Serum Levels Of Adhesion Molecules Research Articles

Effects of marine-derived n–3 PUFA supplementation on soluble adhesion molecules: A systematic review and dose-response meta-analysis of randomized controlled trials

Long-chain n–3 poly unsaturated fatty acids have anti-inflammatory effects but their effects on serum levels of adhesion molecules are inconsistent and contradictory. In this updated systematic review and meta-analysis, marine sources of omega-3 fatty acids were pooled up to determine the effects of omega-3 supplementation on adhesion molecules. PubMed-Medline, SCOPUS, Web of Science and Google Scholar databases (from inception to April 2023) were searched and all RCTs investigating the effects of marine sources of omega-3, on blood concentrations of adhesion molecules were included and a meta-analysis undertaken. Forty-two RCTs were included involving 3555 participants aged from 18 to 75 years. Meta-analysis of 38 arms from 30 RCTs reporting serum concentrations of vascular cell adhesion molecule-1 (VCAM-1) showed a significant reduction after omega-3 supplementation (WMD: −1.26, 95% CI: −1.88 to −0.64 ng/mL, P < 0.001). Meta-analysis of 40 arms from 30 RCTs reporting serum concentrations of intercellular adhesion molecule-1 (ICAM-1) revealed a reduction following omega-3 supplementation, although it was not significant (WMD: −1.76, 95%CI: −3.68 to 0.16 ng/mL, P = 0.07). Meta-analysis of 27 arms from 21 trials showed no effect on E-selectin (WMD: 0.01, 95%CI: −0.02 to 0.04 ng/mL, P = 0.62). Pooling 15 arms from 11 RCTs showed a marginally significant reducing effect on P-selectin concentrations (WMD: −2.67, 95%CI: −5.53 to 0.19 ng/mL, P = 0.06). A considerable decrease in VCAM concentration was observed after omega-3 supplementation in this meta-analysis with a trend to decreases in both ICAM and P-selectin levels, with effects that may be significant depending on study design, and there was no effect on E-selectin.

Assessment of I-CAM1, V-CAM1, and E-selectin Serum Levels in Patients with Breast and Pelvic Cancer: A Case Control Study

Background: Breast and pelvic cancers are the most prevalent cancers among women globally. Several studies have reported on the effect of cell adhesion molecules on the growth, multiplication, invasion, and metastasis of tumor cells as well as inflammatory biomarkers, which are responsible for harmful inflammatory processes. Objectives: The purpose of the current study was to assess the serum levels of adhesion molecules intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin in patients with cancer before and after radiotherapy, compare these with the levels of healthy subjects, and consider the relationship of these levels with the tumor origin. Methods: The present case-control study investigated 14 patients with breast cancer and 14 patients with pelvic cancer who had been referred to Omid Teaching Hospital’s oncology clinic, Mashhad, Iran between 2015 and 2017. Evaluated by the ELISA method for ICAM-1, VCAM-1, and E-selectin were the serum samples of these 28 cancer patients before and after their course of radiotherapy treatment and the serum samples of the 28 healthy subjects who had no history of cancer, radiotherapy or the risk factor of coronary artery disease. Results: The ICAM-1, VCAM-1, and E-selectin serum levels of all patients with cancer before and after a course of radiotherapy were significantly higher than those of the control group (P-value ≤ 0.5). There was no significant difference between the two cancer groups before and after radiotherapy (P-value ≥ 0.05). Conclusions: The current study demonstrated that the serum levels of adhesion molecules in patients with cancer before and after radiotherapy increase significantly regardless of the initial location of the tumor.

Does Empagliflozin Modulate Leukocyte-Endothelium Interactions, Oxidative Stress, and Inflammation in Type 2 Diabetes?

Sodium-glucose co-transporter 2 inhibitors (iSGLT2) have been linked to cardiovascular risk reduction in patients with type 2 diabetes (T2D). However, their underlying molecular mechanisms remain unclear. This study aimed to evaluate the effects of empagliflozin, a novel potent and selective iSGLT-2, on anthropometric and endocrine parameters, leukocyte–endothelium interactions, adhesion molecules, ROS production, and NFkB-p65 transcription factor expression. According to standard clinical protocols, sixteen T2D patients receiving 10 mg/day of empagliflozin were followed-up for 24 weeks. Anthropometric and analytical measurements were performed at baseline, 12 weeks, and 24 weeks. Interactions between polymorphonuclear leukocytes and human umbilical vein endothelial cells (HUVECs), serum levels of adhesion molecules (P-Selectin, VCAM-1 and ICAM-1) and pro-inflammatory cytokines (TNF-α, IL-1β and IL-6), mitochondrial ROS levels, antioxidant enzymes (SOD1 and GPX1), and NFkB-p65 were measured. We observed a decrease in body weight, BMI, and HbA1C levels from 12 weeks of treatment, which became more pronounced at 24 weeks and was accompanied by a significant reduction in waist circumference and glucose. Leukocyte–endothelium interactions were reduced due to an enhancement in the leukocyte rolling velocity from 12 weeks onwards, together with a significant decrease in leukocyte rolling flux and adhesion at 24 weeks. Accordingly, a significant decrease in ICAM-1 levels, mitochondrial ROS levels, and IL-6 and NFkB-p65 expression was observed, as well as an increase in SOD1. This pilot study provides evidence of the anti-inflammatory and antioxidant properties of empagliflozin treatment in humans, properties which may underlie its beneficial cardiovascular effects.

The level of adhesion molecules in polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is characterized by dysfunction of the ovaries, hyperandrogenism and combination of metabolic disorders that increase the risk of developing cardiovascular diseases.The objective: of the investigation was to study the serum level of adhesion molecules (ICAM-1, VCAM-1 and E-selectin) in women with PCOS with different body weights as a marker of endothelial dysfunction, and their relationship with other factors of cardiovascular pathology.Materials and methods. 45 women with PCOS were examined, among whom a group of obese people – 23 women (age: 22,82±3,03 years, BMI 35,67±4,6) and a non-obese – 22 women (age: 22,81±2,03 years, BMI 22,35±2,16). The control group included 20 women aged 20,15±2,15 years, BMI 21,32±2,19. The serum level of ICAM-1, VCAM-1 and E-selectin was determined by the enzyme immunoassay. The significance of the differences of mean values was determined by the Student’s t-test. Correlation and multivariate regression analysis was used to assess the relationship between the studied factors,.Results. We revealed a significant increase of the serum level of adhesion molecules in obese and non-obese women with PCOS in comparison with women in the control group: ICAM-1 – +54,18%, +36,72%, respectively (p&lt;0,0001), VCAM-1 – +50,76%, +36,33% respectively (p&lt;0,0001), E-selectin – +40,24%, +29,56% respectively (p&lt;0,0001). The concentration of these factors was higher in obese women with PCOS compared to non-obese women with PCOS: ICAM-I – +12,76% (p=0,04), VCAM-1 – +10,58% (p=0,009), E-selectin – +8,24% (p=0,03); p&lt;0,05. The relationship was established between insulin content, HOMA and Caro index, lipid metabolism, hyperandrogenemia and an increase of serum level of adhesion molecules (p&lt;0,01).Conclusions. As a result of our study, an increase of serum level of adhesion molecules in PCOS was revealed, both in combination with obesity and normal body weight, which may be a manifestation of endothelial dysfunction in this pathological condition. An increase in the content of ICAM-1, VCAM-1, E-selectin may be associated with insulin resistance, dyslipidemia and hyperandrogenism.

GSTM1 Modulates Expression of Endothelial Adhesion Molecules in Uremic Milieu.

Deletion polymorphism of glutathione S-transferase M1 (GSTM1), a phase II detoxification and antioxidant enzyme, increases susceptibility to end-stage renal disease (ESRD) as well as the development of cardiovascular diseases (CVD) among ESRD patients and leads to their shorter cardiovascular survival. The mechanisms by which GSTM1 downregulation contributes to oxidative stress and inflammation in endothelial cells in uremic conditions have not been investigated so far. Therefore, the aim of the present study was to elucidate the effects of GSTM1 knockdown on oxidative stress and expression of a panel of inflammatory markers in human umbilical vein endothelial cells (HUVECs) exposed to uremic serum. Additionally, we aimed to discern whether GSTM1-null genotype is associated with serum levels of adhesion molecules in ESRD patients. HUVECs treated with uremic serum exhibited impaired redox balance characterized by enhanced lipid peroxidation and decreased antioxidant enzyme activities, independently of the GSTM1 knockdown. In response to uremic injury, HUVECs exhibited alteration in the expression of a series of inflammatory cytokines including retinol-binding protein 4 (RBP4), regulated on activation, normal T cell expressed and secreted (RANTES), C-reactive protein (CRP), angiogenin, dickkopf-1 (Dkk-1), and platelet factor 4 (PF4). GSTM1 knockdown in HUVECs showed upregulation of monocyte chemoattractant protein-1 (MCP-1), a cytokine involved in the regulation of monocyte migration and adhesion. These cells also have shown upregulated intracellular and vascular cell adhesion molecules (ICAM-1 and VCAM-1). In accordance with these findings, the levels of serum ICAM-1 and VCAM-1 (sICAM-1 and sVCAM-1) were increased in ESRD patients lacking GSTM1, in comparison with patients with the GSTM1-active genotype. Based on these results, it may be concluded that incubation of endothelial cells in uremic serum induces redox imbalance accompanied with altered expression of a series of cytokines involved in arteriosclerosis and atherosclerosis. The association of GSTM1 downregulation with the altered expression of adhesion molecules might be at least partly responsible for the increased susceptibility of ESRD patients to CVD.

A preliminary study of MMP-9 and sCD40L in patients with coronary slow flow.

To explore the relationship between coronary slow flow (CSF) and both matrix metalloproteinase-9 (MMP-9) and soluble cluster of differentiation 40 ligand (sCD40L). Between July 2016 and September 2019, 80 patients suspected of having coronary heart disease due to chest tightness or other symptoms of chest pain and discomfort were admitted to Nanjing Jiangbei People's Hospital and, following a coronary angiography, were diagnosed as having CSF. These patients were assigned to the coronary slow flow phenomenon (CSFP) group. The control group, or normal coronary flow (NCF) group, consisted of 80 patients with normal coronary angiography results. Following group assignment, enzyme-linked immunosorbent assays (ELISAs) were used to measure and compare the serum levels of sCD40L and MMP-9 between the two groups. Serum levels of sCD40L and MMP-9 in the CSFP group were significantly higher than those in the NCF group (PP<0.05). Additionally, serum levels of adhesion molecules and C-reactive protein (CRP) in the CSFP group were significantly higher than those in NCF group (P<0.05). There was a positive correlation observed between sCD40L levels and adhesion molecule levels in the CSFP group, however, there was no such correlation observed in the NCF group. The CSFP group also had a significantly higher corrected TIMI frame count (CTFC) compared with the NCF group (PP<0.05). Serum MMP-9 levels were higher in patients with CSF, and MMP-9 levels were positively correlated with CTFC. This suggests that chronic inflammation may play a role in CSF pathogenesis and that atherosclerotic plaques may be present in the coronary arteries of CSF patients. Additionally, serum levels of sCD40L, adhesion molecules, and CRP were higher in CSF patients, and CRP levels were positively correlated with CTFC. Adhesion molecule expression is promoted by sCD40L. Increased levels of sCD40L may therefore promote the development of CSF.

The effects of Elettaria cardamom supplementation on inflammatory markers and vascular function in patients with type 2 diabetes mellitus: A mechanism -based randomized clinical trial

Background & aimIn patients with type 2 diabetes mellitus (T2DM), endothelial dysfunction appears to be a common condition. Given the potential antioxidant and anti-inflammatory effects of dried fruits of Elettaria cardamom, the aim of this study was to investigate the effect of green cardamom supplementation on serum inflammatory markers and adhesion molecules in patients with T2DM. Materials & methodsIn a parallel, double-blind, randomized, placebo-controlled clinical trial, eighty-three overweight or obese type 2 diabetic patients with a body mass index (BMI) of 25-34.9 kg/m² were randomly allocated into an intervention (n = 41) or a control group (n = 42). The intervention and the placebo groups received 3 g of ground green cardamom’s fruit or rusk powder for 10 weeks, respectively. Physical activity level, dietary intake, anthropometric measurements, inflammatory markers [Interleukin 6 (Il-6), and Cluster of Differentiation 163 (CD163)] and serum adhesion molecules levels [intercellular adhesion molecule 1 (ICAM), vascular cell adhesion molecule 1 (VCAM), CD62 antigen-like family member (E-selectin) and matrix metalloproteinase 9 (MMP-9)] were measured. ResultsIn per-protocol (PP) analysis, after adjustment for confounders (gliclazide dose and duration of disease), the serum levels of VCAM (-244.5 ng/ml), ICAM (-72.3 ng/ml), E-selectin (-1.92 ng/ml) and IL-6 (-0.41 Pg/ml); (p < 0.05) significantly decreased in cardamom group compared to the controls. In addition, intention to treat (ITT) analysis showed that the serum levels of VCAM (-223.9 ng/ml), ICAM (-72.5 ng/ml), E-selectin (-1.71 ng/ml) and IL-6 (-0.37 Pg/ml); (p < 0.05) significantly reduced in cardamom group compared to the placebo group. No statistically significant difference was found between the two groups in term of the serum MMP-9 and CD163 levels. ConclusionsIn conclusion, the results suggested that cardamom supplementation improved serum levels of adhesion molecules and reduced some inflammatory biomarkers in T2DM patients.

Serum levels of subfatin in patients with type 2 diabetes mellitus and its association with vascular adhesion molecules

Subfatin is a newly discovered adipokine with insulin-sensitizing properties. Studies reported conflicting data with regard to the circulating levels and expression of Subfatin in the context of type 2 diabetes mellitus (T2DM) and obesity. The present study was conducted on 52 patients with T2DM, 36 prediabetes subjects, and 50 controls. The serum levels of Subfatin, adhesion molecules were measured by the ELISA technique. The serum Subfatin was lower in the T2DM and prediabetes groups. The serum levels of adhesion molecules were higher in the T2DM group. In addition, Subfatin demonstrated lower levels in obese patients with T2DM in comparison to lean T2DM patients. Furthermore, Subfatin showed a negative association with vascular adhesion molecules in prediabetes subjects and the T2DM group. A decrease in the serum Subfatin in T2DM patients and prediabetes subjects, and its association with vascular adhesion molecules suggested the possible role of Subfatin in diabetes and endothelial dysfunction.

Asymmetric dimethylarginine and soluble inter-cellular adhesion molecule-1 serum levels alteration following ginger supplementation in patients with type 2 diabetes: a randomized double-blind, placebo-controlled clinical trial.

Aims Patients with type 2 diabetes mellitus (T2DM) are prone to cardiovascular disease (CVD) due to inflammation process and oxidative stress. ADMA (Asymmetric dimethylarginine) and ICAM-1 (inter-cellular adhesion molecule-1) play an important role in CVD pathogenesis. Ginger as an anti-oxidant and anti-inflammation can effect on these biomarkers. The aim of present study was to characterize the effect of ginger supplementation on ADMA and ICAM-1 serum levels in patients with T2DM. Methods The present study is a randomized double-blind clinical trial which is conducted among 45 diabetic patients (nginger=23, nplacebo=22). The participants were randomly divided into two intervention and placebo groups which were received 2 g ginger powder and 2 g wheat flour for 10 weeks, respectively. ADMA and ICAM-1 concentration were measured by ELISA method. Results Ginger supplementation decreased ADMA serum levels significantly (P=0.002) and sICAM-1 serum levels marginally (P=0.097) in supplementation group after intervention. No significant difference was observed between placebo and supplementation groups. Conclusions Present study was conducted among patients with type 2 diabetes mellitus to investigate the effect of ginger supplementation on ADMA and sICAM-1 levels. There was a significant decrement in ADMA serum concentration and slight reduction in sICAM-1 levels in intervention group. The amount of reduction in both biomarkers was not statistically significant in between-groups comparison.

Puerarin inhibits the inflammatory response in atherosclerosis via modulation of the NF-κB pathway in a rabbit model.

The isoflavone puerarin [7-hydroxy-3-(4-hydroxyphenyl)-1-benzopyran-4-one 8-(β-D-glucopyranoside)] possesses many biological activities. In this study, we investigated the effects of puerarin on adhesion molecules (AMs), including serum levels of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and endothelial leukocyte adhesion molecule-1 (E-selectin), and the activation of nuclear factor kappa B (NF-κB) in rabbits with experimental atherosclerosis. In total, 24 rabbits were divided into control (standard diet), high-lipid diet (HLD), and PUE (HLD supplemented with puerarin) groups. At the end of weeks 0, 8, and 16, serum levels of AMs were measured. At the end of week 16, the thickness of the intima was detected. Protein and mRNA levels of AMs were checked by immunohistochemistry and RT-PCR, respectively. Protein levels of p65 NF-κB and phosphorylation of inhibitor-κB (I-κB) were investigated by Western blotting. Atherosclerotic lesions in the thoracic arch were found in the HLD and PUE groups, but not in the control group. Compared with the HLD group, the thickness of the intima in the PUE group was reduced. Our results indicate that puerarin reduced the protein and mRNA levels of AMs in this rabbit model. We also found that the reduced AM levels were due to inhibition of the phosphorylation and degradation of I-κB, resulting in reduced p65 NF-κB nuclear translocation. This study indicates that the effect of puerarin on the suppression of atherosclerosis was connected with an inhibited inflammatory response and reduced NF-κB activation.

Soluble Adhesion Molecules in Patients Coinfected with HIV and HCV: A Predictor of Outcome.

BackgroundHigher serum levels of adhesion molecules (sICAM-1 and sVCAM-1) are associated with advanced liver fibrosis in patients coinfected with human immunodeficiency virus and hepatitis C virus. We assessed the relationship between serum levels of adhesion molecules and liver-related events (LRE) or death, in coinfected patients.MethodsWe studied clinical characteristics and outcomes of 182 coinfected patients with a baseline liver biopsy (58 with advanced fibrosis) and simultaneous plasma samples who were followed for median of 9 years. We used receiver-operating characteristic (ROC) curves to calculate optimized cutoff values (OCV) of sICAM-1 and sVCAM-1, defined as the values with the highest combination of sensitivity and specificity for LRE. We used multivariate regression analysis to test the association between OCVs of sICAM-1 and sVCAM-1 and outcomes. The variables for adjustment were age, HIV transmission category, liver fibrosis, baseline CD4+ T-cell counts, antiretroviral therapy, and sustained virologic response (SVR).ResultsDuring the study period 51 patients had SVR, 19 had LRE, and 16 died. The OCVs for LRE were 5.68 Log pg/mL for sICAM-1 and 6.25 Log pg/mL for sVCAM-1, respectively. The adjusted subhazard ratio (aSHR) (95% confidence interval [CI]) of death or LRE, whichever occurred first, for sICAM-1 and sVCAM-1 > OCV were 3.98 ([1.14; 13.89], P = 0.030) and 2.81 ([1.10; 7.19], respectively (P = 0.030).ConclusionsSerum levels of sICAM-1 and sVCAM-1 can serve as markers of outcome in HIV/HCV-coinfected patients. Therapies targeting necroinflammatory damage and fibrogenesis may have a role in the management chronic hepatitis C.

Pentoxifylline decreases serum level of adhesion molecules in atherosclerosis patients.

Inflammation is involved in development, progression, and complications of atherosclerotic disease. Clinical studies have indicated that the level of monocyte chemoattractant protein 1 (MCP-1), IL-18, and adhesion molecules correlates with the severity of atherosclerosis and can predict future cardiovascular events. Experimental studies have shown pentoxifylline (PTX) reduces these factors in animal models. The purpose of the present pilot study was to evaluate effect of PTX on a group of inflammatory biomarkers in patients with coronary artery disease (CAD). Forty patients with angiographically documented CAD, who fulfilled inclusion and exclusion criteria, were entered in the double-blind, randomized, pilot clinical study. The patients were randomly given PTX (400 mg three times daily) or placebo (3 tab/day) for 2 months. Serum concentrations of MCP-1, IL-18, intercellular adhesion Molecule 1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1) were measured before and at the end of intervention by enzyme-linked immunosorbant assay. Our study showed that the serum levels of ICAM-1 and VCAM-1 was decreased in the study population after two-month treatment (P<0.05). Based on the results of our pilot study, administration of PTX in CAD patients significantly decreases adhesion molecules levels.

The effects of iodixanol and iopamidol on adhesion molecule serum levels in patients with angina pectoris undergoing coronary angiography: a randomized study

To compare intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) serum levels between patients with stable (SAP) and unstable angina pectoris (USAP) undergoing coronary angiography (CAG), investigate effects of CAG on ICAM-1, VCAM-1 levels in SAP, USAP patients; probable different effects of non-ionic radiocontrast media (RCM), iso-osmotic iodixanol and low osmolar iopamidol, on these adhesion molecules (AM). In this randomized, prospective study, 2 groups consisting of patients with SAP (n=22) and USAP (n=22) undergoing CAG were included. For halves of each group iopamidol, for the other halves iodixanol were used as RCM, in turn for randomization. The patients were divided into 4 subgroups according to clinical presentations and used RCM(SAP-iodixanol, SAP-iopamidol USAP-iodixanol, USAP-iopamidol). ICAM-1, VCAM-1 levels were measured just before and 12 hours after CAG. Repeated measurements were compared with two-way ANOVA test. Baseline VCAM-1 concentration was higher in USAP group than SAP group (p=0.001). ICAM-1, VCAM-1 concentrations increased significantly following CAG in SAP, USAP groups. ICAM-1, VCAM-1 concentration increments; didn't reach statistical significance in SAP-iodixanol subgroup, reached a borderline significance in SAP-iopamidol subgroup (p=0.06). In USAP-iodixanol subgroup; only VCAM-1 (p<0.001), in USAP-iopamidol subgroup; ICAM-1 (p=0.009), VCAM-1 (p=0.006) levels increased significantly following CAG. No complication was observed. To our knowledge, this is the first study indicating ICAM-1, VCAM-1 inducing effect of CAG in patients with SAP, USAP and differential effects of iodixanol and iopamidol on ICAM-1, VCAM-1 serum levels. Further studies are needed to clarify the effects of CAG and different RCM on vascular inflammation, vessel injury, serum AM levels and their clinical significance. This study should be taken as a pilot, hypothesis-generating study.

Inflammatory activation and recovering BKV-specific immunity correlate with self-limited BKV replication after renal transplantation

As BKV-associated nephropathy has emerged as an important cause of allograft failure, it has been of major importance to find immune mechanisms suitable to identify kidney transplant recipients (KTRs) at increased risk of BKV replication. We monitored 29 KTRs with seven measurements during the first year post-transplantation. BKV-specific T cells directed to 5 BKV proteins were analyzed in an interferon-γ ELISPOT assay. BKV-specific antibodies were measured using an ELISA. The extent of immunosuppression and inflammatory activation were quantified by measures of immune function including lymphocyte subpopulations, IP-10, and adhesion molecule serum levels. All 5 BKV-specific T cells increased significantly from diagnosis to resolution of BKV replication (P<0.001). While antistructural T cells were significantly higher in KTRs with BKV replication (P<0.05), no differences were observed for antismall t- and large T-antigen-directed T cells (P>0.05). Interestingly, 65% of KTRs without BKV replication showed transient appearance of antismall t- and large T-antigen-directed T cells. Although no significant differences were observed for T-cell subpopulations and adhesion molecules, IP-10 levels increased significantly during BKV replication (P<0.05). Assessment of BKV-specific T cells identifies recovering BKV-specific immunity in KTRs with BKV replication and suggests their protective ability in KTRs without BKV replication. Increases in IP-10 levels stress the importance of infiltrating inflammatory leukocytes in the regulation of BKV replication and point to inflammatory activation in the pathogenesis of BKV replication.

Levels of soluble adhesion molecules and their associations in inflammatory myositis

Vidya S. Limaye, Claudine S. Bonder, Wai Y. Sun, Susan Lester, Peter J. Roberts-Thomson And Peter Blumbergs

Effect of an Exercise Program, on Hemodynamic, Metabolic and Inflammatory Markers in Obese Mexican Adolescents

Background: Obesity prevalence has increased in Mexican adolescents. This disease is associated with a chronic inflammatory response, which has been proposed to have an important role in cardiovascular disease. The aim of this study was to evaluate the short term effect of a moderate-intensity physical activity program on hemodynamic, metabolic, and inflammatory markers in obese adolescents. Findings: We performed a longitudinal study in 43 healthy obese adolescents (26 female and 17 male). The study was conducted at the Mexican Institute of Social Security in Leon, Mexico. Subjects were submitted to aerobic exercise training during 90 minutes for 16 weeks, 5 days per week. Before and after the intervention program, hemodynamic, metabolic and inflammatory parameters were measured. Body weight was reduced by 4%. Blood pressure, insulin, insulin resistance, C reactive protein, interleukine 6, intracellular adhesion molecule-1 and vascular cell adhesion molecule-1 serum levels significantly decreased independently of gender while adiponectin levels increased. In the multiple regression analysis, the increase in adiponectin levels and the decrease in body mass index were related to systolic blood pressure levels (R2= 0.26; p=0.001), while final maximum O2 consumption rate and final systolic blood pressure levels were related to decrease in C reactive protein levels (R2= 0.79; p=0.0001). Conclusions: A moderate-intensive exercise for 90 minutes a day at short term significantly diminished adiposity, hemodynamic, metabolic, and inflammatory markers in obese adolescents.

Prediction of Residual Valvular Lesions in Rheumatic Heart Disease: Role of Adhesion Molecules

Rheumatic heart disease (RHD) is a chronic condition characterized by fibrosis and scarring of the cardiac valves and damage to the heart muscle, leading to congestive heart failure and death. This prospective cohort study was conducted to investigate the possible relation between the levels of serum adhesion molecules and acute rheumatic fever (ARF) carditis, valvular insult severity, and residual valvular lesion after improvement of rheumatic activity. Serum levels of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin were assayed by enzyme-linked immunoassay (ELISA) for 50 children with ARF carditis during activity and after improvement and for 50 healthy children as control subjects. After the acute attack, patients were followed up regularly to detect residual valvular lesion. The serum levels of these adhesion molecules were significantly higher in the patients than in the control group (p<0.001). In addition, the levels of serum adhesion molecules were significantly higher in the patients with severe carditis than in the patients with mild to moderate carditis (p<0.001). Among the severe carditis group, the level of serum adhesion molecules was significantly higher among the patients with heart failure than among the patients without heart failure (p<0.001). Furthermore, the pretreatment serum levels of ICAM-1 and VCAM-1 were significantly higher among the patients with residual valve lesion (p=0.002) than among those without the lesion (p<0.001). The cutoff values were obtained for the prediction of residual valvular lesion (ICAM-1, >1,032.3μg/ml; VCAM-1, >3,662.3μg/ml; E-selectin, >104.8μg/ml). Finally, by combining the three adhesion molecules in a single prediction model, the highest area under the curve (AUC)±standard error (SE) was obtained (0.869±0.052), and the positive likelihood ratio for having a residual valvular lesion was increased (17.33). Levels of serum adhesion molecules could predict residual valvular lesions in RHD patients. The authors recommend that the serum level of adhesion molecules be measured in all cases of ARF carditis.

Endothelial dysfunction is associated with increased levels of biomarkers in essential hypertension

To assess the correlation between endothelial dysfunction and the serum levels of biomarkers of inflammation, remodelling and oxidative stress in essential hypertension, 78 treatment-naïve essential hypertensives (mean age 43 years) underwent measurement of endothelial dysfunction, using the maximal acetylcholine-induced forearm vasodilation and serum levels of adhesion molecules, selectins, chemokines, metalloproteinases, copper, zinc, selenium, vitamins, homocysteine, malondialdehyde, erythrocyte glutathione peroxidase and erythrocyte superoxide dismutase. Mean (+/-s.e.m.) maximal acetylcholine-induced vasodilation was 367+/-20%. Patients with a more impaired acetylcholine-dependent vasodilation (first tertile) had increased levels of e-selectin (P=0.009), p-selectin (P<0.001), monocyte chemotactic protein type 1 (MCP-1; P=0.012) and the tissue inhibitor of metalloproteinases type 1 (TIMP-1; P=0.044), which in turn showed significant inverse correlations with maximal endothelium-dependent vasodilation. Serum levels of selenium (P=0.012), vitamin C (P=0.038), erythrocyte glutathione peroxidase (P<0.001) and superoxide dismutase (P=0.022) activities were reduced in patients with a more impaired endothelium-dependent vasodilation. Recently diagnosed treatment-naïve essential hypertensives showed a relationship between the endothelial dysfunction, serum markers of inflammation and remodelling and levels of antioxidant substances. These could be potentially helpful markers of high risk in hypertensive patients.

Daily consumption of milk enriched with fish oil, oleic acid, minerals and vitamins reduces cell adhesion molecules in healthy children

Background and aims Several studies have suggested that polyunsaturated fatty acids, vitamins and minerals have beneficial effects on lipid profile and systemic inflammation in adults. Methods and results We examined the effects of a daily intake of milk enriched with long-chain polyunsaturated fatty acids, oleic acid, carbohydrates, vitamins, minerals and low in saturated fatty acids (SFAs) for 5 months, on several cardiovascular (CVD) risk biomarkers in healthy children aged 8–14 years. In a randomized double-blind placebo-controlled trial, a total of 107 children of both genders were assigned to two study groups: 1) a supplemented group (SG, n = 53) who consumed 0.6 L/day of an enriched dairy product, and 2) a control group (CG, n = 54) who consumed 0.6 L/day of standard whole milk. Both groups consumed the dairy drinks for 5 months, in addition to their usual diet. Serum levels of adhesion molecules as indices of vascular endothelial cell activation were assessed in both groups at 0 and 5 months as well as white blood cell counts, lipid profile, serum proteins, total serum calcium, 25-OH vitamin D, glucose, insulin and adiponectin. In the enriched dairy drink supplemented group, adhesion molecules E-selectin and ICAM-1 as well as lymphocyte levels decreased while plasma docosahexaenoic acid (DHA) and serum calcium concentrations increased. In the control group, serum total protein, transferrin, total cholesterol, HDL-cholesterol and adiponectin concentrations decreased. Conclusion The consumption of a milk enriched with fish oil, oleic acid, minerals and vitamins reduced indices of endothelial cell activation in the studied group of healthy children.

Increased levels of Vascular Cell Adhesion Molecule-1 (VCAM-1) and Inter-Cellular Adhesion Molecule-1 (ICAM-1) Correlate with Advanced Disease Features and Poor Survival in Newly Diagnosed Patients with Multiple Myeloma. Reduction Post-Bortezomib- and Lenalidomide-Based Regimens.

Abstract 1824Poster Board I-850Interactions between myeloma (MM) cells and bone marrow stromal cells (BMSCs) are strongly implicated in the biology of MM. The aim of this study was to evaluate the serum levels of adhesion molecules, such as VCAM-1 (CD106), ICAM-1 (CD54), P-, L- and E-selectin in patients with MM and explore possible correlations with clinical and laboratory data. The study population included 87 newly diagnosed patients (42M/45F; median age 68 years): 59 with symptomatic MM, 21 with asymptomatic MM (AMM) and 7 with MGUS, as well as 21 MM patients at first relapse (11M/10F, median age 69 years) who received the combination of bortezomib/dexamethasone (VD) and 20 MM patients at first relapse (11M/9F, median age 68.5 years) who were treated with the combination of lenalidomide plus low-dose dexamethasone (Rd). The aforementioned adhesion molecules were measured in the serum of newly-diagnosed patients before the administration of any kind of therapy, in relapsed patients on Day 1 of cycle 1 and on the last day of cycle 4 and in 43 healthy controls using ELISA method (R&D Systems, Minneapolis, MN, USA). Patients with newly-diagnosed or relapsed MM had increased levels of all studied molecules compared to controls (p<0.01), while in MGUS only serum VCAM-1 and ICAM-1 levels were elevated compared to controls (p<0.01). Newly-diagnosed patients with symptomatic MM had increased levels of VCAM-1 (mean±SD: 1168.5±810.4 ng/ml) and ICAM-1 (371.0±162.7 ng/mL) when compared to AMM patients (642.6±340.9 ng/ml, p<0.0001; and 274.4±65.5 ng/ml, p=0.002, for VCAM-1 and ICAM-1, respectively) and to MGUS patients (629.8±228.5 ng/ml, p=0.012; and 247.9±53.9, p=0.009, for VCAM-1 and ICAM-1, respectively). Furthermore, newly-diagnosed symptomatic MM had increased levels of E-selectin (43.2±20.0 ng/ml) compared to AMM (33.6±16.6 ng/ml, p=0.047). VCAM-1 was lower in patients with ISS-1 (768.2±225.1 ng/ml) compared to patients with ISS-2 (1121.7±991.2 ng/ml) and ISS-3 (1456.8±785.7 ng/ml; ANOVA p=0.04), while P-selectin was higher in ISS-1 (172.7±76.6 ng/ml) compared to ISS-2 (118.7±75.5 ng/ml) and ISS-3 MM (108.3±76.4; ANOVA p=0.042). For all newly-diagnosed patients, there was a strong correlation between VCAM-1 and ICAM-1 (r=0.598, p<0.0001). Serum VCAM-1 showed strong positive correlations with β2-microglobulin (r=0.564, p<0.0001), urea (r=0.384, p=0.001) and creatinine (r=0.376, p=0.001) and negative correlation with Hb (r=-0.346, p=0.002). Similarly, ICAM-1 positively correlated with β2-microglobulin (r=0.340, p=0.003), creatinine (r=0.290, p=0.01) and urea (r=0.254, p=0.025), and negatively correlated with Hb (r=-0.237, p=0.037). Serum P-selectin positively correlated with platelet counts (r=0.555, p<0.0001), Hb (r=0.416, p<0.0001) and albumin (r=0.270, p=0.017), but negatively correlated with β2-microglobulin (r=-0.383; p=0.001) and creatinine (r=-0.294, p=0.009). For L-selectin there was a positive correlation with albumin (r=0.370; p=0.001). The median follow-up of patients with newly-diagnosed symptomatic MM was 22 months (range: 4-54 months) and the median OS was 42 months. Increased levels of VCAM-1, ICAM-1 and L-selectin predicted for inferior survival. In particular, patients with VCAM-1 >1358.5 ng/ml had a median OS of 20 months in comparison to 42 months of all others (p=0.006), while patients with elevated ICAM-1 (>400.6 ng/ml) had a median OS of 13 months compared to 42 months of all others (p<0.0001) and patients with L-selectin >928.2 ng/ml had a median OS of 23 months compared to 42 months of all others (p=0.024). MM patients at first relapse had increased levels of VCAM-1 and ICAM-1 even compared to newly-diagnosed symptomatic MM patients (p<0.01). Both BD and Rd administration reduced dramatically serum VCAM-1 and ICAM-1 after 4 cycles of therapy (p<0.01 for all comparisons) but had no effect on the levels of selectins. The reduction of VCAM-1 and ICAM-1 was more pronounced in responders than in non-responders (p=0.032). In conclusion, patients with newly diagnosed MM have increased serum levels of VCAM-1 and ICAM-1 that correlate with advanced disease features and poor survival suggesting an important role in the biology of the disease. Selectins seem also to participate in MM pathogenesis. The administration of novel agents such as bortezomib and lenalidomide resulted in the reduction of VCAM-1 and ICAM-1 and supports a direct effect on the adhesion of MM cells to BMSCs. DisclosuresNo relevant conflicts of interest to declare.