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.     

Elevated plasma asymmetric dimethylarginine levels in children with beta-thalassemia major may be an early marker for endothelial dysfunction

Objectives: Beta-thalassemia major is associated with the increased risk of cardiovascular morbidity and mortality. Asymmetric dimethylarginine (ADMA) has been implicated in the pathogenesis of endothelial dysfunction and atherosclerosis. In this study, we aimed to investigate circulating ADMA concentrations in children with beta-thalassemia major.

Methods: Thirty-one beta-thalassemia major children aged between 4 and 16 year old and age, gender-matched 36 healthy controls were enrolled in the study. Plasma ADMA was measured along with the soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1 (sICAM-1), P-selectin, and Pentraxin-3.

Results: Age, gender and body mass index were similar in two groups. Plasma ADMA, sVCAM-1, and sICAM-1 measurements were significantly higher in beta-thalassemia major patients than the control group (p?p?r?=?0.437, p?r?=?0.544, p?r?=?0.405, p?Discussion: The findings of the current study show us that increased plasma ADMA levels in children with beta-thalassemia major may be an early marker for endothelial dysfunction and may play a role in the development of premature atherosclerosis in beta-thalassemia major patients.     

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.     

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.     

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.     

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.     

Soluble intracellular adhesion molecules (sICAM-1, sVCAM-1) in peripheral blood of patients with thyroid cancer

The growth of a neoplasm and its ability to form metastases is a multistep process dependent on angiogenesis and immunological reactions of the organism. In this process adhesive factors are also involved. The aim of this work was estimation of the concentration of soluble intercellular adhesion molecules (sICAM-1) and vascular cellular adhesion molecules (sVCAM-1) in the serum of peripheral blood of patients with thyroid cancer before operation. The study comprised 48 patients ( 38 women and 10 men) aged from 18 to 87 years, in whom thin needle aspiration biopsy revealed cancer of the thyroid. Postoperative histopathological examination showed papillary cancer in 35 patients, oxyphilic cancer in 5 patients, anaplastic cancer in 4 and medullary cancer in 4 patients. In those patients, using the immunoenzymatic method ELISA, the concentration of sICAM-1 and sVCAM-1 in the serum of peripheral blood was determined. The control group comprised 26 healthy persons. We found statistically significant increase of sICAM-1 concentration in serum in all forms of cancer, in comparison with the control group. Mean concentrations of sICAM-1 were as follows: in papillary cancer patients 455.23+/-28.66 vs. 299.62+/-11.54 ng/ml, p<0.05; in oxyphilic cancer 455.60+/-95.21 vs. 299.62+/-11.54 ng/ml, p<0.05; in anaplastic cancer 570.00+/-170.89 vs. 299.62+/-11.54 ng/ml, p<0.05; and in medullary cancer 512.00+/-11.46 vs. 299.62+/-11.54 ng/ml, p<0.05. The mean concentration of sVCAM-1 in serum was statistically significantly higher than in the control group only in case of anaplastic cancer (1033.75+/-86.30 vs. 644.58+/-27.30 ng/ml; p<0.05). We evaluated the correlation coefficient between the concentration of sICAM-1 and sVCAM-1 in the serum of patients with thyroid cancer. Positive correlation was observed between the concentration of sICAM-1 and sVCAM-1. The obtained results confirm essential role of the investigated adhesive factors in the process of thyroid cancer growth.     

Racial difference in endothelial function: role of the infective burden

There is much evidence to suggest the existence of racial differences between blacks and whites in the behaviour of endothelial function. Infective state, sustained by viral or bacterial agents, may injure the endothelial surface favouring the onset and progression of atherosclerotic process, mainly by an inflammatory mechanism. The aim of the study was to investigate endothelial function, expressed as brachial flow-mediated vasodilation (FMV), in black and white healthy subjects, along with antibody titer to cytomegalovirus, hepatitis virus (B, C), herpes virus-1 and 2, Epstein-Barr, Chlamydia pneumoniae and the expression of adhesion molecules. We enrolled 22 young (mean age 27+/-8 years) healthy subjects of black race (10 males) and 20 healthy young subjects (10 males, mean age 28+/-9 years) of white race. Total infectious burden (TIB) was defined as the number of serological positive infections. Black subjects have a reduced brachial FMV (6.9+/-3.5% versus 11.6+/-3.0%, p<0.01) and increased values of hsCRP (0.35+/-0.15 mg/dL versus 0.07+/-0.08 mg/dL, p<0.05), white cells (8578+/-1041/mmc versus 5833+/-998/mmc, p<0.01) and adhesion molecules (respectively: sVCAM-1 945+/-142 versus 779+/-93, sICAM-1 534+/-107 ng/mL versus 325+/-80 ng/mL; both p<0.01) in comparison to white subjects. The total infectious burden in black race was significantly higher than in white race (5+/-1 versus 2+/-1, p<0.01). At the univariate analysis, brachial FMV was significantly related to the levels of adhesion molecules (respectively: sVCAM-1 r=-0.49; sICAM-1 r=-0.50, both p<0.05), hsCRP (r=-0.47, p<0.05) and white blood cells (r=-0.43, p<0.05). TIB was associated with brachial FMV (r=-0.64, p<0.05), sVCAM-1 (r=0.55, p<0.05) and hsCRP (r=0.47, p<0.05). At the multivariate analysis the only predictive variables for brachial FMV were hsCRP, TIB and brachial diameter (respectively: beta=-0.49, -0.19, -0.54, all p<0.05). This study confirms that endothelial reactivity is impaired in young African black patients; moreover its behavior is strictly related to the inflammatory state and to the total infectious burden.     

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.     

Improved glycaemia in type 1 diabetes results in decreased levels of soluble adhesion molecules with no change in serum adiponectin or most acute phase proteins.

AIMS: To investigate how reduction of hyperglycaemia affects acute phase serum proteins in poorly controlled type 1 diabetic patients. METHODS: 24 patients (age 31.7 +/- 2.0 years, HbA1c 9.3 +/- 0.2%, BMI 24.2 +/- 0.7 kg/m2, diabetes duration 15.3 +/- 1.7 years) participated in the study. The treatment was optimised for 16 weeks. Blood samples were taken at baseline and at the end of the study. 16 healthy age- and BMI-matched subjects were chosen for a control group. RESULTS: At baseline, the patients had higher C-reactive protein (CRP) (1.09, median [range 0.24-18.82] mg/l vs. 0.66 [0.18-2.46] mg/l, p < 0.02), mean adiponectin (16.06 +/- 1.31 vs. 8.85 +/- 0.93 mg/l, p < 0.001), ceruloplasmin (306 +/- 16.1 vs. 205.4 +/- 5.5 mg/l, p < 0.001), fibrinogen (3.41 +/- 0.26 vs. 2.38 +/- 0.07 g/l, p < 0.001), soluble intercellular adhesion molecule-1 (sICAM-1) (255.4 +/- 10.3 vs. 194 +/- 10.6 microg/l, p < 0.001), soluble vascular adhesion molecule-1 (sVCAM-1) (533.4 +/- 21.8 vs. 422.9 +/- 20.7 microg/l, p < 0.01) and interleukin-6 (2.89 +/- 0.49 vs. 1.35 +/- 0.30 ng/l, p < 0.01) concentrations than the controls. During intensified treatment, HbA1c decreased (to 8.5 +/- 0.2%, p < 0.001). This resulted in reduced sE-selectin (from 44.6 +/- 2.6 to 38.8 +/- 2.6 microg/l, p < 0.01), alpha-1-acid-glycoprotein (A1GP) (from 622.9 +/- 47.9 to 525.7 +/- 27.9 mg/l, p < 0.01), sICAM-1 (from 255.4 +/- 10.3 to 240.8 +/- 9.1 microg/l, p < 0.05) and IL-6 (from 2.9 +/- 0.5 to 2.1 +/- 0.4 ng/l, p < 0.01). Serum amyloid A (SAA) and CRP did not change 12.00 (0.7-222.0) vs. 12.00 (1.6-277.0) mg/l for SAA and 1.09 (0.24-18.82) vs. 1.09 (0.18-23.08) mg/l for CRP, baseline vs. treatment, respectively. CONCLUSIONS: Poorly controlled type 1 diabetic patients have increased values of adiponectin, CRP, ceruloplasmin, fibrinogen, sICAM-1, sVCAM-1 and IL-6. Reduction of hyperglycaemia results in decreased sE-selectin, A1GP, sICAM-1 and IL6, while other inflammatory factors including CRP, SAA and adiponectin are not affected.     

Evidence of vascular dysfunction in young patients with successfully repaired coarctation of aorta

It is well documented that in patients with coarctation of the aorta life expectancy is not normal even after successful coarctation repair (SCR), primarily due to cardiovascular events. We examined endothelial function in the forearm circulation, the mechanical properties and intima/media thickness in carotid and femoral arteries and the inflammatory process in normotensive patients, after coarctation repair. Fifteen patients, 29+/-2 years old, 12+/-2.9 years after SCR and 16 age- and sex-matched controls were enrolled in our study. Forearm blood flow was determined by gauge-strain plethysmography. Forearm vasodilatory response to reactive hyperemia was expressed as the %change from baseline to post-reactive hyperemia blood flow. High resolution ultrasound was used for determination of intima/media thickness and elastic properties of carotid and femoral arteries. Serum levels of soluble vascular adhesion molecule 1 (sVCAM-1), intercellular adhesion molecule 1 (sICAM-1), E-selectin, and interleukines 1b (IL-1b) and 6 (IL-6) were determined by ELISA. Reactive hyperemia was significantly decreased in patients compared to controls (p<0.01). Patients with SCR had higher intima/media thickness and decreased distensibility in the carotid arteries than controls (p<0.01 for both). Serum levels of sICAM-1, sSVCAM-1, E-selectin and IL-1b were higher in SCR group than in controls (p<0.05 for all). Adult patients after SCR have impaired endothelial function in the forearm circulation, increased intima/media thickness, decreased distensibility in the carotid arteries and increased levels of proinflammatory cytokines and adhesion molecules than healthy controls. These results may partly explain the high incidence of coronary artery disease in patients with repaired coarctation of the aorta.     

The levels of soluble adhesion molecules in diabetic and nondiabetic patients with combined hyperlipoproteinemia and the effect of ciprofibrate therapy

Cell adhesion molecules are thought to play a role in atherosclerosis. Several clinical trials have shown that fibrate treatment leads to a reduction in coronary events, although the mechanisms are not fully understood. Soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1 (sICAM-1) and soluble E-selectin plasma concentrations were measured in 10 obese dyslipidemic men (group A), in 10 obese dyslipidemic type 2 diabetic men without coronary artery disease (CAD) (group B), and in 10 dyslipidemic type 2 diabetic men with angiographically documented CAD (group C) before and after 12 weeks of treatment with ciprofibrate. Compared with nondiabetic dyslipidemic men, diabetic patients with CAD or without documented CAD had significantly increased levels of sVCAM-1 (512 +/-39 versus 750 +/-139 ng/mL; p<0.0001 and 566 +/-78 ng/mL; p<0.01, respectively) and sE-selectin (54.8 +/-6.9 versus 65.9 +/-8.8 ng/mL; p<0.001 and 62.6 +/-9.4 ng/mL; p=0.056, respectively). The levels of sICAM-1 were similar in all 3 groups. Multivariate analyses showed that the higher sCAM levels in patients occurred independently of lipoprotein levels. Waist circumference as a marker of abdominal adiposity was the only independent predictor of elevated concentrations of all 3 cell adhesion molecules in multivariate analyses. sE-selectin was associated with HbA1C levels (p<0.01) in diabetic men at baseline. After 12 weeks of ciprofibrate therapy, sVCAM-1 levels were reduced by 13.5 +/-2.1%, sICAM-1 levels by 11.8 +/-2.2%, and sE-selectin levels by 17.1 +/-3.5% (p<0.01 for all) with the greatest sE-selectin reduction in the diabetic subgroups (p<0.001). There was no correlation between the lowering of soluble adhesion molecules and the magnitude of lipid-lowering effect. An increased level of circulating adhesion molecules may be a mechanism by which dyslipidemia and/or diabetes mellitus promotes atherogenesis, and treatment with ciprofibrate may alter vascular cell activation.     

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.     

Effects of combined administration of vitamins C and E on reactive hyperemia and inflammatory process in chronic smokers

Purpose of this study was to investigate the effect of combined administration of antioxidant vitamins C and E on endothelial function and serum levels of inflammatory markers such as tumor necrosis factor (TNF-), interleukines 1b (IL-1b) and 6 (IL-6), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and E-selectin in chronic smokers. Forty-three smokers were randomly divided into four groups receiving vitamin C 2 g/day (group A), vitamin C 2 g/day plus vitamin E 400 IU/day (group B), vitamin C 2 g/day plus vitamin E 800 IU/day (group C) or no antioxidant treatment (group D), for 4 weeks. Forearm blood flow (FBF) was measured using venous occlusion strain gauge plethysmography. Forearm vasodilatory response to reactive hyperemia (RH%) was expressed as the percentage change from baseline to post reactive hyperemia blood flow. RH% was significantly increased in groups B (P<0.05) and C (P<0.01), but remained unaffected in groups A and D. Serum levels of IL-1b, IL-6, sVCAM-1 and sICAM-1 were significantly reduced in group C (P<0.05, respectively), but remained unaffected in groups A, B and D. Thus, short term administration of vitamins C (2 g/day) and E (800 IU/day) reduces serum levels of IL-1b, IL-6, sVCAM-1 and sICAM-1, and improves forearm vasodilatory response to reactive hyperemia in healthy young smokers, while monotherapy with vitamin C alone is ineffective.     

Soluble adhesion molecules (sICAM-1, sVCAM-1) and selectins (sE selectin, sP selectin, sL selectin) levels in children and adolescents with obesity, hypertension, and diabetes

The attachment of monocytes and lymphocytes to endothelial cells, which initiates atherosclerosis, arises under the influence of adhesion molecules. The preclinical phase of this disease lasts many decades, and this provides an opportunity for the presymptomatic detection of high-risk subjects. We evaluated levels of the adhesion molecules: sICAM-1 (soluble intercellular adhesion molecule 1), sVCAM-1 (soluble vascular adhesion molecule 1), sE selectin, sP selectin, and sL selectin in children with atherosclerosis risk factors (n = 123, mean age 15.1 years) (obese [n = 17], hypertensive [n = 25], obese with hypertension [n = 30], type 1 diabetic [n = 51]). Twenty-seven healthy children formed the control group, mean age 15.2 years. sICAM-1 was higher in the study group compared with control (314.1 +/- 61 vs 264.9 +/- 55 ng/mL, P < .01). The same was found for sVCAM-1 (513.7 +/- 187 vs 407.9 +/- 76 ng/mL, P < .05) and E selectin (86.04 +/- 33.6 vs 62.1 +/- 20.3 ng/mL, P < .01). sP-selectin and sL-selectin levels were not different compared with controls. E selectin correlated with body mass index (BMI; r = 0.18, P = .03), total cholesterol (r = 0.2, P = .016), and triglycerides (r = 0.22, P = .008). sICAM-1 correlated with BMI (r = 0.19, P = .019) and systolic blood pressure (r = 0.13, P = .045). In multiple linear regression analysis, sE selectin was found to be associated with triglycerides (R2 = 0.29, P = .045), sICAM-1 dependent on BMI (R2 = 0.58, P = .047), and sVCAM-1 dependent on total cholesterol (R2 = 0.51, P = .006). Elevated concentrations of sICAM-1, sVCAM-1, and E selectin were found in obese, hypertensive, and diabetic children. We conclude that endothelial activation appears in these children, and adhesion molecules are related to the earliest stages of atherosclerosis.     

Effects of combined administration of low dose atorvastatin and vitamin E on inflammatory markers and endothelial function in patients with heart failure

BACKGROUND: Heart failure has been associated with impaired endothelial function, increased inflammatory process and elevated oxidative stress status. Both statins and vitamin E separately improve endothelial function in patients with hypercholesterolemia and/or advanced atherosclerosis. AIM: To evaluate the effect of atorvastatin alone or in combination with vitamin E on endothelial function and serum levels of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha) and vascular cells adhesion molecule (sVCAM-1) in patients with ischemic heart failure. METHODS: Thirty-eight male patients with ischemic cardiomyopathy were randomly divided into three groups and received either atorvastatin 10 mg/day (n = 14), a combination of atorvastatin 10 mg/day plus vitamin E 400 IU/day (n = 12), or no statin or antioxidant treatment (n=12, controls) for 4 weeks. Forearm blood flow (FBF) was measured using venous occlusion strain-gauge plethysmography. Forearm vasodilatory response to reactive hyperemia (RH%) or to nitrate (NTG%) was defined as the percent change of FBF from rest to the maximum flow during reactive hyperemia or after nitrate administration, respectively. RESULTS: RH% was significantly improved in both the atorvastatin-treated (p < 0.01) and atorvastatin plus vitamin E groups (p < 0.05), but the increase was significantly higher in the atorvastatin-treated group (p < 0.05). Serum levels of IL-6, TNF-alpha and sVCAM-1 were decreased in the atorvastatin-treated group (p < 0.05 for all), but remained unaffected in the other two groups (p = NS for all). CONCLUSIONS: Low dose atorvastatin treatment improves endothelial function and reduces the expression of proinflammatory cytokines and adhesion molecules in patients with ischemic heart failure, an effect partly depressed by vitamin E.     

Serum uric acid correlates with extracellular superoxide dismutase activity in patients with chronic heart failure

Increased serum uric acid has been identified as an independent risk factor for cardiovascular disease. However, because of its antioxidant capacity, uric acid may play a beneficial role in endothelial function. This paradoxical relationship between uric acid and endothelial function in chronic heart failure patients remains poorly understood. Thirty-eight chronic heart failure patients (New York Heart Association functional class II-III, mean age 58+/-10 years and mean left ventricular ejection fraction 25+/-8%) and twelve age-and-sex-matched healthy controls were studied. Chronic heart failure patients showed higher uric acid levels (7.3+/-2.3 mg/dL vs. 6.1+/-0.2 mg/dL, p<0.05) and lower extracellular superoxide dismutase activity (136+/-36 U ml(-1) min(-1) vs. 203+/-61 U ml(-1) min(-1), p<0.01) and endothelium-dependent vasodilatation (4.0+/-1.6% v. 9.1+/-3.0%, p<0.01) when compared with control subjects. In chronic heart failure patients, correlations between both uric acid levels and extracellular superoxide dismutase activity (r=0.45; p<0.01), and uric acid and endothelium-dependent vasodilatation (r=0.35; p=0.03) were detected. These correlations were not observed in healthy individuals, suggesting a positive effect of uric acid on endothelial function partially mediated by modulation of extracellular superoxide dismutase activity in chronic heart failure.     

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.     

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.     

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.