Adhesion Molecules In Patients Research Articles

Relationship between Plasma Aldosterone Concentration and Soluble Cellular Adhesion Molecules in Patients Referred to Coronary Angiography

Evidence is emerging that aldosterone contributes to the development and progression of atherosclerosis and cardiovascular disease. Little is known, however, regarding an association between circulating aldosterone levels and soluble cellular adhesion molecules in humans. We investigated the relationship between plasma aldosterone concentration (PAC) and soluble cellular adhesion molecules in a large cohort of patients referred to coronary angiography. After exclusion of patients with ongoing mineralocorticoid receptor blocker use, oral contraceptive or hormone replacement therapy, 1,733 patients (mean age: 62.5±10.8 years; 26.4%% women; mean PAC: 101.5±93.5 pg/mL) remained eligible for analyses. Pearson correlation analysis as well as age and gender adjusted partial correlation analysis revealed a positive association between PAC and soluble (s) E-, L- and P-selectin levels but not with sICAM-1 and sVCAM-1, respectively. In multivariate adjusted analyses of covariance (ANCOVA) sE- (p=0.026), sL- (p=0.049) and sP-selectin (p<0.001) levels increased steadily from the first (reference) to the third gender-specific tertile of PAC. No significant variation across PAC tertiles was found for sICAM-1 (p=0.767) and sVCAM1 (p=0.425) levels, respectively. Finally, multivariate regression analyses revealed circulating aldosterone as an important predictor for soluble selectin levels. Our findings in a large cohort of patients indicate that upregulation of selectins might represent a novel mechanism of aldosterone mediated development and progression of atherosclerosis. In view of aldosterone as a novel cardiovascular risk factor independent of angiotensin II, our findings warrant further interventional studies which should evaluate anti-atherosclerotic effects of aldosterone blocking treatment strategies in humans.

The effect of atorvastatin therapy on tumour necrosis factor-α and vascular adhesion molecules in patients with type 2 diabetes mellitus with no prior history of coronary heart disease

We examined the effect of atorvastatin (and placebo) on tumour necrosis factor (TNF)α, soluble vascular cell adhesion molecule-1 (sVCAM-1) and soluble intercellular cell adhesion molecule-1 (sICAM-1) in patients with type 2 diabetes without prior cardiovascular disease (CVD) and investigated whether adhesion molecules were associated with incident CVD. Baseline and follow-up concentrations of TNFα, sVCAM-1 and sICAM-1 were measured in patients from the Collaborative AtoRvastatin Diabetes Study (CARDS). Patients had a mean age of 61 years (standard deviation = 8) and 70% were men. TNFα 2.20 pg/mL (1.82–2.86), sVCAM-1 865 ng/mL (729–1059) and sICAM-1 619 ng/mL (533–753) concentrations (median, interquartile range 25, 75%) were similar at baseline in atorvastatin (given values) and placebo groups and not significantly different at 2 years. The multivariable hazard ratios for the associations between sVCAM-1 and sICAM-1 (doubling the concentration) and CVD were, 0.82 (95% confidence interval (CI) 0.66–1.0) and 0.59 (95% CI 0.50–0.71), respectively. In conclusion atorvastatin had no significant effect on TNFα, sVCAM-1 or sICAM-1 levels in type 2 diabetic patients without a prior history of CVD compared with placebo. In addition, both sVCAM-1 and sICAM-1 concentrations were associated with a decreased risk of CVD.

Effects of short-term therapy with glibenclamide and repaglinide on incretin hormones and oxidative damage associated with postprandial hyperglycaemia in people with type 2 diabetes mellitus

Aim To examine the effects of glibenclamide and repaglinide on glucose stimulated insulin release, incretins, oxidative stress and cell adhesion molecules in patients with type 2 diabetes suboptimally treated with metformin. Methods A randomized clinical trial was performed recruiting 27 subjects (HbA 1c between 7.5 and 10.5%) free from cardiovascular and renal disease. Glucose, insulin, C-peptide, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), total antioxidant status, F 2-isoprostane, interleukin-6 and cell adhesion molecules were measured during an oral glucose load at baseline and after eight weeks of treatment. The areas under the curve were analysed at 45, 60 and 120 min (AUC 45, AUC 60, AUC 120). Results Significant improvements in glucose were observed with repaglinide (HBA 1c: −1.5%, fasting glucose: −2.8 mmol/L, 2-h glucose: −3.7 mmol/L, AUC 120: −18.9%) and glibenclamide (−1.0%, −2.2 mmol/L, −2.5 mmol/L, −17.5%). Repaglinide was also associated with an increase in the AUC 60 and AUC 120 for insulin (+56%, +61%) and C-peptide (+41%, +36%). GLP-1, GIP, IL-6, ICAM-1 and E-selectin levels did not change in either group. No association was observed between GLP-1, GIP-1 and plasma markers of oxidative stress. Conclusion Repaglinide is associated with improved postprandial glycaemic control via insulin and C-peptide release. We observed no direct effects of glibenclamide or repaglinide on plasma levels of GLP-1 or GIP. We observed no associations of GLP-1 and GIP with plasma markers of oxidative stress.

Anti-C1q antibodies have higher correlation with flares of lupus nephritis than other serum markers

Autoantibodies are important in the diagnosis and classification of systemic lupus erythematosus (SLE), but whether they correlate with changes in disease activity within individual patients is controversial. We assessed the association between changes in SLE global and renal activity and changes in several autoantibodies and cell adhesion molecules in patients with SLE. Stored sera collected at two or three clinic visits from each of 49 SLE patients (91% female, 59% African-American, 31% Caucasian, 10% other ethnicity, 38% under 30 years, 41% between 30-44 years, and 21% 45-63 years) were analyzed. The visits were chosen to include one visit with proteinuria, and one or two without, for each patient. Global disease activity was measured by the Physician's Global Assessment (PGA), SELENA-SLEDAI (SLE Disease Activity Index modified to exclude anti-dsDNA and complement) and renal activity assessed by urine protein (by urine dipstick) and Renal Activity Score. Sera were assayed for anti-C1q, anti-chromatin, anti-dsDNA, anti-ribosomal P, monocyte chemotactic protein-1 (MCP-1), vascular cell adhesion molecule (VCAM) intercellular adhesion molecule (ICAM) and complement. The associations between changes in disease activity and changes in biomarker levels were assessed. In terms of global disease activity, anti-C1q had the highest association with the PGA (p = 0.09) and was strongly associated with modified SELENA-SLEDAI (p = 0.009). In terms of renal activity, anti-C1q had the highest association with proteinuria (p = 0.079), and was strongly associated with Renal Activity Score (p = 0.006). Anti-C1q performed the best of the potential biomarkers, being significantly associated with the modified SELENA-SLEDAI and with the Renal Activity Score. This study indicates the potential superior utility of anti-C1q over anti-dsDNA and other measures to track renal activity.

Short-term atorvastatin preload reduces levels of adhesion molecules in patients with acute coronary syndrome undergoing percutaneous coronary intervention. Results from the ARMYDA-ACS CAMs (Atorvastatin for Reduction of MYocardial Damage during Angioplasty-Cell Adhesion Molecules) substudy

In patients with stable angina receiving percutaneous coronary intervention (PCI) prevention of periprocedural myocardial infarction by atorvastatin pretreatment was associated with reduction of endothelial activation. This mechanism was not evaluated in patients with acute coronary syndrome (ACS). The aim was to investigate effects of atorvastatin load on adhesion molecules in ACS patients undergoing PCI. In a planned subanalysis of the ARMYDA-ACS trial, a subgroup of 44 patients were blind-tested for measurement of intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin plasma levels; 21 patients belonged to the atorvastatin (80 mg 12 h before PCI, with a further 40 mg preprocedure dose) and 23 to the placebo arm. Adhesion molecules were evaluated at randomization (12 h before intervention), immediately before PCI and after 8 and 24 h. Reduction of procedural myocardial injury after statin pretreatment was confirmed in this subgroup. ICAM-1, VCAM-1 and E-selectin levels were similar at randomization and before intervention in both arms. At 8 h, ICAM-1 increase was similar in the two arms, whereas 24-h levels were lower in the atorvastatin vs. placebo group (241 ± 25 vs. 261 ± 30 ng/ml; P = 0.019). Significant attenuation of VCAM-1 elevation occurred both at 8 and 24 h in the atorvastatin group (509 ± 56 vs. 545 ± 59 ng/ml; P = 0.044 and 561 ± 58 vs. 600 ± 53 ng/ml; P = 0.025). E-selectin levels were not different at any time-point in the two arms. In ACS patients undergoing PCI, reduction of procedural myocardial injury after atorvastatin load is associated with attenuation of endothelial inflammatory response. This may contribute to mechanisms of statin cardioprotection in this setting.

Análisis comparativo de la expresión de moléculas de adhesión celular en linfomas cutáneos (micosis fungoide/síndrome de Sézary) y dermatosis inflamatorias mediadas por células T

Introduction Cell adhesion molecules play a pivotal role in the establishment of T-cell populations in the skin. In this study, we quantify the expression of cell adhesion molecules in patients with cutaneous T-cell lymphoma (CTCL) and compare it with the expression found in other skin diseases. Material and methods Frozen material was obtained from 42 patients in 5 different groups: early CTCL, comprising patients with patch- and plaque-stage of mycosis fungoides ( n=11); advanced CTCL ( n=7), comprising patients with mycosis fungoides ( n=3) and Sézary syndrome ( n=4); inflammatory skin disease ( n=12), comprising patients with psoriasis ( n=9) and atopic dermatitis ( n=3); chronic skin diseases with persistent plaques that do not fulfil the histological criteria for mycosis fungoides (pre-CTCL) ( n=8); and healthy volunteers ( n=4). Expression of the following cell adhesion molecules was analyzed: lymphocyte function-associated antigen 1, intercellular adhesion molecule 1 (ICAM-1), ICAM-3, cutaneous lymphocyte-associated antigen, E-selectin, very late antigen 4, vascular cell adhesion molecule 1, alphaEbeta7 integrin, and E-cadherin. Results The immunohistochemical analyses used here revealed statistically significant differences between CTCL and other skin diseases but not between early and advanced CTCL. The expression of alphaEbeta7 integrin and ICAM-3 in the epidermis per high-power field (400× magnification) allowed the different groups to be distinguished from each other, except for advanced CTCL and pre-CTCL. There were statistically significant differences between advanced CTCL and pre-CTCL in terms of the expression of E-selectin at 400× magnification and the expression of ICAM-1 in a honeycomb pattern in epidermal keratinocytes. Conclusions The expression of cell adhesion molecules involved in the adhesion and migration of lymphocytes in the skin does not differ significantly between initial and advanced stages of CTCL.

Cytokines and soluble adhesion molecules in children and adolescents with a tic disorder

Aim Dysregulation of the immune system may play a role in tic disorders. We screened for immune disturbances by investigating serum levels of cytokines and soluble adhesion molecules in patients with a tic disorder. Methods Serum levels of interleukin (IL)-2, IL-4, IL-5, IL-10, IL-12, soluble IL-2 receptor (sIL2R), tumor necrosis factor (TNF)-α, interferon (IFN)-γ, soluble vascular cell adhesion molecule-1 (sVCAM-1), and intercellular adhesion molecule-1 (sICAM-1) of 66 children and adolescents with a tic disorder and 71 healthy volunteers were compared. We also addressed possible relations between concentrations of the immune markers and severity of tics and comorbid obsessive–compulsive symptoms. Results Median serum concentrations did not differ significantly between patients and healthy subjects. Serum IL-2 concentrations were positively associated with tic severity ratings; serum IL-12 concentrations negatively with severity ratings of obsessive–compulsive symptoms. Conclusions These preliminary findings do not reveal major immune activation in children with a tic disorder but may suggest more subtle disturbances related to disease expression.

A prospective, comparative study on the early effects of local and remote radiation therapy on carotid intima–media thickness and vascular cellular adhesion molecule-1 in patients with head and neck and prostate tumors

Background and purposeTo investigate early vascular changes related to carotid atherosclerotic injury post-radiation therapy (RT), we studied carotid intima–media thickness (IMT) and vascular cellular adhesion molecule (VCAM)-1 at two time-points after RT and compared local and remote irradiation effects in patients with head and neck (HNC) and prostate cancer (PC), respectively. Material and methodsWe prospectively studied patients beginning RT for HNC or PC, performing carotid ultrasound before RT, early after and six months after treatment to measure carotid IMT. Blood samples were simultaneously collected to study VCAM-1 by ELISA. ResultsWe studied 19 patients with HNC and 24 with PC. Patients with HNC were younger (55±10years) than PC patients (68±8years). Early post-RT only HNC patients had an increase in IMT compared to baseline measurements (0.73±0.04mm vs. 0.80±0.05mm, p=0.029). On the other hand, VCAM-1 levels decreased in PC patients, remaining unchanged in HNC patients. Late post-RT (six months from previous assessment), neither IMT nor VCAM-1 values changed in both groups. ConclusionLocal and remote RT seem to exert differential early effects regarding vascular-related changes: (1) local RT seems to affect vascular structure and increase IMT and (2) RT for PC is associated with reduction in VCAM levels, suggesting systemic modulation of cancer-related factors.

Association between macular microcirculation and soluble intercellular adhesion molecule-1 in patients with macular edema and retinal vein occlusion

In patients who have macular edema secondary to retinal vein occlusion, the role of vasoactive molecules such as growth factors and the influence of molecules related to leukocyte adhesion need to be investigated further. A prospective study was performed to investigate the relations between perifoveal capillary blood flow velocity and the vitreous levels of vascular endothelial growth factor (VEGF) and soluble intercellular adhesion molecule-1 (sICAM-1) in patients with macular edema and retinal vein occlusion. Undiluted vitreous specimens were obtained from 11 eyes of 11 patients with macular edema (nine had branch retinal vein occlusion and two had central retinal vein occlusion). VEGF and sICAM-1 levels were measured by enzyme-linked immunoabsorbent assay. Before vitreous sampling, perifoveal capillary blood flow velocity was measured by fluorescein angiography with a scanning laser ophthalmoscope and the tracing method. The relations between perifoveal capillary blood flow velocity and the vitreous levels of VEGF and sICAM-1 were investigated. There was a significant correlation between perifoveal capillary blood flow velocity and the vitreous level of sICAM-1 (rho = -0.7303, p = 0.03). In contrast, there was no significant association between blood flow velocity and the vitreous level of VEGF (rho = -0.1458, p = 0.67). The vitreous level of sICAM-1 is associated with perifoveal capillary blood flow velocity in patients who have retinal vein occlusion and macular edema.

Effects of marine n-3 fatty acids on circulating levels of soluble adhesion molecules in patients with chronic heart failure.

Inflammatory markers as circulating soluble cellular adhesion molecules (sCAMs) and high sensitive C-reactive protein (hsCRP) are elevated in patients with chronic heart failure (CHF), and may constitute an increased risk of adverse outcome. Marine n-3 polyunsaturated fatty acids ( n-3 PUFA) may have anti-inflammatory effect and reduce levels of sCAMs (soluble intercellular adhesion molecule-1 (sICAM-1), vascular adhesion molecule-1 (sVCAM-1), P-selectin) and hsCRP. In a randomized, controlled trial, 138 patients with NYHA class II-III CHF were allocated to receive a daily supplement of 0.9 g of n-3 PUFA or olive oil for 24 weeks. After supplementation, no significant changes occurred in sCAMs or hsCRP after adjusting for possible confounders. However, a significant reduction was observed in sP-selectin in patients receiving n-3 PUFA, but this result was only of borderline significance in a between-group analysis. In conclusion, a daily supplement with 0.9 g of n-3 PUFA does not significantly affect plasma levels of sCAMs or hs-CRP in patients with CHF. n-3 PUFA may reduce sP-selectin, indicating a possible effect on platelet (and endothelial) activation. The results also indicate that the low dose of n-3 PUFA used in many intervention trials does not have deleterious effects on sCAMs or hsCRP.

CNS Elevation of Vascular and Not Mucosal Addressin Cell Adhesion Molecules in Patients with Multiple Sclerosis

The mucosal addressin cell adhesion molecule (MAdCAM) and vascular cell adhesion molecule (VCAM) appear to play roles in the recruitment of leukocytes to specialized endothelium lining the gastrointestinal tract. The purpose of this study was to clarify the role of MAdCAM and VCAM in the central nervous system by comparing protein expression in patients with multiple sclerosis (MS) and control subjects by immunohistochemistry. Specific antibodies to human VCAM and MAdCAM were used to confirm expression in control and MS nervous system specimens by immunohistochemistry. VCAM immunoreactivity was detected in endothelial cells, perivascular tissue, and in some cases, leukocytes within the meninges, gray, and white matter, of both controls and MS patients. VCAM immunoreactivity was maximal in a patient with acute active plaques, but of lower intensity and reduced distribution in controls and those with chronic active or inactive MS plaques. In contrast, MAdCAM immunoreactivity could not be detected in brain tissue from unaffected or MS patients. Taken together, these data support a role of VCAM, but not MAdCAM in the development of MS.

The Influence of Obesity and Different Fat Depots on Adipose Tissue Gene Expression and Protein Levels of Cell Adhesion Molecules

Increased circulating adhesion molecules in patients with obesity play an important role in the development of endothelial dysfunction/atherosclerosis. The aim of this study was to assess the contribution of various fat depots to the production of adhesion molecules in obesity. 12 women with first and second degree of obesity, 13 women with third degree of obesity and 14 lean age-matched women were included into study. Circulating levels of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and E-selectin were measured by Luminex kits. mRNA expression of ICAM-1, VCAM-1, E-selectin, monocyte chemoattractant protein-1 (MCP-1), and CD68 in subcutaneous (SAT) and visceral adipose tissue (VAT) was measured by RT-PCR; ICAM-1 and VCAM-1 protein levels by Luminex kits, normalized to protein content. Obesity increased ICAM-1 and VCAM-1 mRNA expression and protein levels and CD68 mRNA expression in VAT. Expression of E-selectin and MCP-1 did not significantly differ between groups. Expression of ICAM-1 and VCAM-1 positively correlated with expression of CD68 in both adipose depots. In VAT, ICAM-1 and VCAM-1 expression and protein levels positively correlated with BMI. Obesity was associated with increased adhesion molecules mRNA expression and protein levels in VAT, but not in SAT. Increased adhesion molecules production in visceral fat may provide a novel direct link between visceral adiposity and increased risk of cardiovascular complications.

Decreased Serum Fetuin-A Levels are Associated with Coronary Artery Diseases

To analyze Fetuin-A levels and soluble cellular adhesion molecules in patients with acute coronary syndrome. Serum Fetuin-A and intercellular adhesion molecule-1 (sICAM-1), vascular cellular adhesion molecule-1 (sVCAM-1) levels were examined in 127 patients who presented with chest pain. These patients were classified in three groups: stable angina (SA, n=51), myocardial infarction (MI, n=34) and non-cardiac group (n=42). Logarithmic transformations were made for Fetuin-A levels. Log-Fetuin-A levels were higher in non-cardiac subjects compared to MI and SA patients (p<0.05). Patients with SA showed lower levels than controls but higher levels as compared to MI patients. After controlling for age and gender, levels of sVCAM-1 and sICAM-1 in patients with coronary atherosclerosis were not different from those in non-cardiac subjects. Serum levels of soluble VCAM-1, ICAM-1 were not related to coronary artery disease (CAD), but fetuin-A levels seems to be decreased in SA and MI patients. Low fetuin-A may play a role in the pathophysiology of CAD.

Comparative Analysis of the Expression of Cell Adhesion Molecules in Cutaneous T-Cell Lymphomas (Mycosis Fungoides/Sézary Syndrome) and Inflammatory Skin Diseases

Introduction Cell adhesion molecules play a pivotal role in the establishment of T-cell populations in the skin. In this study, we quantify the expression of cell adhesion molecules in patients with cutaneous T-cell lymphoma (CTCL) and compare it with the expression found in other skin diseases. Material and methods Frozen material was obtained from 42 patients in 5 different groups: early CTCL, comprising patients with patch- and plaque-stage mycosis fungoides (n=11); advanced CTCL (n=7), comprising patients with mycosis fungoides (n=3) and Sézary syndrome (n=4); inflammatory skin disease (n=12), comprising patients with psoriasis (n=9) and atopic dermatitis (n=3); chronic skin diseases with persistent plaques that do not fulfil the histological criteria for mycosis fungoides (pre-CTCL) (n=8); and healthy volunteers (n=4). Expression of the following cell adhesion molecules was analyzed: lymphocyte function-associated antigen 1, intercellular adhesion molecule 1 (ICAM-1), ICAM-3, cutaneous lymphocyte-associated antigen, E-selectin, very late antigen 4, vascular cell adhesion molecule 1, αEβ7 integrin, and E-cadherin. Results The immunohistochemical analyses used here revealed statistically significant differences between CTCL and other skin diseases but not between early and advanced CTCL. The expression of αEβ7 integrin and ICAM-3 in the epidermis per high-power field (400× magnification) allowed the different groups to be distinguished from each other, except for advanced CTCL and pre-CTCL. There were statistically significant differences between advanced CTCL and pre-CTCL in terms of the expression of E-selectin at 400× magnification and the expression of ICAM-1 in a honeycomb pattern in epidermal keratinocytes. Conclusions The expression of cell adhesion molecules involved in the adhesion and migration of lymphocytes in the skin does not differ significantly between initial and advanced stages of CTCL.

The Effect of Iron Treatment on Adhesion Molecules in Patients with Iron Deficiency Anemia

The present study was aimed to determine the effect of iron supplementation on levels of soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) in patients with iron deficiency anemia (IDA). In this study, 26 female patients diagnosed with iron deficiency were treated approximately 3months of oral iron supplementation (99 ± 10days; ferrous glycine sulfate; 100mg/day of elemental iron). Levels of sICAM-1 and sVCAM-1 were assessed prior to treatment and after approximately 3months of treatment and compared with 26 healthy female subjects. A significant increase in sVCAM levels was found in the patients with iron deficiency at the end of the treatment relative to pretreatment levels compared to controls, whereas no significant differences were determined in sICAM levels. In the posttreatment period, no significant change was observed in sICAM levels compared to the pretreatment levels, whereas sVCAM levels decreased. However, after the treatment period, the sVCAM, hemoglobin, mean corpuscular volume (MCV), and serum ferritin levels did not return to the normal range compared to the controls. Pretreatment sVCAM-1 levels were inversely correlated with levels of hemoglobin, hemotocrit, MCV, serum iron, and ferritin. After treatment, the sVCAM-1 levels were negatively correlated with ferritin levels. Levels of sVCAM were significantly higher in patients with IDA than controls. After the treatment period, the sVCAM levels were not completely normalized in patients with IDA compared to controls, regardless of the presence of inadequate levels of hemoglobin, MCV, and serum ferritin. Thus, iron supplementation not only ameliorates anemia, but may also reduce the inflammation markers in cases with IDA.

ADAM10 Is the Constitutive Functional Sheddase of CD44 in Human Melanoma Cells

CD44 proteins are cell surface receptors for hyaluronic acid (HA), a component of the extracellular matrix that has multiple effects on cell behavior. CD44 can be shed from the cell surface by proteolytic cleavage. The resulting soluble form can interfere with the interaction between HA and membrane-bound CD44. Soluble CD44 can abolish the cell proliferation-promoting effect of HA on melanoma cell lines, suggesting that a better understanding of the shedding process might identify ways of blocking tumor cell proliferation. ADAM10, ADAM17, and MMP14 have previously been implicated in the shedding of CD44 from various tumor cells. Using immunohistochemistry we demonstrate that ADAM10 and ADAM17 but not MMP14 are significantly expressed on melanoma cells in histological sections. In human melanoma cell lines expression of these proteases could be blocked by transfection with appropriate siRNAs. However, only blocking of ADAM10 expression led to decreased shedding of CD44. In parallel, cell proliferation was promoted. Confocal microscopy demonstrated that ADAM10 and CD44 colocalize on the cell surface. We conclude that ADAM10 is the predominant protease involved in the constitutive shedding of endogenous CD44 from melanoma cells, and that enhancement of ADAM10 activity could be an approach to decrease the proliferation of melanoma cells.

Enhanced mobilization of CD34+ progenitor cells expressing cell adhesion molecules in patients with STEMI

Adult stem cells can contribute to myocardial regeneration after ischemic injury. The aim of the study was to determine (1) the amount of mobilized CD34(+)/CD117(+), CD34(+)/KDR(+) cells into peripheral blood (PB) in relation to inflammatory and haematopoietic cytokines, (2) the presence of circulating CD34(+) cells, expressing cell adhesion molecules (CAM), in patients with ST-segment elevation myocardial infarction (STEMI) in comparison to patients with coronary artery disease (CAD). Twenty-three patients with STEMI (<12 h), 24 patients with CAD and 15 control subjects were enrolled in this study. The patients were matched in age, 2-CAD, ejection fraction (45%) and end-diastolic volume index (70 ml/m(2)). The number of stem cells and the expression of adhesion molecules were quantified by use of flow cytometry. Inflammatory cytokines [interleukin-6 (IL-6), granulocyte colony-stimulating factor (G-CSF), vascular endothelial growth factor] and chemotactic factors as stromal cell-derived factor-1 (SDF-1), hepatocyte growth factor (HGF) were determined by ELISA. The amount of circulating progenitor cells including CD34(+)/CD117(+) and CD34(+)/KDR(+) cells was significantly higher in patients with STEMI than in patients with CAD (CD34(+)/CD117(+) 433 +/- 128 vs. 100 +/- 17, P = 0.012; CD34(+)/KDR(+) 253 +/- 41 vs. 128 +/- 24, P = 0.02). The mobilization of CD34(+) progenitor cells expressing CXCR4-receptor, lymphocyte function-associated antigen-1 (LFA-1), very late antigen-4 (VLA-4) and ICAM-1 into PB was significantly higher in patients with STEMI compared to CAD (CD34(+)/CXCR4(+) 740 +/- 327 vs. 136 +/- 23, P = 0.006; CD34(+)/LFA-1 976 +/- 227 vs. 329 +/- 41, P = 0.025; CD34(+)/VLA4(+) 830 +/- 161 vs. 330 +/- 31, P = 0.007; CD34(+)/ICAM(+) 387 +/- 66 vs. 144 +/- 26, P < 0.001). Additionally, the cytokines G-CFS, IL-6 and HGF were upregulated and significantly increase in the STEMI group compared with controls and CAD (G-CSF 50.6 +/- 6.8 vs. 23 +/- 3 vs. 23.8 +/- 2, P (Co vs. STEMI) < 0.001, P (Co vs. CAD) = n.s., P (STEMI vs. CAD) < 0.001; IL-6 8.4 +/- 0.6 vs. 3.8 +/- 1.9 vs. 2.6 +/- 1, P (Co vs. STEMI) < 0.001, P (Co vs. CAD) = n.s., P (STEMI vs. CAD) < 0.001; HGF 4,502 +/- 461 vs. 686 +/- 195 vs. 1,746 +/- 461, P (Co vs. STEMI) < 0.001, P (Co vs. CAD) = n.s., P (STEMI vs. CAD) < 0.001), while the level of SDF-1 was increased in patients with CAD compared to controls and patients with STEMI (3,035 +/- 286 vs. 2,028 +/- 76 vs. 2,154 +/- 234, P (Co vs. STEMI) = n.s., P (Co vs. CAD) = n.s., P (STEMI vs. CAD) = 0.005). The study demonstrates in patients with STEMI an increased mobilization of progenitor cells like CD34(+)/CD117(+) and CD34(+)/KDR(+) compared to CAD. Furthermore, we could shown that in patients with STEMI the mobilization of CD34(+) progenitor cells with expressed CAM was increased. It is to speculate that an enhanced expression of adhesion molecules may increase the transmigration and implantation of progenitor cells into ischemic myocardium for myocardial repair.

Circulating adhesion molecules in patients with Keshan disease and their relationship with Coxsackie B virus infection

This study determined the levels of serum soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecular-1 (sVCAM-1) in patients with different types of Keshan disease (KD), examined the relationship between Coxsackie B virus-specific IgM antibody (CBV-IgM) and sICAM-1 or sVCAM-1 in KD patients, and investigated the role of these adhesion molecules in the pathogenesis of KD and their clinical implications. The levels of serum sICAM-1, sVCAM-1 and CBV-IgM were measured by using enzyme-linked immunosorbent assay in 22 patients with chronic Keshan disease (CKD), 27 with latent Keshan disease (LKD) and 28 healthy controls. The subjects in different groups were adjusted for sex and age. Echocardiography was adopted to determine left ventricular ejection fraction (LVEF) in 22 patients with CKD. The results showed that CKD patients had significantly higher levels of sICAM-1 and sVCAM-1 than LKD patients and healthy controls (P<0.01 for all). And there was significant difference in the levels of the 2 adhesion molecules between LKD patients and healthy controls (P<0.05). A negative correlation was found between LVEF and sICAM-1 or sVCAM-1 in CKD patients. The percentage of CBV-specific IgM positive individuals in KD patients was significantly higher than that of healthy controls. In CVB-specific IgM positive patients, the levels of serum sICAM-1 and sVCAM-1 were significantly greater than those in CBV-specific IgM negative counterpart. It was concluded that the increase in the levels of sICAM-1 and sVCAM-1 suggests the progression of inflammation in KD. sICAM-1 and sVCAM-1 can promote the development of myocardial pathology and lead to poor myocardial function. The increased serum sICAM-1 and sVCAM-1 in KD patients may be related to CBV infection.

RETRACTED ARTICLE: Evaluation of renal vascular lesions using thrombomodulin and vascular cell adhesion molecule-1 in patients with biopsy-proven lupus nephritis.

The authors discovered post-publication that the data submitted was incorrect. According to the study data, the patients were all IV lupus nephritis patients. However, on further review, the authors found that some patients in the study were not IV lupus nephritis, which meant that the diagnosis was wrong and the clinical data and the levels of thrombomodulin and vascular cell adhesion molecule-1 were not correctly reported. The authors apologize for this error, and have requested the manuscript to be withdrawn. Clin Rheumatol DOI 10.1007/s10067-009-1167-2

Soluble Endoglin and Its Interaction with Adhesion Molecules in Patients with Thalassemia Intermedia

Endoglin (CD105) is an accessory protein of the transforming growth factor-β receptor system expressed on vascular endothelial cells. Mutations on the endoglin gene are associated with hereditary hemorrhagic telangiectasias (Osler-Weber-Rendu syndrome) and, thus, endoglin has been extensively studied in the context of this disease. Endoglin is highly expressed on endothelial cells in healing wounds, developing embryos, inflammatory tissues and solid tumors. It is a marker of activated endothelium, while its vascular expression is limited to proliferating cells. Previous studies have shown that the endothelial function is impaired in patients with Thalassemia Intermedia (TI). Oxidative damage resulting from hemolysis and iron load, leads to increased expression of the intercellular and vascular adhesion molecules-1 (ICAM-1 and VCAM-1) and impaired nitric oxide (NO) bioavailability. As endoglin plays a critical role in angiogenesis and dysregulation of its expression and/or activity has been implicated in multiple vascular diseases, we aimed to investigate the expression of endoglin and its correlation with factors of endothelial dysfunction in patients with TI. Thirty adult patients with TI were included in the study, while 20 healthy individuals served as controls. Soluble endoglin, soluble forms of adhesion molecules ICAM-1, VCAM-1, E and P-Selectins, thrombomodulin, von Willebrand factor, as well as NO and vascular endothelial growth factor (VEGF), were measured in patients and controls, by immunoenzymatic methods. The main results of the study are:levels of endoglin, E-selectin, thrombomodulin, VCAM-1, ICAM-1 and VEGF in patients with TI (5.5±0.4 ng/ml, 91.4±20.0 ng/ml, 48.8±16.5 ng/ml, 1413.7±176.1 ng/ml, 658.8±34.6 ng/ml and 619.1±227.8 pg/ml, respectively) were higher compared to controls (4.9±0.3 ng/ml, 10.3±2.2 ng/ml, 4.0±0.6 ng/ml, 328.3±43.8 ng/ml, 107.6±26.5 ng/ml, 81.3±58.1 pg/ml), (p<0.01),endoglin levels in patients with TI correlated positively with concentrations of ICAM-1 (r=0.760, p<0.003), VCAM-1 (r=0.520, p<0.05), E-Selectin (r=0.790, p<0.0020, P-Selectin (r=0.530, p<0.04), while these correlations were absent in normal individuals.Angiogenesis is a highly coordinated process in which VEGF, endoglin and hypoxia inducible factor 1 (HIF-1) play a pivotal role by coordinating interaction between endothelial cells, extracellular matrix and the surrounding cells. Taking into assumption that endoglin is a protective-repair tissue protein, our findings support the hypothesis that patients with TI exhibit increased degree of angiogenesis and endothelial regeneration, which are probably compensatory mechanisms in response to tissue hypoxia and damage.