Plasma Levels Of Intercellular Adhesion Molecule-1 Research Articles

0053 Effect of Changes in Intracellular Adhesion Molecule-1 on Measures of Sleepiness and 24-hour Ambulatory Blood Pressure After 4 Months of Continuous Positive Airway Pressure

Abstract Introduction Previous studies have shown that continuous positive airway pressure (CPAP) therapy of adults with obstructive sleep apnea (OSA) reduces circulating levels of intercellular adhesion molecule 1 (ICAM-1). ICAM-1 levels may affect daytime sleepiness and elevated blood pressure associated with OSA. Our goals were to explore associations between changes in ICAM-1 and objective and subjective measures of sleepiness, as well as 24-hour ambulatory blood pressure monitor (ABPM) parameters in adults with OSA following 4 months of CPAP treatment. Methods We identified 140 adults with newly diagnosed OSA in the Penn Icelandic Sleep Apnea (PISA) Study, with a mean (±SD) body mass index (BMI) of 31.5±4.2 kg/m2 and apnea-hypopnea index (AHI) of 36.8±15.3 events/hour; 83.3% were males. Plasma ICAM-1 levels, 24-hour ABPM, Epworth Sleepiness Scale (ESS), and Psychomotor Vigilance Task (PVT) measures were obtained at baseline and after 4 months of CPAP treatment. Associations between changes in natural log ICAM-1 and both sleepiness and 24-hour mean arterial blood pressure (MAP) were assessed using multivariate regression models, controlling for a priori baseline covariates of age, sex, BMI, race, site, smoking status, physical activity, use of anti-hypertensive medications, AHI and hours/night of CPAP usage. Results Overall, there was no significant change in ICAM-1 from baseline to follow-up among all participants after 4 months (0.027 ng/ml, p=0.52). There were no statistically significant associations between the change in ICAM-1 and change in sleepiness measures (all p>0.05) or 24-hour MAP (1.124 mm Hg, p=0.07). A nominal association between increased ICAM-1 and increased daytime MAP after 4 months was observed (1.39 mm Hg, p=0.033), although this result was not significant after correction for multiple comparisons. Conclusion Our results do not support changes in ICAM-1 as the biological pathway linking changes in sleepiness or ABPM following CPAP treatment of adults with OSA. Support P01-HL094307 (NHLBI, PI: Pack AI)

PM2.5-induced oxidative stress increases intercellular adhesion molecule-1 expression in lung epithelial cells through the IL-6/AKT/STAT3/NF-\u03baB-dependent pathway

BackgroundEpidemiological studies have shown that ambient air pollution is closely associated with increased respiratory inflammation and decreased lung function. Particulate matters (PMs) are major components of air pollution that damages lung cells. However, the mechanisms remain to be elucidated. This study examines the effects of PMs on intercellular adhesion molecule-1 (ICAM-1) expression and the related mechanisms in vitro and in vivo.ResultThe cytotoxicity, reactive oxygen species (ROS) generation, and monocyte adherence to A549 cells were more severely affected by treatment with O-PMs (organic solvent-extractable fraction of SRM1649b) than with W-PMs (water-soluble fraction of SRM1649b). We observed a significant increase in ICAM-1 expression by O-PMs, but not W-PMs. O-PMs also induced the phosphorylation of AKT, p65, and STAT3. Pretreating A549 cells with N-acetyl cysteine (NAC), an antioxidant, attenuated O-PMs-induced ROS generation, the phosphorylation of the mentioned kinases, and the expression of ICAM-1. Furthermore, an AKT inhibitor (LY294002), NF-κB inhibitor (BAY11–7082), and STAT3 inhibitor (Stattic) significantly down-regulated O-PMs-induced ICAM-1 expression as well as the adhesion of U937 cells to epithelial cells. Interleukin-6 (IL-6) was the most significantly changed cytokine in O-PMs-treated A549 cells according to the analysis of the cytokine antibody array. The IL-6 receptor inhibitor tocilizumab (TCZ) and small interfering RNA for IL-6 significantly reduced ICAM-1 secretion and expression as well as the reduction of the AKT, p65, and STAT3 phosphorylation in O-PMs-treated A549 cells. In addition, the intratracheal instillation of PMs significantly increased the levels of the ICAM-1 and IL-6 in lung tissues and plasma in WT mice, but not in IL-6 knockout mice. Pre-administration of NAC attenuated those PMs-induced adverse effects in WT mice. Furthermore, patients with chronic obstructive pulmonary disease (COPD) had higher plasma levels of ICAM-1 and IL-6 compared to healthy subjects.ConclusionThese results suggest that PMs increase ICAM-1 expression in pulmonary epithelial cells in vitro and in vivo through the IL-6/AKT/STAT3/NF-κB signaling pathway.

Association between Vascular Endothelial Markers and Carotid Intima-Media Thickness in Children and Adolescents with Type 1 Diabetes Mellitus.

Type 1 Diabetes Mellitus (T1DM) is one of the important risk factor for cardiovascular disease. Endothelial dysfunction and increased Carotid Intima-Media Thickness (CIMT) result in cardiovascular complications. Vascular Cell Adhesion Molecule-1 (VCAM-1) and Intercellular Adhesion Molecule-1 (ICAM-1) are two adhesion molecules that are markers of early atherosclerosis and play a significant role in developing atherosclerosis. To evaluate CIMT and its association with the levels of ICAM-1 and VCAM-1 in children and adolescents with T1DM. In this descriptive, cross-sectional study conducted between April 2013 and September 2014, 29 children aged 7-20 years with T1DM for at least two years and 29 age and sex-matched, healthy individuals were evaluated. Plasma level of ICAM-1 and VCAM-1 was measured by ELISA, and CIMT via Doppler ultrasound was also assessed. The data were analysed by t-test and Pearson's correlation coefficient in SPSS 16.0 (p≤0.05). Independent t-test indicated that there is a significant difference in ICAM-1 level between the patients and controls (p<0.001). Further, CIMT was significantly higher in diabetic subject (p<0.001). CIMT was not significantly associated with the level of VCAM-1 and ICAM-1 in the patients (p>0.5). ICAM-1 and VCAM-1 were not associated with CIMT but, CIMT and level of ICAM-1 were significantly, higher in diabetic patients, and therefore could be used as useful tools for identification of early atherosclerosis in children and adolescents with T1DM.

P16 INTERCELLULAR ADHESION MOLECULE-1 K469E(A/G) POLYMORPHISM AND ITS EFFECTS IN THE DEVELOPMENT OF DIABETIC NEPHROPATHY

Recent research has implicated that inflammation may be a key pathophysiological mechanism in diabetic nephropathy (DN), although its pathogenesis is multifactorial. Intercellular adhesion molecule 1 (ICAM-1) is an acute phase marker of inflammation and the ICAM-1 gene is located on chromosome 19p13.2 and resides a linkage region to diabetes and DN. To investigate whether ICAM-1 has effects in the development of DN, we have recently performed genetic and pathological studies of this molecule in Swedish and Malaysian subjects with normal glucose tolerance (NGT), diabetes and DN. We genotyped six single nucleotide polymorphisms (SNPs) in the ICAM-1 gene with TaqMan allelic discrimination. We also determined plasma ICAM-1 levels with an enzyme-linked immune-sorbent assay kit. We found that non-synonymous SNP rs5498 (K469E A/G) was associated diabetes and DN and the G allele had a protective effect. Particularly, we found a high heterozygous index of this polymorphism presenting in both populations. The genotype distribution of this polymorphism was kept in Hardy-Weinberg Equilibrium and no duplicon in the genomic sequence was found. The ICAM-1 K469E(A/G) polymorphism resides in the 5th Ig-like domain of ICAM-1 protein. This domain is essential for dimerization, surface presentation and solubilisation of proteins of the protein and subsequently plays a crucial role in the activity of ICAM-1 protein in the interaction with LFA-1 and the adhesion of B cells. Furthermore, we found the carriers with heterozygous genotype had higher fasting glucose levels among newly diagnosed type 2 diabetes patients compared with the subjects with wild or mutant homozygous genotype. Plasma ICAM-1 levels were increased from the subjects with NGT, diabetes without DN to the patients with DN. Among diabetic patients with DN, the carriers with heterozygous genotype had higher plasma ICAM-1 levels compared with other patients. Our study provided evidence that ICAM-1 has effects in the development of DN. The patients carrying with heterozygous genotype of SNP rs5498 (K469E A/G) in the ICAM-1 gene have higher risk susceptibility to DN. The combined approach with genotyping this polymorphism and measuring plasma ICAM-1 levels may be useful for prediction of DN in translation medicine.

Genetic, epigenetic and protein analyses of intercellular adhesion molecule 1 in Malaysian subjects with type 2 diabetes and diabetic nephropathy

AimsRecent research has implicated that the inflammation may be a key pathophysiological mechanism in diabetic nephropathy (DN). Intercellular adhesion molecule 1 (ICAM-1) is an acute phase marker of inflammation. In the present study, we carried out genetic, epigenetic and protein analyses of ICAM-1 in a Malaysian population, including normal glucose tolerance (NGT) subjects and type 2 diabetes (T2D) patients with or without DN in order to evaluate its role in DN. MethodsAnalyses of DNA polymorphism and methylation in the ICAM1 gene were performed with TaqMan allelic discrimination and pyrosequencing, respectively. Plasma ICAM-1 levels were determined using an enzyme-linked immune-sorbent assay kit. ResultsWe found that the ICAM1 K469E(A/G) polymorphism (rs5498) was significantly associated with DN. Particularly, 86.1% of T2D patients with DN carried heterozygous genotype compared to the patients without DN (68.6%). Furthermore, plasma ICAM-1 levels were increased from NGT subjects to T2D patients without and with DN (P<0.001). The NGT subjects carrying heterozygous genotype had significantly lower plasma ICAM-1 levels compared to the K469(A/A) genotype carriers (P=0.009). In the ICAM1 gene promoter, DNA methylation levels of CpG sites were low, and no association of the ICAM1 DNA methylation alteration with DN was detected. ConclusionThe present study provided evidence that the ICAM1 K469E(A/G) polymorphism with high heterozygous index and elevation of plasma ICAM-1 levels were associated with DN in a Malaysian population. Further prospective study of ICAM-1 protein according to the ICAM1 K469E(A/G) genotypes is necessary for predicting the susceptibility to T2D and DN.

Elevation of soluble intercellular adhesion molecule-1 levels, but not angiopoietin 2, in the plasma of human immunodeficiency virus-infected African women with clinical Kaposi sarcoma.

Circulating levels of endothelial activation biomarkers are elevated in during infection with human immunodeficiency virus 1 (HIV-1) and may also be increased in Kaposi sarcoma (KS). We compared 23 HIV-1-seropositive women with clinically diagnosed KS with 46 randomly selected controls matched for visit year, CD4 count, and antiretroviral therapy status. Conditional logistic regression was used to identify differences between cases and controls. The odds of clinical KS increased with increasing plasma viral load and with intercellular adhesion molecule 1 (ICAM-1) levels above or equal to the median. There was a borderline association between increasing plasma angiopoietin 2 levels and KS. In multivariable modeling including plasma viral load, angiopoietin 2, and ICAM-1, plasma ICAM-1 levels above or equal to the median remained associated with clinical KS (odds ratio = 14.2, 95% confidence interval = 2.3-87.7). Circulating ICAM-1 levels should be evaluated as a potential biomarker for disease progression and treatment response among HIV-infected KS patients.

Effects of Dexamethasone on Intercellular Adhesion Molecule 1 Expression and Inflammatory Response in Necrotizing Acute Pancreatitis in Rats

Adhesion molecules are involved in the inflammatory response during acute pancreatitis (AP). We investigated the effect of dexamethasone (Dx) on intercellular adhesion molecule 1 (ICAM-1) expression during AP and its consequences on leukocyte recruitment and pancreatic damage. Acute pancreatitis was induced in rats by 3.5% sodium taurocholate for 3 hours and 6 hours. Dexamethasone (1 mg/kg) was administered either 30 minutes before or 1 hour after inducing AP. Messenger RNA ICAM-1 expression in pancreas and lung, membrane-bound ICAM-1 in acinar cells, and ICAM-1 plasma levels were analyzed. Histological examination of the pancreas and neutrophil infiltration in pancreas and lung were also measured. Prophylactic and therapeutic administration of Dx down-regulated ICAM-1 expression in pancreas and lung from early AP. Dexamethasone given before AP reduced the pancreatic damage, but lung inflammation was not prevented. Therapeutic Dx treatment was ineffective in avoiding leukocyte recruitment into the pancreas and lung in rats with AP. High ICAM-1 concentration was found in plasma during AP, which was not reduced by Dx treatments. Dexamethasone down-regulates ICAM-1 expression, but it does not completely prevent leukocyte recruitment during sodium taurocholate-induced AP.

Effect of Atorvastatin on Haemostasis, Fibrinolysis and Inflammation in Normocholesterolaemic Patients with Coronary Artery Disease

Treatment with HMG-CoA reductase inhibitors (statins) reduces the morbidity and mortality of coronary artery disease (CAD). In addition to their lipid-lowering actions, pleiotropic effects of statins have been demonstrated. The aim of the present study was to assess if atorvastatin therapy has an impact on haemostasis, fibrinolysis and inflammation in normocholesterolaemic patients with CAD. Fifty-four patients with CAD who had received atorvastatin treatment for at least 8 weeks (mean dosage 30 mg/day) and 54 patients with CAD who had not received atorvastatin therapy were selected from a larger prospective, randomized, double-blind study for inclusion in this post hoc analysis. Patients were matched by their total cholesterol levels. All patients were normocholesterolaemic. In the atorvastatin-treated patients significantly lower plasma levels of thrombin-antithrombin complexes (p < 0.05), plasminogen activator inhibitor-1 activity (PAI-1) [p < 0.05], soluble vascular cell adhesion molecule-1 (p < 0.05), soluble platelet selectin (p < 0.05) and high-sensitivity C-reactive protein (p < 0.05) were measured compared with patients not on atorvastatin therapy. Additionally, a strong trend towards lower soluble intercellular adhesion molecule-1 plasma levels was detected in patients treated with atorvastatin. No differences were found in tissue-type plasminogen activator antigen, plasmin-plasmin inhibitor complexes, fibrinogen, D-dimer and activated factor XII values. Atorvastatin appears to have an effect on coagulation activation, fibrinolysis and inflammation in patients with CAD. Reduction in PAI-1 and reduced thrombin formation may have an impact on cardiovascular morbidity and mortality in patients with CAD.

9054 Histology classification is not a predictor of clinical outcomes in advanced non-small cell lung cancer (NSCLC) treated with vinorelbine or gemcitabine combinations

Recent research has implicated that the inflammation may be a key pathophysiological mechanism in diabetic nephropathy (DN). Intercellular adhesion molecule 1 (ICAM-1) is an acute phase marker of inflammation. In the present study, we carried out genetic, epigenetic and protein analyses of ICAM-1 in a Malaysian population, including normal glucose tolerance (NGT) subjects and type 2 diabetes (T2D) patients with or without DN in order to evaluate its role in DN.Analyses of DNA polymorphism and methylation in the ICAM1 gene were performed with TaqMan allelic discrimination and pyrosequencing, respectively. Plasma ICAM-1 levels were determined using an enzyme-linked immune-sorbent assay kit.We found that the ICAM1 K469E(A/G) polymorphism (rs5498) was significantly associated with DN. Particularly, 86.1% of T2D patients with DN carried heterozygous genotype compared to the patients without DN (68.6%). Furthermore, plasma ICAM-1 levels were increased from NGT subjects to T2D patients without and with DN (P < 0.001). The NGT subjects carrying heterozygous genotype had significantly lower plasma ICAM-1 levels compared to the K469(A/A) genotype carriers (P = 0.009). In the ICAM1 gene promoter, DNA methylation levels of CpG sites were low, and no association of the ICAM1 DNA methylation alteration with DN was detected.The present study provided evidence that the ICAM1 K469E(A/G) polymorphism with high heterozygous index and elevation of plasma ICAM-1 levels were associated with DN in a Malaysian population. Further prospective study of ICAM-1 protein according to the ICAM1 K469E(A/G) genotypes is necessary for predicting the susceptibility to T2D and DN.

Lower bone mineral density in children with type 1 diabetes is associated with poor glycemic control and higher serum ICAM-1 and urinary isoprostane levels

The purpose of the study was to investigate bone mineral density (BMD) in children with type 1 diabetes (DM1) and to establish the relationships between BMD, physical activity, glycemic control, and markers of systemic oxidative stress and inflammation. We studied 30 children with DM1, aged 4.7-18.6 years, and 30 healthy subjects, matched by sex, age, and body mass index (BMI). Mean duration of DM1 was 5.4 +/- 3.4 years and mean glycosylated hemoglobin (HbA(1c)) level over 12 months was 9.8 +/- 1.5%. Lumbar and total bone mineral density (BMD, g/cm(2)) were measured by dual-energy X-ray absorptiometry (DXA). We calculated the apparent volumetric lumbar BMD (BMDvol, g/cm(3)) and total mineral content adjusted for age and height (BMCadj), and measured plasma intercellular adhesion molecule-1 (ICAM-1), high sensitivity C-reactive protein (hs-CRP), and urinary 8-iso-prostaglandin F(2a) (F(2)-IsoPs). Calcium (Ca) intake was assessed by questionnaire and physical activity by questionnaire and accelerometer (ActiGraph, count/h). Total BMCadj and lumbar BMDvol were significantly lower in children with DM1 than in controls (101.8 +/- 7.7 vs. 107 +/- 5.7%, P = 0.005; 0.32 +/- 0.08 vs. 0.36 +/- 0.09 g/cm(3), P = 0.05, respectively). These differences were mostly caused by the differences in boys. Plasma ICAM-1 and hs-CRP levels were significantly higher in the DM1 group compared to the controls. Ca intake and urine F(2)-IsoPs levels were similar between the groups. Diabetic boys were less active than controls (18231 +/- 6613 vs. 24145 +/- 7449 count/h, P = 0.04). In the DM1 group, lumbar BMDvol correlated inversely with urinary F(2)-IsoPs (r = -0.5; P = 0.005) and plasma ICAM-1 levels (r = -0.4; P = 0.02), and also with HbA(1c) levels after adjustment for age (r = -0.45; P < 0.05). Total BMCadj correlated inversely with HbA(1c) levels (r = -0.4; P = 0.02). We conclude that children with DM1, particularly boys, have lower BMD. Poor glycemic control, elevated markers of oxidative stress, and inflammation are associated with lower BMD.

Plasma Levels of VCAM-1, ICAM-1, E-Selectin, and P-Selectin in 99 HIV-Positive Patients Versus 51 HIV-Negative Healthy Controls

Plasma Levels of VCAM-1, ICAM-1, E-Selectin, and P-Selectin in 99 HIV-Positive Patients Versus 51 HIV-Negative Healthy Controls

Air pollution and inflammation in type 2 diabetes: a mechanism for susceptibility

Background: Particulate air pollution has been associated with several adverse cardiovascular health outcomes, and people with diabetes may be especially vulnerable. One potential pathway is inflammation and endothelial dysfunction—processes in...

Dietary fish oil enhances adhesion molecule and interleukin-6 expression in mice with polymicrobial sepsis

This study investigated the effects of fish oil (FO) diet on plasma intercellular adhesion molecule 1 (ICAM-1) levels and leucocyte integrin expression in polymicrobial sepsis. Mice were randomly assigned to a control group and an FO group. The control group was fed a medium-fat diet containing soyabean oil, whereas in the FO group, 70 % of the soyabean oil was replaced by FO for 3 weeks. After that, sepsis was induced by caecal ligation and puncture (CLP) in the experimental groups and mice were killed at 0, 6, 12 and 24 h, respectively, after CLP. Results showed that compared with the control group, plasma ICAM-1 levels were higher in the FO group 6 h after CLP. Intra-lymphocyte interferon-gamma expression in the FO group was lower, whereas IL-4 expression was higher than in the control group 12 and 24 h after CLP. The expression of leucocyte integrin was significantly higher in the FO group 12 and 24 h after CLP. The FO group had higher IL-6 levels at 12 h in the lungs, at 6 and 12 h in the kidneys, and at 6, 12 and 24 h in the intestines after CLP. The survival rate did not differ between the two groups after CLP. The present findings suggest that pretreatment with an FO diet enhances adhesion molecule and inflammatory cytokine expressions during sepsis, which might aggravate the inflammatory reaction and increase neutrophil infiltration into tissues. In addition, FO diet promotes the Th2-type response and suppresses cellular immune response in polymicrobial sepsis.

Plasma Soluble Adhesion Molecule Levels in Coronary Artery Ectasia

Background:Coronary artery ectasia (CAE) is defined as localized or diffuse dilatation of the coronary arteries. There are scarce data about the role of inflammation in CAE. In the present study, the plasma soluble adhesion molecules intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) levels in CAE were investigated. Methods: The study population (n = 67) consisted of four groups. Group 1: patients with normal coronary artery (NCA); group 2: patients with isolated ectasia without stenotic lesion; group 3: patients with obstructive coronary artery disease (OCAD) without CAE; group 4: patients with both OCAD and CAE. Results: Plasma concentrations of ICAM-1 and VCAM-1 were higher in patients with isolated ectasia than in cases with NCA (p < 0.001 and p < 0.001, respectively). Compared with OCAD patients, patients with CAE had significantly elevated concentrations of ICAM-1 and VCAM-1 (p < 0.001 and p < 0.05, respectively). The levels of ICAM-1 and VCAM-1 of the CAE and OCAD group were higher than in patients in the OCAD group (p < 0.05 and p < 0.05, respectively). We detected a positive correlation between the presence of CAE and the levels of ICAM-1 and VCAM-1. Multivariate logistic regression analyses revealed a significant independent relation between the presence of CAE and ICAM-1 and VCAM-1. Conclusion: We found elevated plasma levels of ICAM-1 and VCAM-1 in patients with CAE and OCAD + CAE compared with subjects with NCA and OCAD. These data strongly suggest that more severe vascular wall inflammation may play a role in the pathogenesis of CAE.

Hemostatic activation in a chemically induced rat model of severe hemolysis and thrombosis

Introduction In hemolytic diseases such as sickle cell disease and β-thalassemia, the mechanisms of thrombosis are poorly understood, however erythrocyte/endothelium interactions are thought to play an important role. Appropriate animal models would increase our understanding of the pathophysiology of thrombosis and aid in the development of new therapeutic strategies. We previously reported that rats exposed to 2-butoxyethanol (2-BE) develop hemolysis and enhanced adherence of erythrocytes to the extracellular matrix, possibly secondary to the recruitment of cellular adhesion molecules at the erythrocyte/endothelium interface. Methods We exposed rats to 250 mg/kg/day of 2-BE for 4 days, and collected blood for coagulation markers on each day. Results As previously observed, erythrocytes dropped precipitously (8.0 to 1.8 × 10 6/μl in 48 h), and diffuse microvascular thrombosis developed in the heart, lungs, liver, bones and eyes. Prothrombin times, activated partial thromboplastin times, fibrinogen, and antithrombin-III were unchanged between treated and control rats, indicating that hemostasis is largely unperturbed. However the thrombin–antithrombin III levels in the 2-BE treated rats for all days were 3–7 times greater than the control rats. The plasma intercellular adhesion molecule-1 (ICAM-1) levels of 2-BE treated animals were approximately twice that of the controls on days 2 and 3 and 1.5 times the controls on day 4 ( P < 0.05). Conclusion Our findings are consistent with the observations of increased erythrocyte aggregation, increased erythrocyte/endothelium interaction, and increased plasma ICAM-1 levels observed in sickle cell disease and β-thalassemia patients. This model may be useful for studying therapeutic agents that disrupt erythrocyte/endothelium interactions.

Endothelium dysfunction markers in patients with diabetic retinopathy

Diabetes mellitus leads to endothelium dysfunction and an accelerated progression of atherosclerosis. Vascular complications of diabetes mellitus can affect not only large and medium arteries resulting in coronary heart disease and peripheral arteries diseases, but also small vessels leading to retinopathy and nephropathy. Intercellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1), E-selectin and von Willebrand factor (vWF) are considered as markers of endothelium dysfunction. The aim of our study was to evaluate plasma levels of ICAM-1, VCAM-1, E-selectin and vWF in patients with type 2 diabetes mellitus receiving insulin therapy and who had diabetic non-proliferative retinopathy, proliferative retinopathy, or did not develop diabetic retinopathy. There were no statistically significant differences between studied groups in any of evaluated endothelium dysfunction markers. There was no statistically significant correlation between measured parameters and a period of diabetic history. None of the studied markers presented a significant correlation with a period of insulin treatment.

Effect of adjuvant chemotherapy on circulating levels of ICAM, VCAM, VEGF and VEGFD in women with lymph node positive breast cancer.(NOGGO trial)

9602 Background: Intercellular adhesion molecule (ICAM), and vascular cell adhesion molecule (VCAM) play a role in cell adhesion to the vascular endothelium, and may have a role in tumour cell dissemination. Expression of Vascular Endothelial Growth Factor (VEGF) has been proposed as a prognostic indicator in breast cancer, because as one of the important factors involved in angiogenesis. Our aim of the present study was to investigate the effect of chemotherapy on plasma levels of ICAM, VCAM, VEGF und VEGFD in patients with breast cancer and to compare their levels among patients with different pathological features. Methods: Patients with resected breast cancer involving 1–3 axillary lymph nodes were treated in conventional 21d intervalls with ECT (Arm A): 4x epirubicin (90mg/m2, d1) /cyclophosphamide (600 mg/m2, d1) followed by 4x paclitaxel (175 mg/m2, d1). Arm B was treated with dose-dense ET in 14 days intervalls: 4x of epirubicin (120mg/m2, d1) followed by 4x paclitaxel (175 mg/m2, 3h, d1) with obligatory G-CSF support (5 mg/kg G-CSF d5–10). Blood samples of 83 patients (45 pat. Arm A, 38 pat. Arm B) were collected before chemotherapy (group BEFORE) and after administration of 8 cycle of adjuvant chemotherapy (group AFTER). Plasma levels of ICAM, VCAM, VEGF and VEGFD were measured with commercially available ELISA assays. Results: The plasma ICAM level before chemotherapy was significantly higher (p<0,017) in postmenopausal patients. The plasma VCAM level showed significant cross-correlation with VEGF (p<0,025) and VEGF-D levels (p<0,039) before chemotherapy. In addition, ICAM und VCAM levels after chemotherapy were significantly higher than ICAM (p<0,0001) and VCAM levels (p<0,001) before chemotherapy. Measured levels of VCAM after chemotherapy were significantly higher in ARM B with dose-intensification of ET. Conclusions: We conclude there are higher levels of adhesion molecules after chemotherapy and a cross-correlation to VEGF and VEGF-D. No significant financial relationships to disclose.

Changes in plasma levels of adhesion molecules after percutaneous mitral balloon valvuloplasty

Background Adhesion molecules are expressed on vascular endothelium and on immune and inflammatory cells. Recently increased levels of adhesion molecules have been shown in patients with rheumatic mitral stenosis. This study examined the serum levels of the adhesion molecules intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and E-selectin in patients with rheumatic mitral stenosis and the effects of percutaneous mitral balloon valvuloplasty (PMBV) on these adhesion molecules. Materials and methods Thirty five patients (3 men, 32 women, mean age 39±5 years) with severe rheumatic mitral stenosis who underwent percutaneous balloon mitral valvuloplasty, and 35 age and sex matched healthy control subjects were included in the study. Serum levels of ICAM-1, VCAM-1, and E-selectin were measured in all patients who underwent PMBV and in all control subjects. Blood samples were taken for measurement of adhesion molecules immediately before and 24 h after the mitral balloon valvuloplasty. Results The plasma levels of soluble adhesion molecules E-selectin, ICAM-1 and VCAM-1 were significantly elevated in patients with mitral stenosis compared to control subjects: E-selectin, 97±59 vs. 45±24 ng/ml ( P=.001), sICAM-1, 874±301 ng/ml vs. 238±82 ng/ml ( P<.0001); sVCAM-1, 3056±763 ng/ml vs. 985±298 ng/ml ( P<.0001). Plasma levels of VCAM-1 significantly increased 24 h after the valvuloplasty procedure (3056±763 ng/ml vs. 3570±1225 ng/ml P=.013). Plasma levels of E-selectin showed a significant decrease after PMBV (97±59 vs. 70±58 ng/ml, P=.043) and plasma levels of ICAM-1 did not show any change after PMBV (874±301 vs. 944±377 ng/ml, P=.356). Conclusion Cellular adhesion molecules, sICAM-1, E-selectin, sVCAM-1 have shown changes in different directions in response to PMBV. These results necessitate further studies to clarify the mechanism underlying the association between adhesion molecules and PMBV as well as rheumatic mitral stenosis.

Circulating soluble adhesion molecules ICAM-1 and VCAM-1 and incident coronary heart disease: The PRIME Study

The Epidemiological Study of Myocardial Infarction Study which enrolled 9758 apparently healthy men aged 50–59 years, is a prospective cohort study designed to evaluate markers of coronary risk. Soluble forms of the intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) levels were measured in plasma obtained at baseline from 317 subjects who suffered a coronary event during the 5-year follow-up and in twice the number of control subjects who were matched for center, age and day of inclusion in a nested case-control design. The relative risk associated with the highest compared with the lowest thirds of ICAM-1 (>625 versus <502 ng/ml) was 2.45 (95% CI: 1.64–3.65, P<0.001) without adjustment; it decreased moderately (RR: 2.09; 95% CI: 1.34–3.24, P<0.001) after control for lipid and non-lipid factors and remained significantly elevated after adjustment for C-reactive protein (CRP) (RR: 1.90; 95% CI: 1.21–2.96, P=0.005). Plasma ICAM-1 was essentially associated with the risk of myocardial infarction or coronary death and also with angina pectoris. Subjects with CRP presented elevated coronary risk only if ICAM-1 was high. An elevated level of VCAM-1 was not associated with any risk of future acute coronary event, or with angina pectoris. This data indicates that plasma levels of ICAM-1 may serve as risk markers for future coronary events whatever their clinical presentation and that risk is better defined using simultaneous measurements of ICAM-1 and CRP than any of these levels separately.

Synergistic effect of -174 G/C polymorphism of the interleukin-6 gene promoter and 469 E/K polymorphism of the intercellular adhesion molecule-1 gene in Italian patients with history of ischemic stroke.

Interleukin-6 (IL-6) and intercellular adhesion molecule-1 (ICAM-1) are involved in the pathogenetic mechanisms responsible for several ischemic cardiovascular disorders, including cerebral ischemia. IL-6 and ICAM-1 plasma levels and/or function may be genetically influenced. We sought to evaluate distribution and reciprocal interaction of IL-6 G/C gene promoter polymorphism and ICAM-1 E/K gene polymorphism in Italian patients with history of ischemic stroke. One hundred nineteen patients with history of ischemic stroke and 133 age- and sex-matched controls were studied. IL-6 and ICAM-1 genotypes were evaluated by polymerase chain reaction and restriction enzyme analysis. The GG genotype of -174 IL-6 G/C gene polymorphism was significantly associated with history of ischemic stroke at both univariate (P<0.0001) and multivariate analysis (odds ratio [OR], 8.6; P<0.0001). Additionally, the EE genotype of ICAM-1 E/K gene polymorphism was significantly more common in the group of patients with history of ischemic stroke (P=0.003) and was an independent variable associated with stroke history (OR, 4.0; P=0.002). Interestingly, a further increased risk of stroke was found in subjects who concomitantly carry the IL-6 GG and ICAM-1 EE genotypes (IL-6 GG/ICAM-1 EE double-homozygous subjects) (OR, 10.1; P=0.004). There is a synergistic effect of IL-6 G/C and ICAM-1 E/K gene polymorphisms in patients with stroke history. Reciprocal interactions between genotypes may contribute in determining the risk profile for cardiovascular diseases and may merit further investigation as potential therapeutic targets.