Endothelial dysfunction and inflammatory process in transfusion-dependent patients with beta-thalassemia major

BACKGROUND: Beta-thalassemia major is associated with increased cardiovascular risk, although the underlying mechanisms remain unclear. We examined endothelial function and serum levels of inflammatory mediators in transfusion-dependent patients with beta-thalassemia major. METHODS: The study population consisted of 67 patients with homozygous beta-thalassemia major, (aged 24.6+/-0.7 years) and 71 healthy age and sex matched controls. Forearm blood flow was measured with gauge-strain plethysmography. Forearm vasodilatory response to reactive hyperemia (RH%) or to nitrate (NTG%) was expressed as the percentage change of forearm blood flow from baseline to the maximum flow during reactive hyperemia or sublingual nitroglycerin, respectively. Serum levels of interleukin 6 (IL-6), soluble vascular cell adhesion molecule (sVCAM-1) and soluble intercellular adhesion molecule (sICAM-1) were determined with ELISA. RESULTS: Patients had significantly lower levels of total cholesterol (125+/-4.5 vs. 207+/-7 mg/ml, p<0.01), ApoA1 (120+/-3 vs. 129+/-5 mg/ml, p<0.05), ApoB (60.5+/-2 vs. 95+/-4 mg/ml, p<0.01), ApoE (3+/-2 vs. 4+/-0.2 mg/ml, p<0.01) and Lp(a) (7.9+/-1.3 vs. 14.5+/-3.2 mg/ml, p<0.01) than controls. IL-6 levels were significantly higher in patients (3.03+/-0.31 pg/ml) than controls (1.15+/-0.15 pg/ml, p<0.01). Similarly, sVCAM-1 and sICAM-1 levels were significantly higher in patients (513+/-31 and 368+/-25.5 ng/ml, respectively) than controls (333+/-13.8 and 272+/-14.05 ng/ml, respectively, p<0.01 for both). Maximum hyperemic forearm blood flow and RH% were lower in patients (7.1+/-0.3 ml/100 ml tissue/min and 49+/-2.8%, respectively) than controls (8.26+/-0.32 ml/100 ml tissue/min and 86.3+/-5.57%, respectively, p<0.01 for both). CONCLUSIONS: Beta-thalassemia major is associated with impaired endothelial function and increased levels of IL-6, sVCAM-1 and sICAM-1, suggesting a potential role of inflammation and endothelial dysfunction in the complications of the disease.     

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.     

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.     

Longitudinal study of soluble intercellular adhesion molecule-1 (ICAM-1) in sera of patients with Graves' disease.

Adhesion molecules, such as Intercellular Adhesion Molecule-1 (ICAM-1), play an important role during the autoimmune process of Graves' disease (GD). So the objective of the study was to evaluate the time-course of the soluble ICAM-1 (sICAM-1) in GD. Concentrations of sICAM-1, thyroid hormones and TSAb (thyroid-stimulating antibodies) were determined in sera from 30 healthy controls, 41 untreated GD patients and after 3, 6, 12, 18 months of carbimazole therapy (no.=30), at relapse (no.=11) or 2 years after the end of therapy when remission (no.=13). Mean sICAM-1 concentration was significantly higher in untreated GD patients than in controls (mean+/-SD: 371+/-108 ng/ml vs 243+/-47 ng/ml, p<0.0001) until 6 months of therapy (289+/-102 ng/ml; NS). The number of positive patients (sICAM-1 levels>mean of the controls+2 SD) declined from 56% (23/41) at the time of the diagnosis to 10% (3/29) at 18 months. At relapse, mean sICAM-1 level significantly increased compared to that at 18 months of therapy (288+/-65 vs 236+/-59 ng/ml, p=0.005). At remission mean sICAM-1 level was significantly lower than in relapse patients (240+/-48 ng/ml, p=0.04); no patient displayed sICAM-1 positive values. In conclusion, sICAM-1 concentrations were increased in sera of newly diagnosed GD patients, declined significantly during carbimazole therapy and could again be increased at relapse. sICAM-1 could reflect an ongoing immune process and help to affirm the presence of an autoimmunity notably in some cases of TSAb negative patients. However its precise interest in clinical practice remains to be determined in further studies.     

Physical training reduces peripheral markers of inflammation in patients with chronic heart failure.

AIMS: Previous studies have shown an abnormal expression of cellular adhesion molecules and cytokines in chronic heart failure, which may be related to endothelial dysfunction characterizing this syndrome. Our study investigates the effects of physical training on serum activity of some peripheral inflammatory markers associated with endothelial dysfunction, such as granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage chemoattractant protein-1 (MCP-1), soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) in patients with chronic heart failure. METHODS AND RESULTS: Serum levels of GM-CSF, MCP-1, sICAM-1 and sVCAM-1 were determined in 12 patients with stable chronic heart failure (ischaemic heart failure: 6/12, dilated cardiomyopathy: 6/12, New York Heart Association: II-III, ejection fraction: 24+/-2%) before and after a 12-week programme of physical training in a randomized crossover design. In addition, the functional status of chronic heart failure patients was evaluated by using a cardiorespiratory exercise stress test to measure peak oxygen consumption. Physical training produced a significant reduction in serum GM-CSF (28+/-2 vs 21+/-2 pg. ml(-1), P<0.001), MCP-1 (192+/-5 vs 174+/-6 pg. ml(-1), P<0.001), sICAM-1 (367+/-31 vs 314+/-29 ng. ml(-1), P<0.01) and sVCAM-1 (1247+/-103 vs 1095+/-100 ng. ml(-1), P<0.01) as well as a significant increase in peak oxygen consumption (14.6+/-0.5 vs 16.5+/-0.5 ml. kg(-1)min(-1), P<0.005). A significant correlation was found between the training-induced improvement in peak oxygen consumption and percentage reduction in soluble adhesion molecules sICAM-1 (r=-0.72, P<0.01) and sVCAM-1 (r=-0.67, P<0.02). CONCLUSION: Physical training affects beneficially peripheral inflammatory markers reflecting monocyte/macrophage-endothelial cell interaction. Training-induced improvement in exercise tolerance is correlated with the attenuation of the inflammatory process, indicating that inflammation may contribute significantly to the impaired exercise capacity seen in chronic heart failure.     

Reduced concentrations of soluble adhesion molecules after antioxidant supplementation in postmenopausal women with high cardiovascular risk profiles--a randomized double-blind study

BACKGROUND: One of the suggested mechanisms of increased cardiovascular risk in postmenopause is a loss of the antioxidant effects of estrogens. It has been shown that classical cardiovascular risk factors increase oxidative stress on the arterial wall, and that endothelial cells react to this insult by increased expression of cellular adhesion molecules (CAM), which in turn are markers of arterial wall inflammation. METHODS: A randomized, placebo-controlled, double-blind study was performed in 60 postmenopausal women with high cardiovascular risk profiles, but free from clinical atherosclerotic disease. Patients were randomized to either antioxidant supplementation (using a combination of natural antioxidants; n = 30) or placebo (n = 30), and followed for 12 weeks. The concentrations of the adhesion molecules sVCAM-1 and sICAM-1 were measured by ELISA at baseline and at the end of the study, as well as total cholesterol, LDL, HDL, triglycerides and blood pressure. RESULTS: 27 women in the antioxidant supplementation group and 29 on placebo completed the study. At baseline, there were no significant differences in measured parameters between the groups: sICAM-1 concentrations were 341.8 +/- 116.9 vs. 349.9 +/- 104.6 ng/ml (active treatment vs. placebo; p = n.s.) and sVCAM-1 concentrations were 780.5 +/- 325.8 vs. 761.0 +/- 333.7 ng/ml (p = n.s.). In contrast, at the end of the study, sICAM-1 concentrations were 301.6 +/- 56.0 vs. 356.0 +/- 134.8 ng/ml (active treatment vs. placebo; p = 0.053) and sVCAM-1 concentrations were 656.0 +/- 326.5 vs. 818.5 +/- 381.0 ng/ml (p = 0.04). There were no significant differences between or changes within the groups in measured cholesterol and blood pressure. CONCLUSION: Antioxidant supplementation reduces serum concentrations of endothelium-derived adhesion molecules sICAM-1 and sVCAM-1 in postmenopausal women with high cardiovascular risk profiles.     

Circulating adhesion molecules in sera of asthmatic children

Infiltration of cells into the lung in asthma is regulated by several expressions of cell adhesion molecules (CAMs) on cells present in the airways, and may play a role in the pathogenesis of bronchial asthma. We sought to evaluate the role of serum concentrations of the soluble forms of intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), and E-selectin (sE-selectin) in the control of disease activity in acute asthma. Circulating levels of sICAM-1, sVCAM-1, and sE-selectin in sera from 15 normal control subjects and from 20 allergic asthmatic children with acute exacerbations who had returned to stable condition were determined by using commercially available enzyme-linked immunosorbent assay kits. The mean concentration of serum sICAM-1 levels was significantly higher during an acute exacerbation of asthmatic children than in those with stable asthma (19.41 +/- 10.65 ng/mL vs. 13.46 +/- 5.44 ng/mL; P < 0.001) or in control subjects (9.83 +/- 2.02 ng/mL; P < 0.001). For sVCAM-1 and sE-selectin, the mean serum concentration of sVCAM-1 was slightly higher in children during an acute exacerbation asthma than when stable. However, the differences did not reach statistical significance. The mean serum concentrations of sVCAM-1 and sE-selectin in acute asthma or stable asthma were significantly higher than in control subjects. This study provides further evidence that serum concentrations of sICAM-1, sVCAM-1, and sE-selectin are increased in acute asthma. These findings further confirm that leukocyte endothelial adhesion plays a role in inflammatory airway disease.     

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.     

Positive association of adiponectin with soluble vascular cell adhesion molecule sVCAM-1 levels in patients with vascular disease or dyslipidemia

The aim of our study was to evaluate the relationship of adiponectin to soluble forms of vascular cell adhesion molecule-1 (sVCAM-1) and intercellular cell adhesion molecule-1 (sICAM-1) in patients with cardiovascular disease or dyslipidemia. Two hundred and sixty-four patients (134 men/130 women, mean age 43.8+/-14.8/46.0+/-14.9 years) of Lipid Center, University Hospital Olomouc, off hypolipidemic therapy for at least 6 weeks, participated in the study. In multiple regression analysis, adiponectin was independently positively associated with serum HDL-cholesterol (p<0.0001) and sVCAM-1 (p<0.0001), female gender (p<0.0001) and negatively with hs-CRP (p=0.014). Serum concentration of adiponectin and sICAM-1 did not correlate but sICAM-1 was independently, positively associated with sVCAM-1 (p<0.0001) and negatively with markers of insulin resistance and inflammation, namely atherogenic index log[triglycerides/HDL-cholesterol] (p<0.0001), hs-CRP (p<0.001) and HOMA (p<0.05). Positive association of adiponectin with HDL-C and negative association with hs-CRP indicate anti-atherogenic properties of adiponectin. The finding of the positive association of adiponectin with sVCAM-1 in patients at risk is unexpected. We hypothesize that adiponectin may be involved (directly or indirectly) in shedding of ectodomains of VCAM-1 from endothelial surface and in this way down-regulates their effects. This process may be protective in the initial stages of atherosclerosis.     

Acute inflammatory state during influenza infection and endothelial function

Chronic inflammatory stimulus seems to contribute to atherosclerotic process. Several studies have established a relationship between infective agents as Chlamydia pneumoniae, herpes virus and cytomegalovirus and atherosclerotic lesions. Aim of this study was to investigate the effects of influenza infective state on endothelial function of healthy young subjects, expressed as brachial flow-mediated vasodilation (FMV) and soluble form of intercellular adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (sVCAM-1). In 10 male subjects (mean age 35+/-14 years) exhibiting influenza symptoms for 3 days, we determined total cholesterol, high-density lipoproteins (HDL), low-density lipoproteins (LDL), triglycerides, sVCAM-1, sICAM-1 and brachial FMV. All subjects had an antibody pattern characteristic of influenza A or B virus infection. After 3 months brachial FMV was significantly increased (8.6+/-2.3% versus 11.5+/-3.2%; p<0.001), while HDL (46+/-10 mg/dL versus 49+/-9 mg/dL; p<0.05), sICAM-1 and sVCAM-1 were reduced (respectively: 488+/-105 ng/mL versus 340+/-127 ng/mL; p<0.001, 1710+/-80 ng/mL versus 1216+/-63 ng/mL; p<0.001). Univariate analysis showed a positive correlation between changes in CRP and sICAM-1 levels (r=0.95, p<0.001), a negative one between changes in sICAM-1 and brachial FMV (r=-0.65, p<0.05) and between CRP and brachial FMV (r=-0.64, p<0.05). This small study suggested that inflammatory state determined by viral agents may transitorily alter endothelial function in healthy subjects.     

Plasma profiles of peripheral monocyte-related inflammatory markers in patients with arterial hypertension. Correlations with plasma endothelin-1

BACKGROUND: This study investigates the plasma activity of inflammatory mediators such as granulocyte-macrophage colony-stimulating factor (GM-CSF), C-C chemokines and soluble adhesion molecules, produced by monocyte-endothelial cell adhesive interaction, in patients with arterial hypertension. METHODS: We studied 66 untreated patients with mild to moderate arterial hypertension (hypercholesterolemic: 34, normocholesterolemic: 32) and 30 sex- and age-matched normocholesterolemic normotensive controls. Plasma concentrations of GM-CSF, macrophage chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1alpha (MIP-1alpha), RANTES (regulated on activation normally T-cell expressed and secreted), soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1), as well as plasma endothelin-1 (ET-1), were determined in study population by ELISA and RIA, respectively. RESULTS: Hypertensives exhibited significantly higher levels of GM-CSF (6.5+/-1.3 vs. 2.3+/-0.7 pg/ml, P=0.099), MCP-1 (175+/-31 vs. 120+/-24 pg/ml, P=0.0093), MIP-1alpha (23+/-4 vs. 15+/-2 pg/ml, P=0.0089), RANTES (17+/-4 vs. 14+/-3 ng/ml, P=0.047), sICAM-1 (235+/-39 vs. 187+/-21 ng/ml, P=0.0041), sVCAM-1 (684+/-42 vs. 589+/-23 ng/ml, P=0.0045) and ET-1 (6.1+/-1.5 vs. 2.4+/-0.3 pg/ml, P=0.0095) than those of normotensives. The normocholesterolemic hypertensives had significantly lower levels of GM-CSF, MCP-1, MIP-1alpha, sICAM-1 and sVCAM-1 than hypercholesterolemic hypertensives but higher than normotensives. In hypertensives, ET-1 levels were significantly correlated with mean arterial pressure (r=0.51, P=0.028), MCP-1 values (r=0.45, P=0.047) and sICAM-1 levels (r=0.64, P=0.0090). Significant correlations were also found between LDL cholesterol values and plasma inflammatory factors GM-CSF (r=0.58, P=0.0088), MCP-1 (r=0.49, P=0.040) and sICAM-1 (r=0.53, P=0.034) in the hypercholesterolemic sub-group of hypertensives. CONCLUSIONS: Inflammatory markers of monocyte-endothelial cell adhesive interaction are elevated in hypertensives in comparison to normotensives and may be related to plasma ET-1 activity. The coexistence of hypercholesterolemia may enhance this inflammatory process induced by arterial hypertension.     

Increased levels of soluble ICAM-1 in the plasma of sickle cell patients are reversed by hydroxyurea

Increased adhesive events between the blood vessel endothelium and red and white cells play a central role in the initiation of vasoocclusive crisis in sickle cell disease (SCD). Soluble VCAM-1 levels are increased in the plasma of sickle cell patients and may be reduced during hydroxyurea (HU) therapy. Reports regarding any changes in soluble ICAM-1 (sICAM-1) levels in sickle cell patients, however, are conflicting, and as yet no beneficial effect of HU upon levels has been observed. Thus, we sought to thoroughly investigate changes in sICAM-1 levels in SCD patients and the effect of HU therapy (20-30 mg/kg/day). Plasma sVCAM-1 levels were significantly higher in steady-state SCD patients than in normal controls (766 +/- 86 ng/mL vs. 325 +/- 38 ng/mL, respectively, P < 0.0001). sVCAM-1 levels were decreased in patients on HU therapy (543 +/- 69 ng/mL) compared to those not taking HU; however, this difference was not significant. Plasma sICAM-1 levels were significantly increased in steady-state SCD patients compared to normal individuals (285 +/- 20 ng/mL vs. 202 +/- 16 ng/mL, respectively, P = 0.002), and HU therapy significantly reduced sICAM-1 levels in patients (217 +/- 12, P = 0.027) to levels approaching those of healthy individuals. sVCAM-1 levels inversely correlated with fetal hemoglobin levels in SCD patients, while a nonsignificant inverse trend was observed between sICAM-1 levels and fetal hemoglobin. In conclusion, plasma sICAM-1 levels were significantly increased in SCD patients, and this increase was reversed by hydroxyurea therapy, possibly reflecting reduced endothelial activation in patients taking HU. Such an event may benefit patients by reducing adhesive interactions between white cells and the endothelium.     

Relation of the soluble cytoadhesion molecules VCAM-1 and ICAM-1 to selected clinical and laboratory indicators in multiple myeloma

Hitherto conducted studies concerned with the problem of cytoadhesive molecules (CAM) dealt only in a very limited way with the problem of multiple myeloma (MM). The subject of the submitted paper was evaluation of the relationship of soluble forms of "vascular cell adhesive molecule-1" (sVCAM-1) and "intercellular cell adhesion molecule-1" (sICAM-1) in serum from the peripheral bloodstream (PBS) and serum from a bone marrow aspirate (BMA) with selected clinical and laboratory indicators of MM (beta 2-microglobulin, thymidine kinase, immunochemical type of MM, S-creatinine, S-monoclonal immunoglobulin, S-albumin, Hb, percentage ratio of plasmocytes in bone marrow, age, performance status, stage and substage of MM and activity of disease) and proliferation characteristics of myeloma plasmocytes. The authors analyzed two groups of patients with MM, a group of 64 examined in different stages of MM and a group of 39 examined when the diagnosis of MM was established (median age 63 and 64 years, male/female ratio 1.6 and 1.3:1). The sVCAM-1 and sICAM-1 levels were examined by the ELISA method. Elevated values of sVCAM-1 in PBS were recorded in both groups in 87.5% and 87% patients, medians of sVCAM-1 exceeded the upper range of normal values (714 ng/ml) almost twice (1180 and 1295 ng/ml) whereby median values in BMA (1347 and 1546 ng/ml) were always somewhat higher than in PBS. Elevated sICAM-1 values in PBS were found in 35 and 33% patients, median levels of sICAM-1 in PBS and in BMA did not exceed the upper normal range (691 ng/ml) and did not differ substantially (518 vs. 476 and 518 vs. 500 ng/ml). Correlation analysis (Pearson's correlation coefficient and Mann-Whitney's test, p0.05) revealed in both groups a significant relationship of both CAM assessed in PBS and BMA (sVCAM-1 p-0.0000 and p-0.012, sICAM-1 p-0.0000 and p-0.0011). No relationship was found between sVCAM-1 and s-ICAM-1 levels assessed in PBS and BMA with proliferation indexes of myeloma plasmocytes, i.e. values of the propidium-iodide index PI/CD38 and PI/B-B4 (CD138). In the whole group of 64 patients a relationship was found between sVCAM-1 in PBS and values of S-creatinine (p - 0.004), Hb (p - 0.033), S-albumin (p - 0.035), S-beta 2-microglobulin (S-B2M) (p - 0.0000) and S-thymidine kinase (S-TK)(p-0.0000), when evaluating BMA, a relationship with B2M (p -0.011). In the group of 39 patients examined when the diagnosis of MM was made a relationship was found of sVCAM-1 in PBS to S-B2M) (p - 0.0000), S-TK (p-0.0000) and to S-creatinine (p -0.005), in BMA there was only a relationship with B2M (p - 0.020). In the whole group of 64 patients there was no relationship between s-ICAM levels in PBS with any of the examined indicators, when evaluating BMA only a relationship with B2M (p - 0.038) and TK (p - 0.022). In the group of 39 patients examined during the diagnosis of MM a relationship was found of sICAM-1 only with B2M in BMA (p - 0.013). In the total group of 64 a relationship was found between sVCAM-1 in PBS with the patient's age (p - 0.032) and the substage of MM(p-0.024), in the group of 39 patients a relationship between sVCAM on PBS and the substage of MM (p -0.031). On analysis of sICAM-1 a relationship was found between levels in BMA only with the patient's age (p -0.015). From the investigation ensued that despite evidence of a number of correlations between sVCAM and sICAM-1 levels and clinical and laboratory indicators of MM no relationship was found which could be applied under conditions of clinical practice. Assessment of levels of different indicators in serum of bone marrow aspirate did not reveal any advantages over examination in peripheral blood serum.     

Soluble adhesion molecules and marine n-3 fatty acids in patients referred for coronary angiography

OBJECTIVE: To investigate the relationship between soluble cellular adhesion molecules (sCAMs) and the extent of coronary artery disease (CAD) in patients with stable angina pectoris. METHODS AND RESULTS: Two hundred and ninety-one subjects had fasting levels of circulating intercellular adhesion molecule-1(sICAM-1), vascular cellular adhesion molecule-1 (sVCAM-1), sP-selectin and contents of n-3 polyunsaturated fatty acids (n-3 PUFA) in granulocyte membranes and adipose tissue determined before undergoing elective coronary angiography. Levels of soluble VCAM-1 (983+/-216 versus 893+/-196 ng/l, p<0.001), ICAM-1 (318+/-140 versus 290+/-75 ng/l, p<0.05) and P-selectin (90+/-27 versus 80+/-23 ng/l, p<0.01) were significantly increased in subjects with significant CAD compared to subjects with no significant stenoses. In a linear regression analysis, both sVCAM-1 and sP-selectin, but not sICAM-1, correlated to the presence and the severity of CAD. Both sICAM-1 and sP-selectin were significantly correlated to current smoking status and a history of myocardial infarction. The content of total n-3 PUFA and docosahexaenoic acid in adipose tissue was marginally, but significant positively correlated to VCAM-1. CONCLUSION: sVCAM-1 and sP-selectin may serve as markers of CAD in patients with stable angina pectoris. Only sVCAM-1 was weakly correlated to n-3 PUFA in adipose tissue.     

Serum levels of tumor necrosis factor-alpha, soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, and soluble interleukin-1 receptor antagonist in patients with thyroid eye disease undergoing treatment with somatostatin analogues.

The aim of this prospective, randomized study was to investigate the serum levels of tumor necrosis factor-alpha (TNF-alpha), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and soluble interleukin-1 receptor antagonist (sIL-1RA) in patients with thyroid eye disease (TED) before and 1 and 3 months after treatment with somatostatin analogues (SM-a). Thirty patients, all with signs and symptoms of TED, were studied. Twenty-two patients (13 females) had active eye disease with a clinical activity score (CAS) > or = 4 (patients with active disease [PA]) and 8 patients (5 females) had inactive TED with CAS < or = 3 (patients with inactive disease [PI]). All PA patients had a positive orbital octreoscan, whereas PI patients had a negative one. Fifteen patients from the PA group were selected randomly and received SM-a (PA-S subgroup), while the remaining 7 patients were used as control subgroup (PA-C), received neither therapy, nor placebo. From the 15 patients who received SM-a (PA-S), 6 received octreotide (OCT) and 9 lanreotide (LRT). TED was reevaluated using the CAS 1 and 3 months after the initiation of SM-a treatment. Ten healthy individuals (6 females) were used as controls (group C). We found an increase in the basal levels of TNF-alpha (14.2 +/- 7.1 pg/mL), sICAM-1 (809.1 +/- 167.0 ng/mL), and sIL-1RA (542.1 +/- 259.0 pg/mL) in PA patients as a total group compared with the PI (1.6 +/- 1.9, 676.8 +/- 73.4, 267.6 +/- 152.8, respectively) group and C (1.9 +/- 1.4, 598.0 +/- 126.2, 258.6 +/- 155.1, respectively). The basal levels of TNF-alpha (13.3 +/- 8.3 pg/mL) and sIL-1RA (533.7 +/- 308.9 pg/mL) in PA-S as well as in PA-C (16.0 +/- 2.9, 560.2 +/- 107.3, respectively) subgroups were also increased compared with PI patients and C (1.9 +/- 1.4 and 258.6 +/- 155.1, respectively). The same was true for sICAM-1 when baseline levels compared with C (817.1 +/- 187.3 and 791.9 +/- 123.5, respectively vs. 598.0 +/- 126.2 ng/mL). After SM-a, serum levels of sICAM-1 and sVCAM-1 were decreased significantly 1 (781.2 +/- 205.9, 1,193.5 +/- 511.8 ng/mL) and 3 months (786.8 +/- 199.6, 1,122.1 +/- 225.3 ng/mL) after the initiation of treatment. In conclusion, serum levels of TNF-a, sICAM-1, and sIL-1RA were elevated in patients with active TED compared to controls. Furthermore, sICAM-1 and sVICAM-1 levels declined during the treatment with SM-a in patients with active TED.     

Patients with essential hypertension present higher levels of sE-selectin and sVCAM-1 than normotensive volunteers

In essential hypertension (EH) patients, blood pressure can modify serum concentrations of some soluble forms of cell adhesion molecules (CAM), e.g., soluble E-selectin (sE-selectin) and soluble vascular cell adhesion molecule-1 (sVCAM-1). The objective of this study was to compare the serum levels of these CAMs in compensated (CH) and non-compensated (NCH) EH patients. Our findings show that sE-selectin and sVCAM-1 levels are higher in EH patients than normotensive subjects (sVCAM-1: 796+/-52 vs. 605+/-24 ng/mL, p<0.0001, and sE-selectin: 71+/-21 vs. 48+/-14 ng/mL, p<0.0001). Serum concentrations of both CAMs was higher in NCH patients than CH patients. High arterial blood pressure (ABP) may therefore increase the production of cell adhesion molecules, probably through endothelial activation.     

Influence of withdrawal of statin treatment on proinflammatory response and fibrinolytic activity in humans: an effect independent on cholesterol elevation

BACKGROUND: In addition to lowering lipid profile, statins have pleiotropic effects on improving vascular function. Changes of these pleiotropic effects and their relationship to lipid profile after withdrawal of statin treatment remained unclear. METHODS: We investigated the changes of lipid profile and plasma concentrations of human soluble vascular cell adhesion molecule-1 (sVCAM-1) and human tissue type plasminogen activator (tPA) after withdrawal of statin treatment. Twenty-two patients (14 F, 8 M, aged 63+/-13 years) with hypercholesterolemia were treated with atorvastatin (ATOR; 10 mg/day) for 12 weeks. Blood samplings for serum lipid and markers were collected before, after and withdrawal of statin treatment. RESULTS: The total cholesterol, LDL-cholesterol and sVCAM-1 (from 394.4+/-251.7 to 321.0+/-198.9 ng/ml, p<0.05) all decreased significantly and the tPA (from 9.47+/-3.57 to 11.62+/-3.99 ng/ml, p<0.05) increased significantly after atorvastatin treatment. During the following 3 days after withdrawal of atorvastatin, the total cholesterol and LDL-cholesterol did not show any significant change. However, the plasma sVCAM-1 significantly elevated on day 2 (from 321.0+/-198.9 to 371.2+/-220.4 ng/ml, p<0.05) and the plasma tPA significantly decreased on day 1 (from 11.62+/-3.99 to 10.52+/-3.55 ng/ml, p<0.05) and day 3 (from 11.62+/-3.99 to 10.27+/-3.69 ng/ml, p<0.05). Both the significant elevation of sVCAM-1 and decrease of tPA after withdrawal of atorvastatin treatment occurred within 3 days, while the serum cholesterol and LDL-chol levels did not have any significant change and were still within the therapeutic range. CONCLUSIONS: After 12 weeks of atorvastatin treatment, the beneficial pleiotropic effects can be demonstrated simultaneously with lowering the lipid profile. However, after withdrawal of atorvastatin, the beneficial pleiotropic effects are abrogated rapidly within days and are independent on elevation of serum cholesterol.     

Serum paraoxonase 1 activity is decreased in thyroid dysfunction

Changes in serum lipid and lipoprotein concentrations occur frequently in disorders of thyroid function. LDL-cholesterol (LDL-C) oxidation susceptibility is higher in these patients than in normal population. This study aims at assessing lipids, lipoproteins, apolipoproteins and serum paraoxonase 1 (PON1) activity in patients with thyroid dysfunction. Ninety-nine patients with thyroid dysfunction, (49 hypothyroid and 50 hyperthyroid) were compared with 2 separately age- and sex-matched control groups. A fasting blood sample was obtained and serum total cholesterol, triglycerides, apolipoproteins A-I and B, and PON1 activity were measured. In hyperthyroid patients, significantly lower PON1 activity (45 +/- 23 vs 67 +/- 37 IU/ml, p<0.001), triglycerides (112 +/- 53 vs 166 +/- 130 mg/dl, p<0.05), apolipoprotein A-I (137 +/- 26 vs 154 +/- 21 mg/dl, p<0.001) and apolipoprotein B (75 +/- 18 vs 86 +/- 25 mg/dl, p<0.05) were found. Hypothyroid patients had lower PON1 activity (46 +/- 21 vs 64 +/- 32 IU/ml, p<0.005) compared with controls, and higher total cholesterol (224 +/- 69 vs 185 +/- 41 mg/dl, p<0.001), LDL-C (133 +/- 59 vs 93 +/- 36 mg/dl, p<0.001), and apolipoprotein B (107 +/- 37 vs 84 +/- 23 mg/dl, p<0.001). The results show significant changes of lipid levels in thyroid dysfunction. In addition, a significant reduction in PON1 activity was observed in both hyper- and hypothyroid patients. Increased LDL-C oxidation in thyroid dysfunction observed in other studies, at least to some extent, can be attributed to reduced PON1 activity.     

Serum levels of selected adhesion molecules in patients with coronary artery disease

BACKGROUND: Adhesion molecules have been suggested as mediators of atherosclerotic inflammatory process. They may contribute to the pathogenesis of stable and unstable angina. METHODS: The study group consisted of 59 patients with coronary artery disease: 27 patients with stable exertional angina (group A), 32 patients with unstable angina (group B). 20 healthy persons acted as controls (group C). Serum levels of soluble Intercellular Adhesion Molecule 1 (sICAM-1), Vascular Cell Adhesion Molecule 1 (sVCAM-1), sE-selectin, sP-selectin were measured both before and after the treadmill ECG stress test in groups A and C. In group B the measurements were carried out at 6, 24, and 48 hours following an episode of chest pain. RESULTS: There were no differences between the baseline serum levels of adhesion molecules as determined in groups A and C. In patients with stable angina, the post-exercise concentrations of sE-selectin were significantly higher (68.8+/-29 ng/ml) in comparison to both baseline- (38.7+/-15 ng/ml), and group C-values (pre-exercise: 35.1+/-16; post-exercise: 49.9+/-15 ng/ml). In unstable patients, serum sP-selectin (190.1+/-99 ng/ml) and sVCAM-1 levels (1359+/-299 ng/ml) were higher when compared to those found in groups A (142.3+/-24; 962+/-352 ng/ml, respectively) and C (136.4+/-33; 851+/-168 ng/ml, respectively). CONCLUSIONS: Serum levels of soluble adhesion molecules in patients with stable angina are comparable to those of healthy persons. Stress test-induced increase of sE-selectin concentration may reflect endothelial response to exercise. Unstable angina is characterized by significant elevation of sP-selectin and sVCAM-1 serum levels which seems to be related to enhanced platelets and leukocytes activation.     

Clinical evaluation of serum concentrations of intercellular adhesion molecule-1 in patients with colorectal cancer

AIM: To investigate the correlation between the serum soluble intercellular adhesion molecule-1 (sICAM-1) and the clinicopathologic features and to evaluate the possible prognostic significance of sICAM-1 concentration in colorectal cancer. METHODS: A total of 56 patients (mean age 57.3 years) having transitional cell carcinoma of the colorectal and 25 control patients (mean age 42.6 years) were enrolled in the study. The serum samples of the patients were obtained on the day before surgery. Sera were obtained by centrifugation, and stored at -80 ℃ until assay. Serum concentrations of ICAM-1 were measured with enzyme-linked immunoassay. Differences between the two groups were analyzed by Student's t-test. RESULTS: No significant increase of serum sICAM-1 could be demonstrated in the Dukes A1 patients (352.63±61.82 μg/L) compared to the control group (345.72±49.81 μg/L, P>0.05), Dukes A1 patients (352.63±61.82 μg/L) compared to Dukes A2,3 patients (491.17±86.36μg/L, P<0.05). Furthermore, the patients with Dukes B had significantly higher serum concentrations of sICAM-1 than those of the control group (496.82±93.04 μg/L vs 345.72±49.81 μg/L, P<0.01). Compared with Dukes A2,3, B colorectal cancer patients, patients with more advanced clinical stage (Dukes C and D) had higher levels of sICAM-1 (743.68± 113.74 μg/L vs491.17±86.36 μg/L and 496.82±93.04 μg/L, P<0.001). The difference was statistically significant in sICAM-1 levels between patients with positive lymph node status and those without lymph node involvement (756.25±125.57 μg/L vs445.62±69.18 μg/L, P<0.001). Patients with poorly differentiated colorectal cancer had a higher level of sICAM-1 than those with differentiated and highly differentiated cancer (736.49±121.97μg/L vs410.23±67.47 μg/L,P<0.001). CONCLUSION: In this study, serum ICAM-1 levels were found to be related to tumor presence, clinical stages, and grade. Increased ICAM-1 in patients with colorectal cancer which should be considered when the diagnostic and/or prognostic usefulness of soluble ICAM-1 is to be evaluated. sICAM-1 should prove useful for monitoring malignant disease stage and for evaluating the effectiveness of various therapeutic approaches for colorectal carcinomas.