例CHF患者6 min步行运动试验前、后血浆sICAM-1、sVCAM-1、sE-selectin水平,并以20例健康体检者作为对照,18例患者运动训练一个月后进行了随访。结果:CHF患者基础状态血浆sICAM-1、sVCAM-1和sE-selectin水平显著高于对照组(P<0.05-<0.01),且sICAM-1、sVCAM-1水平与心功能密切相关(P<0.05);运动后即刻sICAM-1、sVCAM-1水平较运动前升高(P<0.05),而sE-selectin水平运动前、后无显著性差异;康复训练一月后,无论基础状态还是运动后,sICAM-1、sVCAM-1水平较前次实验明显降低(P<0.05),而sE-selectin水平无显著性变化。结论:CHF患者血浆可溶性粘附分子水平较正常升高,6 min步行运动试验升高CHF患者血浆sICAM-1、sVCAM-1水平,接近日常生活活动强度的运动训练可降低该二者水平。     

Plasma soluble adhesion molecules; intercellular adhesion molecule-1, vascular cell adhesion molecule-1 and E-selectin levels in patients with isolated coronary artery ectasia

Plasma soluble adhesion molecules, intercellular adhesion molecule-1 (ICAM)-1, vascular cell adhesion molecule-1 (VCAM-1) and E-selectin leves of patients with isolated coronary artery ectasia (CAE), patients with obstructive coronary artery disease without CAE and subjects with angiographically normal coronary arteries were evaluated. Patients with isolated CAE were detected to have significantly higher levels of plasma soluble ICAM-1, VCAM-1 and E-selectin in comparison with patients with obstructive coronary artery disease without CAE (ICAM, 673 +/- 153 versus 381 +/- 106, respectively, P < 0.001; VCAM-1, 2366 +/- 925 versus 1136 +/- 208, respectively, P < 0.001; E-selectin, 74 +/- 21 versus 61 +/- 18, respectively, P = 0.01) and subjects with normal coronary arteries (ICAM-1, 673 +/- 153 versus 303 +/- 131, respectively, P < 0.001; VCAM-1, 2366 +/- 925 versus 729 +/- 231, respectively, P < 0.001; E-selectin, 74 +/- 21 versus 49 +/- 9, respectively, P < 0.001), suggesting the presence of a more severe and extensive chronic inflammation in the coronary circulation in patients with isolated CAE. BACKGROUND: The common coexistence of coronary artery ectasia (CAE) with coronary artery disease (CAD) suggests that it may be a variant of CAD. However, it is not clear why some patients with obstructive CAD develop CAE whereas most do not. Inflammation has been reported to be a major contributing factor to both obstructive and aneurysmatic vascular disorders and therefore, in the present study, the plasma soluble adhesion molecules, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin levels in isolated CAE were investigated. METHODS: The study population consisted of three groups: the first consisted of 32 patients with isolated CAE without stenotic lesion; the second of 32 patients with obstructive CAD without CAE; and the third group of 30 control subjects with normal coronary arteries. Coronary diameters were measured as the maximum diameter of the ectasic segment by use of a computerized quantitative coronary angiography analysis system. According to the angiographic definition used in the Coronary Artery Surgery Study, a vessel is considered to be ectasic when its diameter is > or =1.5 times that of the adjacent normal segment in segmental ectasia. Plasma soluble ICAM-1, VCAM-1 and E-selectin levels were measured in all patients and control subjects using commercially available enzyme-linked immunosorbent assay kits. RESULTS: Patients with isolated CAE were found to have significantly higher levels of plasma soluble ICAM-1, VCAM-1, and E-selectin in comparison with patients with obstructive CAD without CAE (ICAM, 673 +/- 153 versus 381 +/- 106, respectively; P < 0.001; VCAM-1, 2366 +/- 925 versus 1136 +/- 208, respectively; P < 0.001; E-selectin, 74 +/- 21 versus 61+/-18, respectively; P = 0.01) and control subjects with normal coronary arteries (ICAM-1, 673 +/- 153 versus 303 +/- 131, respectively;, P < 0.001; VCAM-1, 2366 +/- 925 versus 729 +/- 231, respectively; P < 0.001; E-selectin, 74 +/- 21 versus 49 +/- 9, respectively; P < 0.001). In addition, we detected statistically significant positive correlation between the total length of ectasic segments and the levels of plasma soluble ICAM-1 (r = 0.625; P < 0.001), VCAM-1 (r = 0.548; P = 0.001) and E-selectin (r = 0.390; P = 0.027). Multivariate logistic regression analysis revealed a significant independent relation between isolated CAE and ICAM-1 [odds ratio (OR) = 1.023; 95% confidence interval (CI) = 1.0048-1.0414; P = 0.0129] and VCAM-1 (OR = 1.0057; 95% CI = 1.0007-1.0106; P = 0.0240). CONCLUSIONS: We have shown that patients with isolated CAE have raised levels of plasma soluble ICAM-1, VCAM-1 and E-selectin in comparison with patients with obstructive CAD without CAE and control subjects with normal coronary arteries, suggesting the presence of a more severe and extensive chronic inflammation in the coronary circulation in these patients.     

Treatment of beta-thalassemia patients with recombinant human erythropoietin: effect on transfusion requirements and soluble adhesion molecules

The most common single genetic disorder and a major public health issue in Greece and other Mediterranean countries is beta-thalassemia. Current therapeutic approaches for homozygous beta-thalassemia entail blood transfusions and iron chelation therapy with deferoxamine or deferiprone for preventing tissue hemosiderosis. Recently, much effort has focused on various inducers of fetal hemoglobin (HbF) such as recombinant human erythropoietin (rHuEPO), especially in beta-thalassemia intermedia. Ten adult patients, 5 with beta-thalassemia major and 5 with beta-thalassemia intermedia, received 150 IU/kg rHuEPO (epoetin-alpha) subcutaneously three times a week. Seven patients were transfused every 14-30 days and 3 with beta-thalassemia intermedia were only occasionally transfused. The minimum duration of treatment was 12 weeks in order to define if there was any response. Transfusion intervals were modified according to the rHuEPO response to maintain stable Hb values. Lower transfusion requirements were observed in 5 patients after rHuEPO treatment (p = 0.028). In the 3 non-transfused patients, Hb values increased, and the patients are still being treated and followed up for a period ranging from 14 weeks to 2 years. Two patients with thalassemia major discontinued treatment after 12 weeks, as they did not achieve any response regarding transfusion requirements or Hb values. Pretreatment serum transferrin receptor levels were higher than in controls (p < 0.001) and significantly increased following rHuEPO treatment (p = 0.027). Patients had higher serum endothelin-3, sICAM-1 and sE-selectin values before rHuEPO treatment compared to controls (p < 0.001, p < 0.001 and p = 0.016, respectively), but these values were not altered during treatment. HbF values presented a slight, non-significant increase. rHuEPO treatment has a beneficial effect in transfusion-dependent beta-thalassemia patients. Although a slight increase in HbF levels was observed, other possible mechanisms are probably involved. None of our patients experienced thrombotic complications and a rise in blood pressure.     

The role of soluble cell adhesion molecules in patients with suspected deep vein thrombosis.

Activation of the endothelium, platelets and leukocytes has been shown to play an important role in the aetiology of deep venous thrombosis (DVT) in in-vitro experiments, resulting in the release of soluble cell adhesion molecules (sCAMs). We therefore assessed the value of soluble intracellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble E-selectin and soluble P-selectin for the diagnostic process in 69 consecutive patients with suspected DVT. Final diagnosis was based on the results of Duplex sonography or ascending venography. Thirty-seven patients (53.6%) finally suffered from DVT. Mean levels of sVCAM-1 were 589 +/- 530 ng/ml for controls and 587 +/- 328 ng/ml for patients. Corresponding levels concerning sICAM-1 were 316 +/- 161 and 342 +/- 186 ng/ml, those concerning soluble E-selectin were 54 +/- 38 and 42 +/- 18 ng/ml, and those concerning soluble P-selectin were 94 +/- 37 and 99 +/- 36 ng/ml (all P > 0.05). There was no significant correlation of the thrombus extension (all P > 0.05) or the duration of symptoms with sCAMs (all P > 0.05). In conclusion, we detected no significant differences concerning the concentration of four major sCAMs between patients with DVT and controls, so their assessment does not add any useful information for the diagnostic process of DVT.     

Serum levels of soluble adhesion molecules in stem cell transplantation-related complications.

To assess the involvement of vascular endothelial cell activation and damage in stem cell transplantation (SCT)-related complications, such as acute and chronic GVHD and thrombotic microangiopathy (TMA), we investigated the changes in serum levels of soluble forms of vascular cell adhesion molecule-1 (sVCAM-1) and E-selectin (sE-selectin) in SCT. The soluble form of intercellular adhesion molecule-1 (sICAM-1) was also analyzed. In patients with acute GVHD (grades II-IV), serum levels of sE-selectin and sICAM-1 increased around onset of GVHD (day 30). While the increase of sE-selectin levels was transient, sICAM-1 levels remained high until day 60. In patients with extensive chronic GVHD, sVCAM-1 as well as sE-selectin levels significantly increased. The appearance of clinical symptoms was preceded by elevations of sVCAM-1 and sE-selectin levels on day 60, and sICAM-1 levels on days 30 and 60. For the analysis of TMA, to exclude the influence of GVHD, serum levels were measured in auto-SCT patients. Around the onset of TMA, sVCAM-1 and sE-selectin levels significantly increased in patients with TMA without an increase of sICAM-1 levels. These findings support the notion that activation and injury of endothelium are commonly involved in the pathogenesis of acute and chronic GVHD and TMA.     

Comparison of serum concentrations of soluble adhesion molecules in diabetic microangiopathy and macroangiopathy.

AIMS: To clarify the correlation between serum concentrations of soluble adhesion molecules and diabetic microangiopathy or macroangiopathy in patients with Type 2 diabetes. METHODS: Patients with diabetic retinopathy and intima-media thickness of common carotid artery (CCA-IMT) < 1.1 mm were classified as the microangiopathy group (n = 62). Patients with CCA-IMT > or = 1.1 mm and without retinopathy were classified as the macroangiopathy group (n = 95). Patients with CCA-IMT < 0.9 mm and without retinopathy were assigned to the no complications group (n = 139). Clinical characteristics and soluble intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin levels were compared between the groups. RESULTS: Patients with microangiopathy had a significantly longer duration of diabetes, were hypertensive and more likely to have a positive family history of diabetes than the control group. Patients with macroangiopathy were more likely to be smokers, hypertensive, and have a family history of hypertension. Soluble ICAM-1, VCAM-1, and E-selectin levels were significantly higher in the microangiopathy group than in the control group. Soluble VCAM-1 and E-selectin levels, but not ICAM-1 levels, were significantly elevated in the macroangiopathy group. These results were unchanged after adjustment for age, sex, duration of diabetes, blood pressure, HbA1c, HDL-cholesterol, and smoking status. CONCLUSIONS: Our results suggest that soluble adhesion molecules are related to both diabetic micro- and macroangiopathy. The relative contributions of adhesion molecules may be greater in the former than latter patients with Type 2 diabetes.     

Increased levels of soluble adhesion molecules, E-selectin and P-selectin, in patients with infective endocarditis and embolic events.

AIMS: Inflammation-induced procoagulant changes and endothelial cell activation appear to play an important role in thromboembolic complications of infective endocarditis. Hence, the aim of this study was to compare the plasma levels of soluble adhesion molecules E- and P-selectin in infective endocarditis patients with and without embolic events, and healthy subjects. METHODS AND RESULTS: The study group consisted of 76 consecutive patients (mean age=26 years old, range from 8 to 64 years) with definite infective endocarditis according to the Duke criteria. Thirteen of the patients (17.1%) had embolic events. Transoesophageal echocardiographic examinations were performed on all patients within 3 days of initiation of antimicrobial therapy. Although there was a trend towards a higher rate of vegetations detected in those with embolic events than in those without, this did not reach statistical significance (84.6% vs 80.9%, P>0.05). Significantly larger vegetations were observed in patients with embolic events as compared to those without embolic events (1.4 cm vs 1.0 cm, P=0.03). The mean plasma concentrations of P-selectin were elevated in patients with embolic events as compared to both patients without embolic events and control subjects (58.69+/-7.49 ng x ml(-1)vs 29.65+/-5.69 ng x ml(-1), P=<0.001 and 58.69+/- 7.49 ng x ml(-1) vs 25.82+/-5.38 ng x ml(-1), P<0.001). Similarly, the patients with embolic events had increased plasma levels of E-selectin compared to those without embolic events and the control group (73.15+/-11.47 ng x ml(-1) vs 42.84+/-8.77 ng x ml(-1), P<0.001 and 73.15+/- 11.47 ng x ml(-1) vs 34.23+/-5.92 ng x ml(-1), P<0.001). CONCLUSION: Determination of these membrane activation molecules may provide useful markers with which to identify patients at high thromboembolic risk from infective endocarditis.     

Levels of soluble cell adhesion molecules in patients with angiographically defined coronary atherosclerosis

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+/-17ng/ml vs 247+/-19ng/ml, ns), and sP-selectin (142+/-8ng/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<0.05) relationships were observed between sVCAMs and serum levels of HDL3-cholesterol, apo A-II, and lipoprotein containing apo A-I and A-II, between sICAMs and levels of apo A-II and Lp A-I/A-II (Lp A-I/A-II), and between sP-selectin and lipoprotein containing only apo A-I. In conclusion, serum levels of soluble VCAM-1, ICAM-1, and P-selectin were not related to CHD or the extent of coronary atherosclerosis, but were inversely related to serum levels of high-density lipoprotein-related lipoproteins.     

西布曲明对单纯性肥胖患者血清可溶性粘附分子的影响

粘附分子在动脉粥样硬化的发生过程中发挥重要作用〔1〕。肥胖促进动脉粥样硬化的发生。已发现单纯性肥胖患者血清的可溶性粘附分子水平增高 ,经控制饮食减肥后 ,其水平降低〔2〕。为此 ,测定单纯性肥胖患者血清可溶性Ｅ 选择素、细胞间粘附分子 1(ＩＣＡＭ 1)、血管细胞粘附因子 1(ＶＣＡＭ 1)的水平 ,以及西布曲明减肥治疗对他们的影响。一、对象和方法1 .受试对象 :2 2例单纯性肥胖患者 (肥胖组 ) (男 6女16 ) ,体重指数 (ＢＭＩ)≥ 2 7ｋｇ/ｍ2 ,肝、肾功能正常 ,无糖尿病、高血压、心血管等疾病 ,排除继发性肥胖。口服盐酸西布曲明片…