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.     

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 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.     

Relationship between intracoronary and peripheral expression of soluble cell adhesion molecules

BACKGROUND: Elevated levels of soluble cell adhesion molecules (sCAMs) have been reported in various coronary artery disease processes. The principle stimulus for expression of sCAMs is believed to be an inflamed atherosclerotic plaque within the coronary vessel. The relationship between levels of sCAMs in the coronary circulation and the peripheral circulation has not been defined. The primary aim of this study was to define the relationship between levels of sCAMs sampled from the systemic circulation and from the coronary circulation. We also set out to document the acute expression of soluble CAMs following coronary angioplasty with or without stent implantation. METHODS: The coronary sinus was cannulated in patients undergoing LAD angioplasty. Samples were drawn from left coronary ostium (LCO) and coronary sinus (CS) and femoral vein simultaneously before, immediately after and 4 h after the PTCA procedure. Levels of sICAM-1, sVCAM-1, sE-selectin and sP-selectin were measured using ELISA technique. RESULTS: 10 patients (7 male/3 female, 61+/-11 y) entered the study. There was no significant difference in the levels of sICAM-1, sVCAM-1, sE-selectin and sPselectin whether sampled from left coronary ostium, coronary sinus or femoral vein at all time points. There was no significant change in the acute expression of sICAM-1, sVCAM-1 and sE-selectin following coronary angioplasty. Levels of sP-selectin fell significantly during the PTCA procedure (142+/-7 ng/ml to 64+/-6 ng/ml, P<0.001) but then rose again after 4 h and returned toward baseline levels at 24 h. CONCLUSION: Levels of soluble CAMs sampled in the systemic circulation directly reflect levels in the coronary circulation. Coronary angioplasty results in rapid fall in levels of sP-selectin which returns to normal within 24 h following the procedure.     

Cigarette smoking and inflammatory indices in coronary artery disease

BACKGROUND: Smoking-induced endothelial dysfunction may lead to inflammatory activation within a vascular wall mediated by cytokines and adhesion molecules. The aim of the study was to assess the relationship between the smoking status and serum levels of tumor necrosis factor (TNF) alpha, sTNFR 1 and 2 (soluble forms of TNF receptor), Interleukin (IL)-2, IL-10 and some selected adhesion molecules (AM): sE-selectin, sP-selectin, Vascular Cell AM-1 (sVCAM-1) and Intercellular AM-1 (sICAM-1) in patients with coronary artery disease (CAD). METHODS AND RESULTS: The study group consisted of 122 consecutive admissions with stable CAD (class II/III CCS): 31 current smokers (group I; mean age+/-S.E.M.: 53.8+/-1.6 years), 38 ex-smokers (group II; mean age+/-S.E.M.: 57.8+/-1.4 years) and 53 patients who have never smoked (group III; mean age+/-S.E.M.: 62.4+/-1.1 years). Serum concentration of IL-2 was higher in the group of active smokers (77.5+/-12.7 pg/ml) than in ex-smokers (40.0+/-10.6 pg/ml; P=0.017). AM determination also revealed differences between groups I and II-elevated serum sP-selectin levels in active smokers (174.7+/-17.1 ng/ml) than in ex-smokers (123.5+/-10.3 ng/ml; P=0.024). Serum sTNFR 2 level was higher in group III (2457.3+/-120.5 pg/ml) in comparison to group II (2018.4+/-121.5 pg/ml; P=0.006). There were no differences between TNF alpha, sTNFR 1, IL-10, sE-selectin, sICAM-1, sVCAM-1 levels in the groups examined. CONCLUSIONS: Cigarette smoking is associated with the elevation of IL-2 and sP-selectin serum levels in patients with stable CAD. CAD patients who have never smoked are characterized by delayed onset of angina and increased sTNFR 2 concentrations.     

High-density lipoprotein particles in octogenarians

High-density lipoprotein (HDL) particles exhibit considerable heterogeneity, specifically in apolipoprotein (apo) composition. Thus, apo A-I, the major protein of HDL, is present in two types of particles: one species contains both apo A-I and apo A-II (Lp A-I/A-II) while in the other (Lp A-I), apo A-II is absent. We used the hypothesis that octogenarians, who survived periods in life when the incidence of coronary heart disease (CHD) is very high, have several protective factors. We compared HDL-cholesterol (HDL-C), HDL2-cholesterol (HDL2-C), HDL3-cholesterol (HDL3-C), apo A-I, and apo A-II in octogenarians and younger control subjects smoking less than 10 cigarettes/d and not taking drugs known to affect lipid metabolism. Using a new procedure, we also compared the levels of Lp A-I and Lp A-I/A-II. The cholesterol content of total HDL was similar in octogenarian and control (38 +/- 8 years) men while HDL2-C was higher and HDL3-C, apo A-I, and A-II were lower in octogenarian than in control men. In women, the level of HDL-C and apo A-I was similar in premenopausal and octogenarian subjects but higher in postmenopausal women than in octogenarians, while HDL2-C and apo A-II were similar in the three groups. In contrast, HDL3-C was higher in the two groups of control women (premenopausal and postmenopausal) than in octogenarians. However, Lp A-I was significantly elevated in octogenarian men and women (men: 61 +/- 14 mg/dL; women: 70 +/- 14 mg/dL) by comparison with younger control subjects (men: 48 +/- 12 mg/dL; premenopausal women: 53 +/- 11 mg/dL; postmenopausal women: 63 +/- 19 mg/dL).(ABSTRACT TRUNCATED AT 250 WORDS)     

Leukocyte counts and concentrations of soluble adhesion molecules as predictors of coronary atherosclerosis

BACKGROUND: Authors of recent studies have reported that there is a relationship between level of adhesion molecules and atherosclerosis. In an animal study it was demonstrated that there is an interaction between adhesion molecules and leukocytes in atherosclerotic tissue. OBJECTIVE: To study the relationships between coronary-artery atherosclerosis and both differential blood-leukocyte count and concentrations of soluble adhesion molecules in patients with and without coronary artery disease (CAD). METHODS: Our subjects were 168 patients who underwent diagnostic coronary angiography. Forty-eight patients had normal coronary angiograms (control group), and 120 patients had significant coronary-artery stenoses (diameter stenosis > 70%) in at least one major coronary-artery branch (CAD group). Total and differential blood-leukocyte counts, and concentrations of soluble intercellular adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (sVCAM-1) were assayed prior to angiography. RESULTS: Monocyte counts for patients in the CAD group were significantly greater than those for patients in the control group (366 +/- 99 versus 258 +/- 44/microl, P < 0.0001), as were the sICAM-1 concentrations (272 +/- 52 versus 203 +/- 24 ng/ml, P < 0.0001). The mean concentrations of sVCAM-1 in members of the two groups were the same (671 +/- 138 versus 668 +/- 97 ng/ml, P=0.4). There was a higher incidence of significant coronary-artery stenosis among patients with both a high monocyte count and a high concentration of sICAM-1 (> or = mean + SD) than there was among patients with a low monocyte count and a low concentration of sICAM-1 (> or = mean - SD; 100 versus 25%, P < 0.0001). CONCLUSIONS: Higher levels both of monocyte counts and of serum concentrations of ICAM-1 may serve as markers for coronary atherosclerosis.     

Apolipoprotein A-II,HDL metabolism and atherosclerosis

Apolipoprotein (Apo) A-I and apo A-II are the major apolipoproteins of HDL. It is clearly demonstrated that there are inverse relationships between HDL-cholesterol and apo A-I plasma levels and the risk of coronary heart disease (CHD) in the general population. On the other hand, it is still not clearly demonstrated whether apo A-II plasma levels are associated with CHD risk. A recent prospective epidemiological (PRIME) study suggests that Lp A-I (HDL containing apo A-I but not apo A-II) and Lp A-I:A-II (HDL containing apo A-I and apo A-II) were both reduced in survivors of myocardial infarction, suggesting that both particles are risk markers of CHD. Apo A-II and Lp A-I:A-II plasma levels should be rather related to apo A-II production rate than to apo A-II catabolism. Mice transgenic for both human apo A-I and apo A-II are less protected against atherosclerosis development than mice transgenic for human apo A-I only, but the results of the effects of trangenesis of human apo A-II (in the absence of a co-transgenesis of human apo A-I) are controversial. It is highly suggested that HDL reduce CHD risk by promoting the transfer of peripherical free cholesterol to the liver through the so-called 'reverse cholesterol transfer'. Apo A-II modulates different steps of HDL metabolism and therefore probably alters reverse cholesterol transport. Nevertheless, some effects of apo A-II on intermediate HDL metabolism might improve reverse cholesterol transport and might reduce atherosclerosis development while some other effects might be deleterious. In different in vitro models of cell cultures, Lp A-I:A-II induce either a lower or a similar cellular cholesterol efflux (the first step of reverse cholesterol transport) than Lp A-I. Results depend on numerous factors such as cultured cell types and experimental conditions. Furthermore, the effects of apo A-II on HDL metabolism, beyond cellular cholesterol efflux, are also complex and controversial: apo A-II may inhibit lecithin-cholesterol acyltransferase (LCAT) (potential deleterious effect) and cholesteryl-ester-transfer protein (CETP) (potential beneficial effect) activities, but may increase the hepatic lipase (HL) activity (potential beneficial effect). Apo A-II may also inhibit the hepatic cholesteryl uptake from HDL (potential deleterious effect) probably through the SR-BI depending pathway. Therefore, in terms of atherogenesis, apo A-II alters the intermediate HDL metabolism in opposing ways by increasing (LCAT, SR-BI) or decreasing (HL, CETP) the atherogenicity of lipid metabolism. Effects of apo A-II on atherogenesis are controversial in humans and in transgenic animals and probably depend on the complex effects of apo A-II on these different intermediate metabolic steps which are in weak equilibrium with each other and which can be modified by both endogenous and environmental factors. It can be suggested that apo A-II is not a strong determinant of lipid metabolism, but is rather a modulator of reverse cholesterol transport.     

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.     

Elevated levels of circulating adhesion molecules in patients with active pulmonary tuberculosis

OBJECTIVE: Recent studies have indicated the importance of cell adhesion molecules in the pathogenesis of various inflammatory lung diseases. Our study was designed to determine whether five soluble adhesion molecules including soluble L-, E- and P-selectin (sL-, sE- and sP-selectin), intercellular adhesion molecule-1 (sICAM-1), and vascular cell adhesion molecule-1 (sVCAM-1) in serum reflect the severity of active pulmonary tuberculosis (TB), and whether there is a distinct profile of these soluble molecules in this disease. METHODOLOGY: Using enzyme-linked immunosorbent assays, we measured the serum levels of these five soluble adhesion molecules in 31 patients with active TB and 11 healthy volunteers. RESULTS: Serum levels of sE-selectin, sP-selectin and sICAM-1, but not sL-selectin or sVCAM-1, were significantly higher in patients with active TB than in the control subjects (P < 0.001, each). Significant correlations were detected only between serum levels of sE-selectin and sP-selectin, sE-selectin and sICAM-1, and sP-selectin and sICAM-1. There was a significant correlation between the Gaffky scale result (a scale assessing the number of mycobacteria bacilli present) and all of the above adhesion molecules, except for sL-selectin. Serum levels of sE-selectin, sL-selectin and sICAM-1 also correlated with the CXR radiological score. Higher levels of sL-selectin and sICAM-1 were detected in the serum of patients with radiological cavity formation compared to those without. The ESR, C-reactive protein and circulating neutrophil counts all correlated significantly with sE-selectin, sP-selectin, sICAM-1 and sVCAM-1. CONCLUSION: The results suggest that there is a distinct profile of soluble adhesion molecules in active pulmonary TB and that sE-selectin, sP-selectin, and especially sICAM-1 appear to be the most sensitive clinical measures of disease severity.     

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.     

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.     

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.     

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.     

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.     

Transcardiac gradient of soluble adhesion molecules predicts progression of coronary artery disease

BACKGROUND: During the development of atherosclerotic lesion, several types of cellular adhesion molecules (CAMs) are overexpressed on the surface of vascular endothelium. Some parts of these membrane proteins are proteolysed and are detected in blood as soluble forms. AIMS: The purpose of this study is to investigate the relationship between the transcardiac gradient of soluble cellular adhesion molecules (sCAMs) and the clinical characteristics of coronary artery disease (CAD). METHODS: We studied 46 patients with clinically stable CAD. Serum sCAM levels in both aortic sinus and coronary sinus were measured using enzyme-linked immunosorbent assay, and the transcardiac gradient of sCAMs was calculated. We also evaluated the angiographic severity of CAD, response of coronary artery to acetylcholine (Ach), as well as progression of coronary atherosclerosis over a 6-month period. RESULTS: The transcardiac gradient of sCAMs did not correlate to the angiographic severity of coronary atherosclerosis. The transcardiac gradient of sVCAM-1 was significantly higher in patients with vasoconstrictive response to Ach than patients without vasoconstrictive response to Ach (191.5+/-98.2 vs. -9.2+/-14.1 ng/ml, P<0.05). Furthermore, patients who exhibited progression of coronary atherosclerosis had a higher transcardiac gradient of sVCAM-1 at the initial study than patients without progression (47.8+/-24.5 vs. -6.4+/-12.3 ng/ml, P<0.05). CONCLUSIONS: An elevated transcardiac gradient of sVCAM-1 may represent the persistent activation of coronary artery that is accompanied by endothelial dysfunction, and may be a predictive index of progression of coronary atherosclerosis. Measurement of coronary circulating sVCAM-1 could provide important functional and predictive information about atherosclerosis.     

Soluble adhesion molecules in healthy subjects: a dose-response study using n-3 fatty acids

BACKGROUND AND AIM: Long-chain n-3 polyunsaturated fatty acids (PUFA) may protect against atherosclerotic disease, and serum levels of soluble cellular adhesion molecules (sCAMs) possibly reflect the inflammatory process underlying atherosclerosis. We studied the effect of n-3 PUFA dietary supplementation on the serum levels of sP-selectin, soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular adhesion molecule-1 (sVCAM-1), and the correlation between sCAMs and the fatty acid composition of granulocyte membranes. METHODS AND RESULTS: Sixty healthy volunteers were randomly assigned to receive a daily supplement of n-3 PUFA 6.6 g, n-3 PUFA 2.0 g, or olive oil for 12 weeks in a double blind design. A significant negative correlation was found between serum sICAM-1 levels and the DHA content of granulocyte membranes at entry. After supplementation with 6.6 g of n-3 PUFA, there was a significant decrease only in sP-selectin, which a gender subanalysis showed to be more marked in men. Among the women, there was a significant decrease in sICAM-1 in the PUFA 2.0 g group and a significant increase in sVCAM-1 in the PUFA 6.6 g group. CONCLUSIONS: The results indicate that high-dose supplementation with n-3 PUFA decreases sP-selectin levels in healthy subjects, thus suggesting a decrease in platelet reactivity or endothelial activation. However, the effect of n-3 PUFA on sCAMs is complex and may depend on gender and n-3 PUFA dose.     

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.     

Diurnal variation of soluble E- and P-selectin, and intercellular adhesion molecule-1 in patients with and without coronary artery disease

BACKGROUND: The more frequent onset of acute coronary syndromes (ACS) in the morning has been known for a long time. Diurnal changes of fibrinolysis such as lower activity of tissue plasminogen activator and higher activity of plasminogen activator inhibitor-1 (PAI-1) in the morning has been demonstrated previously and correspond with the manifestation of ACS. Less is known about the diurnal variation of soluble adhesion molecules as markers of endothelial or platelet activity in patients with coronary artery disease (CAD). PATIENTS AND METHODS: 80 patients with a history of myocardial infarction and/or chest pain with positive exercise testing admitted for elective coronary angiography were studied. 10 had normal findings on coronary angiography (control group), 70 patients had at least one or more stenoses >/=50% of the diameter of an epicardial vessel. None of the patients suffered from acute inflammation, connective or tumor disease. Blood samples were drawn at 7:00 a.m. and at 7:00 p.m. at rest and plasma concentration of soluble P-selectin (sP-selectin), E-selectin (sE-selectin), intercellular adhesion molecule-1 (sICAM-1) and acute-phase proteins were measured by ELISA. RESULTS: In both groups, no diurnal variation was found in sE-selectin and sICAM-1. sP-selectin levels were significantly higher in the evening (CAD group: 149.8 +/- 54.5 vs. 172.2 +/- 68.8 ng/ml, p < 0.001; control: 148.7 +/- 75.5 vs. 187.5 +/- 96.3 ng/ml, p = 0.001, Wilcoxon test). CONCLUSION: We have demonstrated diurnal variation of sP-selectin in patients with CAD. We conclude that high sP-selectin values in the evening represent the shed forms of the morning membrane-bound P-selectin.     

Soluble adhesion molecules in coronary artery bypass surgery

Plasma levels of sE-selectin, sP-selectin, and sICAM-1 were measured before anesthesia and at 0.5, 4, and 20 hours after cardiopulmonary bypass in 37 men undergoing coronary artery bypass surgery. Plasma sE-selectin remained close to the preoperative levels. The levels of sP-selectin increased significantly from 46.5 +/- 15.3 ng x mL(-1) to 69.3 +/- 39.6 ng x mL(-1) at 0.5 hours, 84.1 +/- 45.5 ng x mL(-1) at 4 hours, and 79.6 +/- 35.5 ng x mL(-1) at 20 hours. Plasma sICAM-1 levels decreased 0.5 hours after cardiopulmonary bypass, recovered at 4 hours, and showed a significant increase at 20 hours. The changes in plasma levels of adhesion molecules did not correlate with the duration of bypass or aortic crossclamping, hemodynamics, or creatine kinase-MB levels. However, sE-selectin and sICAM-1 levels increased considerably more in patients who needed norepinephrine in the intensive care unit. These results indicate that the transient changes in plasma levels of soluble adhesion molecules are not associated with postoperative myocardial injury in low-risk coronary grafting, although they correlate with the need for a vasopressor.