Serum Levels Of VCAM-1 Research Articles

A comparative study of anti-atherosclerotic/anti-inflammatory effect of irbesartan and rosuvastatin in hypercholesterolemic male rabbits

Objective: To evaluate the potential protective effect of irbesartan on atherosclerotic progression using rosuvastatin as a positive control.
 Methods: Twenty local domestic rabbits were randomly divided into four groups, five rabbits per each group. The first group (I), rabbits were receiving normal diet; the second group (II), rabbits were receiving 2 % cholesterol diet; the third group (III), rabbits were receiving rosuvastatin and 2% cholesterol diet and; the fourth group (IV), rabbit were receiving irbesartan and 2% cholesterol diet. Serum level of cholesterol, triglycerides, LDL, VLDL and HDL were determined after 12 weeks of the study. Serum level of high sensitive C-reactive protein, ICAM1and VCAM1 were measured after 12 weeks of the study. Total antioxidant activity was also determined. Aortic tissue sent for histopathological examination of atherosclerosis lesion.
 Result: Data of this study have showed that atherogenic diet caused an increase in serum level of TC, LDL, VLDL and TG and a decrease in serum level of HDL. Treatment of rabbits with irbesartan caused substantial decrease in serum lipid profile compared with untreated rabbit receiving atherogenic diet. No significant difference was seen between irbesartan- and rosuvastatin-treated rabbits in all lipid parameters measured with the exception that the HDL level in rosuvastatin-treated rabbits was significantly higher than that of irbesartan-treated rabbits. Rabbit treated with irbesartan showed a significant decrease in the serum level of high sensitive C-reactive protein, ICAM1, VCAM1 and aortic total antioxidant capacity when compared with untreated group. No significant difference was seen between irbesartan- and rosuvastatin-treated rabbits in all these inflammatory parameters measured. Histopathological examination showed that irbesartan decreased atherogenic lesion significantly when compared with untreated rabbits.
 Conclusion: Irbesartan has a potential protective effect against atherosclerosis via decreasing lipid oxidation and inflammatory mediators. In terms of lipid lowering and anti-inflammatory effects, irebsartan has similar pattern of effectiveness to rosuvastatin.

Association between the simultaneous decrease in the levels of soluble vascular cell adhesion molecule-1 and S100 protein and good neurological outcomes in cardiac arrest survivors.

ObjectiveThis study aimed to determine whether simultaneous decreases in the serum levels of cell adhesion molecules (intracellular cell adhesion molecule-1 [ICAM-1], vascular cell adhesion molecule-1 [VCAM-1], and E-selectin) and S100 proteins within the first 24 hours after the return of spontaneous circulation were associated with good neurological outcomes in cardiac arrest survivors.MethodsThis retrospective observational study was based on prospectively collected data from a single emergency intensive care unit (ICU). Twenty-nine out-of-hospital cardiac arrest survivors who were admitted to the ICU for post-resuscitation care were enrolled. Blood samples were collected at 0 and 24 hours after ICU admission. According to the 6-month cerebral performance category (CPC) scale, the patients were divided into good (CPC 1 and 2, n=12) and poor (CPC 3 to 5, n=17) outcome groups.ResultsNo difference was observed between the two groups in terms of the serum levels of ICAM-1, VCAM-1, E-selectin, and S100 at 0 and 24 hours. A simultaneous decrease in the serum levels of VCAM-1 and S100 as well as E-selectin and S100 was associated with good neurological outcomes. When other variables were adjusted, a simultaneous decrease in the serum levels of VCAM-1 and S100 was independently associated with good neurological outcomes (odds ratio, 9.285; 95% confidence interval, 1.073 to 80.318; P=0.043).ConclusionA simultaneous decrease in the serum levels of soluble VCAM-1 and S100 within the first 24 hours after the return of spontaneous circulation was associated with a good neurological outcome in out-of-hospital cardiac arrest survivors.

Effect of Synbiotic and Probiotic Supplementation on Serum Levels of Endothelial Cell Adhesion Molecules in Hemodialysis Patients: a Randomized Control Study.

The aim of this study was to investigate the effect of synbiotic and probiotic supplementation on serum vascular dysfunction and necrosis markers in hemodialysis (HD) patients. In this randomized, double-blind, placebo-controlled trial, 75 HD patients were randomly assigned to either the synbiotic or probiotic or placebo group. The patients in the synbiotic group received 15g of prebiotics and 5g probiotic powder containing Lactobacillus acidophilus strain T16 (IBRC-M10785), Bifidobacterium bifidum strain BIA-6, Bifidobacterium lactis strain BIA-6, Bifidobacterium longum strain LAF-5 (2.7 × 107CFU/g each) in sachets (n = 25), whereas the probiotic group received 5g probiotics same to the first group with 15g of maltodextrin powder in sachets (n = 25) and the placebo group received 20g of maltodextrin powder in sachets (n = 25) for 12weeks. At baseline and the end of the study, serum concentrations of soluble intercellular adhesion molecule type 1 (sICAM-1), soluble vascular cell adhesion molecule type 1 (sVCAM-1), cytokeratin 18 (CK-18) as the necrosis marker, uric acid, and phosphate levels were measured. Feces also were collected for microbiota colony counting. Serum ICAM-1 level reduced significantly in the synbiotic group after the intervention period (P = 0.02), and this reduction was significantly different in the synbiotic group in comparison to the placebo group (P = 0.03). Serum levels of VCAM-1 and CK-18 were not significantly different between the groups. However, the reduction in serum levels of VCAM-1 in the synbiotic group was significantly higher in comparison to the placebo group (P = 0.01). Multivariate linear regression analysis revealed that ∆ phosphate was the sole independent determinant of ∆ICAM-1 (P = 0 < 001). The study indicated that synbiotic supplementation reduced serum ICAM-1 level, which is a risk factor for cardiovascular diseases in HD patients, but has no effect on the necrosis marker. Trial registration: www.irct.ir (IRCT2017041233393N1).

Anti-atherosclerosis of oligomeric proanthocyanidins from Rhodiola rosea on rat model via hypolipemic, antioxidant, anti-inflammatory activities together with regulation of endothelial function

BackgroundRhodiola rosea has been used as a traditional medicine for a long history. Previous studies on oligomeric proanthocyanidins from Rhodiola rosea (OPCRR) have showed that it exhibited significant free radical-scavenging activities, antioxidant activities in aging mice and lipid lowering effects. Hypothesis/PurposeWe hypothesized that OPCRR can improve the atherosclerosis pathological in rats. In the present study, we investigated the effects of OPCRR on the serum lipid profiles, oxidant stress status, inflammatory cytokines and atherosclerotic mediators, and endothelial dysfunction as well as changes in abdominal aorta of atherosclerosis rats. MethodsThe major components of OPCRR were analyzed by using infrared spectrum and HPLC-ESI-MS. The atherosclerosis rat model was induced by high fat and vitamin D3 feeding for 9 weeks and two OPCRR doses (60 and 120 mg/kg b.w.) were orally administered daily for 9 weeks. The rats were then sacrificed and the blood was collected via abdominal aorta and serum was separated by centrifugated for biochemical analysis. Part of the aorta tissues were excised immediately for histopathological examination and western blotting. ResultsCompared to model group, OPCRR treatments significantly decreased the serum lipid profiles including total cholesterol, total triglycerides, low-density lipoprotein cholesterol (LDL-C) and ox-LDL and increased the high-density lipoprotein cholesterol (HDL-C); significant increased serum antioxidant enzymes (SOD and GSH-Px) and decrease of MDA content as a product of lipid peroxidation; lowered serum levels of TNF-α, IL-1β, IL-6, ICAM-1 and VCAM-1 and enhanced IL-10 level; increased the serum release of nitric oxide and expression of iNOS in aortic, whereas decreased the expression of eNOS. ConclusionOPCRR can improve the progress of atherosclerosis by regulation of lipid metabolism, restoring of the antioxidant capacities, and attenuation of pro-inflammatory cytokines and chemcytokines release, and improving the endothelial dysfunction indicated by nitric oxide system.

Endothelial activation and infarct size at the acute phase of myocardial infarction

Acute myocardial infarction (MI) leads to an intense inflammatory response with endothelial cell activation. Vascular cell adhesion protein 1 (VCAM-1), E-selectin, intercellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein 1 (MCP-1) promote the adherence of leucocytes especially monocytes, in the infarcted area which may increase infarct size (IS). Our objective was to evaluate the kinetic of endothelial cell activation markers at the acute phase of ST-elevated MI (STEMI) and their relationship with IS and Major Adverse Cardiac Event (MACE). Blood sample of 182 STEMI patients were collected at admission and four hours after reperfusion. Infarct Size (IS) was assessed in all patients using cardiac Magnetic Resonance Imaging (cMRI) one month after discharge. We performed ELISA quantification of the main markers of endothelial cell activation in serum: VCAM-1, E-selectin, ICAM-1 and MCP-1. Patients mean age was 58 ± 11 years with 77% males. Median levels of each marker at admission reached 165.3 ng/mL interquartile range (IQR) [127.0–193.3] for VCAM-1, 140.6 ng/mL IQR [104.6–196.6] for ICAM-1, 15.3 ng/mL IQR [10.2–23.3] for E-selectin and 53.8 pg/mL IQR [34.7–90.5] for MCP-1. VCAM-1 and MCP-1 serum levels significantly increased four hours after admission (respectively +6% and +32%). E-selectin and ICAM-1 levels did not change four hours after admission compared to admission. Only VCAM-1 was significantly correlated with IS assessed by cMRI ( r = 0.26, P = 0.0004) and inversely correlated with left ventricular ejection fraction ( r = −0.16, P = 0.04). However, VCAM-1 level and other markers were not associated with MACE. MI is associated with endothelial cell activation. VCAM-1 and MCP-1 significantly increased at the acute phase of MI whereas E-selectin and ICAM-1 levels are stable. Only VCAM-1 serum level was correlated with IS. However, none of these markers was associated with the occurrence of MACE.

VCAM-1 as an Endothelial Factor for Diagnosis of Dementia in Parkinson’s Disease

Background: Cognitive changes are often reported in Parkinson’s disease (PD). Numerous studies showed that there are changes in the patterns of inflammation when vascular dementia progressed, but the role of inflammation in PD is unknown. Methods: 75 consecutive diagnosed PD patients included. Patients divided into idiopathic PD (n=55) and PDD (n=20) based on DSM–IV criteria for diagnosis of dementia. Serum levels of vascular and inflammatory biomarkers for interleukin-6 (IL-6), high sensitivity-C reactive protein (hs- CRP), soluble intracellular cell adhesion molecule (ICAM-1), soluble vascular cell adhesion molecule (VCAM-1) investigated by ELISA assay and compared between PD and PDD. Result: The significant enhancement of the VCAM-1 only found in serum of PDD compared to PD (56/06 ± 58/16 ng/ml vs. 30/43 ± 38/30, P=0/04), even after adjustment age, gender and hypertension (OR=1/01, P=0/05). Cut-off point of VCAM-1 levels was equal to or greater than as 40/14 ng/ml for differentiating dementia in PD from PD without dementia with sensitivity and specificity were 73%, 64%. Conclusion: PDD patients had significant higher levels of VCAM-1 than PD, suggesting the serum levels of VCAM-1 may be a useful marker for PDD diagnosis. Future studies are needed to investigate possible association betweenVCAM-1 levels in PDD in larger sample size.

Silencing LncRNA AK139328 protects vascular endothelial cells from ischemia-reperfusion injury by increasing PI3K/Akt signaling

// Zeng-Yang Pei 1 , Sheng-Hao Wang 1 , Yan Mao 2 , Qi Li 1 , Zi-Heng Wu 3 and Xiang-Tao Zheng 3 1 Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou 310058, P.R. China 2 Pet Shield Animal Hospital, Xihu District, Hangzhou 310000, P.R. China 3 Department of Vascular Surgery, The First Affiliated Hospital of Medical School of Zhejiang University, Hangzhou 310003, P.R. China Correspondence to: Zeng-Yang Pei, email: peizengyang@zju.edu.cn Keywords: LncRNA AK139328; vascular endothelial cells; ischemia-reperfusion; PI3K/Akt signaling pathway; rat model Received: July 12, 2016 Accepted: October 17, 2017 Published: January 02, 2018 ABSTRACT We investigated the effects of lncRNA AK139328 and PI3K/Akt signaling during rat hindlimb ischemia-reperfusion (I/R) injury. Rat vascular endothelial cells (VECs) subjected to oxygen-glucose deprivation showed high lncRNA AK139328 expression and decreased PI3K/Akt signaling, whereas lncRNA AK139328 knockdown increased PI3K/Akt signaling in VECs. Correspondingly, gastrocnemius muscles from rats subjected to hindlimb I/R showed high levels of lncRNA AK139328 and low PI3K/Akt/eNOS signaling. I/R also increased serum levels of TNF-α, VCAM-1 and malondialdehyde, serum creatine kinase activity and the number of circulating endothelial cells (CECs). Gastrocnemius tissue from rats subjected to I/R exhibited inflammation, apoptosis and trauma with loosely attached, swollen VECs associated with inflammatory immune cells. LncRNA AK139328 knockdown increased PI3K/Akt/eNOS signaling in gastrocnemius muscles subjected to I/R, and decreased serum levels of TNF-α, VCAM-1 and malondialdehyde, serum creatine kinase activity and numbers of CECs. LncRNA AK139328 knockdown also decreased inflammation, apoptosis and trauma in gastrocnemius muscles, which showed tightly attached VECs that were not associated with inflammatory immune cells. Inhibition of PI3K/Akt signaling by wortmannin or LY294002 reversed the effects of lncRNA AK139328 knockdown. In conclusion, I/R induces expression of lncRNA AK139328, which suppresses PI3K/Akt signaling required to prevent I/R-related pathology in VECs.

Endocan: A Novel Marker of Endothelial Dysfunction in C1-Inhibitor-Deficient Hereditary Angioedema

Background: Hereditary angioedema (HAE) related to C1-inhibitor deficiency is a rare autosomal dominant disorder. Vascular cell adhesion molecules (VCAM) are known as endothelial activation markers. Endocan (also called ESM-1) is proposed as an endothelial dysfunction indicator. We aimed to investigate endothelial activation in attack-free periods in HAE patients by measuring their levels of endocan and VCAM-1. Methods: Twenty-six HAE patients (22 female, mean age 40 ± 13 years) and 38 healthy control patients (13 female, mean age 36.9 ± 12 years) were included in the study. Peripheral blood samples were collected from HAE patients during symptom-free periods and control subjects. Endocan and VCAM-1 levels were measured using the enzyme-linked immunosorbent assay method. Results: The median serum levels of endocan (647 ± 101 ng/mL) and VCAM-1 (500 ± 79 ng/mL) in the HAE patients were significantly higher than in the control patients (391 ± 41 and 325 ± 4; p < 0.001 for both). Conclusion: The increased endocan and VCAM-1 levels may reflect an endothelial activation even in attack-free periods in HAE patients.

P-selectin, endocan, and some adhesion molecules in obese children and adolescents with non-alcoholic fatty liver disease

There is increasing evidence for a direct relationship between the vascular system and non-alcoholic fatty liver disease (NAFLD). The aim of this study was to investigate endocan and adhesion molecules such as P-selectin derived from the endothelium and platelets in obese children and adolescents with NAFLD. One hundred obese patients and 40 lean controls were enrolled. The obese subjects were divided into two subgroups based on the presence or absence of fatty liver. Blood samples were assayed for endocan, P-selectin, platelet-derived growth factor (PDGF), intercellular cell adhesion molecule (ICAM)-1, and vascular cell adhesion molecule (VCAM)-1. Obese patients with NAFLD presented higher ALT and insulin levels, as well as more profound dyslipidemia when compared with their counterparts without NAFLD. Serum levels of high-sensitivity C-reactive protein, VCAM-1 and ICAM-1 were found increased in both obese groups, regardless of NAFLD. In obese subjects with NAFLD, decreased P-selectin levels (51.6 ± 4.14 ng/mL) were detected as compared with the obese (72.3 ± 4.23) and control (74.2 ± 6.97) subjects. Furthermore, circulating P-selectin levels were closely associated with endocan levels (r = 0.852, p < 0.001). Childhood obesity leads to vascular inflammation and therefore may cause a predisposition to atherosclerosis at an early age. The possible outcome of decreased P-selectin levels with NAFLD development must be further investigated.

The Effect of Vitamin D Administration on Intracellular Adhesion Molecule-1 and Vascular Cell Adhesion Molecule-1 Levels in Hemodialysis Patients: A Placebo-controlled, Double-blinded Clinical Trial.

Objective:Vitamin D deficiency is quite common among end-stage renal disease (ESRD) patients, and Vitamin D administration could reduce morbidity and mortality in these patients through different mechanisms. Cardiovascular diseases are the most common cause of mortality in these patients that are caused by vascular injuries. Intracellular adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM) are vascular inflammation indicators. The goal of this study is to find the effect of Vitamin D administration on ICAM-1 and VCAM-1 serum levels in ESRD patients on hemodialysis.Methods:The current study is a double-blind, randomized, placebo-controlled clinical trial on 64 patients in two groups of control and treatment. Serum levels of Vitamin D, ICAM-1, and VCAM-1 were measured before and after the study. Treatment group was treated with Vitamin D pearls while control group underwent treatment with placebo pearls. Average serum levels of Vitamin D, ICAM, and VCAM were measured in both groups before and after the study and were analyzed by ANOVA, paired t-test, and Chi-square test using SPSS software.Findings:Sixty-four ESRD patients were recruited for this study consisting of 32 male and 32 female subjects within the ages of 18 and 76 years. The change in serum level of Vitamin D was significant in treatment group (P = 0.001) but not in control group (P > 0.05). Serum levels of ICAM and VCAM also changed significantly in treatment group (P = 0.001) but not in control group (P > 0.05)Conclusion:Based on the findings of this study, it could be said that Vitamin D administration in ESRD patients may increase serum level of Vitamin D up to four times. It also reduces serum levels of ICAM and VCAM which might improve the vascular condition of these patients.

Agmatine Ameliorates Nicotine Induced Lung Injury in Rats through Decrease TGF-ß1 and Bax Immunoexpression and by Anti-oxidative Sress Pathway: Histological, Immunohistochemical and Biochemical Study

Introduction: Nicotine (NIC), the chief alkaloid in tobacco, believed to be an active agent responsible for lungassociated diseases. This protocol targeted to analyze the ameliorating effect of agmatine (AG) on NIC induced lung damage. Mateiral and methods: Forty-five adult male rats were divided into: Control group received intraperitoneal (IP) injection of distilled water, 2) NIC group recieved NIC (10 mg/kg/day) IP and 3) (NIC+AG) group treated by AG (10 mg/kg/day) orally+NIC (10 mg/kg/day) by IP injection for 9 weeks. Total serum protein, triglycerides (TGs), total cholesterol (TC), high density lipoprotein (HDL), Low density lipoprotein cholesterol (LDL-C), malondialdehyde (MDA), superoxide dismutase (SOD), reduced glutathione (GSH) and vascular cell adhesion molecule 1 (VCAM- 1) were estimated. Lung specimens were prepared and stained with H&E, Masson trichrome and immunehistochemical stains for assessment of transforming growth factor beta 1 (TGF-β1) and Bax. Morphometric study followed by statistical analysis were done. Results: NIC group showed elevation in serum levels of total protein, TC, LDL-C, TGs, MDA and VCAM-1 with evident diminishing in the serum levels of HDL-C, SOD, and GSH. Apoptosis and damage of alveolar epithelium and bronchiolar cells, marked fibrosis, inflammatory cell infiltrate and congestion of blood vessels were observed. Marked increase in the mean alveolar wall thickness, mean area% of collagen fibers deposition, mean area% of TGFβ1 immuno-expression and mean number of Bax immune positive cells while a decrease in the mean linear intercept were detected. AG co-administered with nicotine ameliorated these biochemical, histopathological and morphometric changes. Conclusion: AG ameliorates NIC induced lung damage in rats through improving the biochemical parameters and by decreasing TGF-s1 and Bax immunoexpression.

VCAM-1 and ICAM-1 Serum Levels as Markers of Relapse in Visceral Leishmaniasis.

Objectives-Methods. Visceral leishmaniasis (VL) is characterized by chronicity and relapses despite efficacious treatment. Acute and chronic inflammatory processes and concomitant disturbances in cell adhesion characterize the pathogenesis of the disease. To investigate these processes further we measured adhesion molecules (L-selectin, ICAM-1 and VCAM-1) serum levels in 16 children with VL, as well as in 20 healthy controls. All children were treated with liposomal amphotericin B (3 mg/kg) on days 1 to 5, 14, and 21. Measurements were performed at days 0, 15 and 30. Results. All children responded well to treatment in both clinical and laboratory terms. In three cases relapse occurred at 3, 5 and 6 months after treatment had ended. Serum L-selectin levels, both pre-treatment and post-treatment, did not significantly differ between patients and controls. VCAM-1 and ICAM-1 median levels were similar in patients and controls (P&gt;0.05) at day 0 and significantly increased at day 15 (P&lt;0.05). Interestingly, VCAM-1 and ICAM-1 dropped at day 30, with median levels comparable to those before treatment in the 13 children who subsequently had a good outcome without relapses (P&gt;0.05), but not in the 3 patients who relapsed (P&lt;0.05). Conclusions. Despite the small number of the patients, the changes in VCAM-1 and ICAM-1 levels indicate the anti-parasite activation of the immune system during the course of VL and the effect of treatment. Decline in post-treatment serum VCAM-1 and ICAM-1 levels might be used as a marker of treatment efficacy in childhood VL.

Role of several cytokines and adhesion molecules in the diagnosis and prediction of survival of hepatocellular carcinoma

Background and study aimsThere is still need for accurate markers for early diagnosis of hepatocellular carcinoma (HCC) and assessment of prognosis. The aim of this study is to investigate interleukin (IL)-32, IL-1 beta, IL-18, vascular cell adhesion molecule (VCAM)-1, and epithelial cell adhesion molecule (EpCAM) in the diagnosis and assessment of prognosis of HCC. Patients and methodsFifty patients with HCC and 15 healthy volunteers were enroled into this prospective study. Serum samples were obtained at the first admission before any treatment was given. Serum IL-32, IL-1 beta, IL-18, VCAM-1, and EpCAM levels were determined using ELISA kits. ResultsThe mean age of the patient group and controls was 60±9years and 56±8years, respectively. The mean serum level of IL-32 was higher in patients with HCC than in the control subjects (65.1 vs. 14.1pg/mL; p<0.001). IL-18 levels were significantly higher in the HCC group (546.5 vs. 157.8pg/mL; p<0.001). EpCAM (20.3 vs. 1.5pg/mL; p<0.001) and VCAM (6.5 vs. 1.8μg/mL; p<0.001) levels were also higher in patients with HCC. The mean level of IL-1 beta in the HCC group was similar to that in the control subjects (1.9 vs. 1.9pg/mL; p=0.97). Fifty-eight per cent of the patients with HCC died at 7.3months (median). Cytokine levels except EpCAM did not correlate with survival (p>0.05). Alpha-foetoprotein, IL-32, IL-18, EpCAM, and VCAM had valuable cutoff levels to differentiate between patients with HCC and control group (p<0.001). ConclusionsAlthough cytokines can be a diagnostic marker for HCC, they did not have any significant prognostic value in patients with HCC. Only EpCAM may be used to determine the prognosis of HCC, thereby assisting with treatment management.

Endothelial dysfunction correlates with decompression bubbles in rats.

Previous studies have documented that decompression led to endothelial dysfunction with controversial results. This study aimed to clarify the relationship between endothelial dysfunction, bubble formation and decompression rate. Rats were subjected to simulated air dives with one of four decompression rates: one slow and three rapid. Bubble formation was detected ultrasonically following decompression for two hours, before measurement of endothelial related indices. Bubbles were found in only rapid-decompressed rats and the amount correlated with decompression rate with significant variability. Serum levels of ET-1, 6-keto-PGF1α, ICAM-1, VCAM-1 and MDA, lung Wet/Dry weight ratio and histological score increased, serum NO decreased following rapid decompression. Endothelial-dependent vasodilatation to Ach was reduced in pulmonary artery rings among rapid-decompressed rats. Near all the above changes correlated significantly with bubble amounts. The results suggest that bubbles may be the causative agent of decompression–induced endothelial damage and bubble amount is of clinical significance in assessing decompression stress. Furthermore, serum levels of ET-1 and MDA may serve as sensitive biomarkers with the capacity to indicate endothelial dysfunction and decompression stress following dives.

Improved monitoring of clinical response in Systemic Lupus Erythematosus by longitudinal trend in soluble vascular cell adhesion molecule-1

BackgroundTo determine whether optimal use of serial measurements of serum levels of soluble cell adhesion molecules (CAM) can improve monitoring of disease activity in SLE.MethodsSerum levels of soluble CAM and conventional SLE biomarkers were measured in serial samples (n = 80) from 21 SLE patients during and after flare and correlated in longitudinal analysis with disease activity determined by ECLAM score. Blood samples from a second cohort of 34 SLE patients were subject to flow cytometry to correlate serum biomarkers with B cell subsets.ResultsBy adjusting for the baseline level (at the first visit), delta soluble vascular cell adhesion molecule-1 (sVCAM-1) showed stronger correlation with changes in ECLAM score and improved sensitivity and specificity for identifying SLE responders versus non-responders compared to conventional SLE biomarkers including anti-dsDNA antibody titre and complement C3. Multiple regression analysis identified delta sVCAM-1 as the best marker of SLE clinical response. sVCAM-1 levels were significantly correlated with CD95+CD27+ activated memory B cells, CD95+ plasmablasts and circulating plasma cell numbers in SLE patients.ConclusionSubtracting a baseline level of sVCAM-1 for each individual substantially improved its utility as a biomarker. Delta sVCAM-1 was superior to conventional SLE biomarkers for monitoring changes in disease activity. This suggests that serial monitoring of serum sVCAM-1 trends should be considered in SLE patients to document responses to treatment. We hypothesise that the correlation between activated B cell subsets and circulating plasma cell numbers with soluble VCAM-1 serum levels in SLE may relate to the important role of VCAM-1 in B lymphocyte survival and maturation in bone marrow and secondary lymphoid tissues.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-015-0896-7) contains supplementary material, which is available to authorized users.

Evaluation of the effect of Vaccinium arctostaphylos L. fruit extract on serum inflammatory biomarkers in adult hyperlipidemic patients: a randomized double-blind placebo-controlled clinical trial.

Atherosclerosis is a chronic inflammatory condition. Many pro-inflammatory factors including interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), and adhesion molecules including intercellular adhesion molecule (ICAM-1) and vascular cell adhesion molecule (VCAM-1) are expressed in atherosclerotic lesions. The plants of genus Vaccinium are rich in anthocyanins with anti-inflammatory effects. This study aimed to evaluate the effects of Vaccinium arctostaphylos fruit extract on the serum level of TNF-α, IL-6, ICAM-1, and VCAM-1 in adult patients with mild hyperlipidemia to detect its possible inhibitory effects on progression of atherosclerosis. In a randomized double-blind placebo-controlled clinical trial, eligible hyperlipidemic patients were randomly and equally divided in to two groups of study drug or placebo control to receive either the Vaccinium extract or placebo capsules, respectively, twice daily for four consecutive weeks. Each drug capsule contained 0.8 mg of anthocyanins. Serum levels of TNF-α, IL-6, ICAM-1, and VCAM-1 were measured before and after the interventions and finally were compared.A total of 8 men and 12 women in drug group as well as 11 men and 9 women in placebo group completed the study (P = 0.527). The use of Vaccinium extract significantly reduced only the IL-6 level (P = 0.037); however, this reduction was not significant compared to placebo (P = 0.062). Consumption of Vaccinium arctostaphylos fruit extract with the dose of 500 mg twice daily did not show any significant effect on serum levels of TNF-α, IL-6, ICAM-1, and VCAM-1 in adult hyperlipidemic patients. However, considering slight decrease in the level of IL-6, ICAM-1, and VCAM-1, the use of higher doses with longer duration might have significant effects on these factors.

Significance of TNF-α and the Adhesion Molecules: L-Selectin and VCAM-1 in Papillary Thyroid Carcinoma.

Circulating levels of TNF-α and the adhesion molecules L-Selectin and VCAM-1 as well as their expression in the primary tumors of patients with benign thyroid diseases and papillary thyroid carcinoma (PTC) have been determined in this study. The serum levels of TNF-α, L-Selectin, and VCAM-1 were significantly higher in patients with both benign thyroid diseases and PTC as compared to the healthy individuals. However, the levels of only TNF-α and L-Selectin, and not VCAM-1, were significantly higher in patients with PTC in comparison to those observed in patients with benign thyroid diseases. Further the expression of TNF-α and L-Selectin was also significantly higher in the primary tumors of PTC patients, relative to the benign thyroid diseases. The expression of L-Selectin and VCAM-1 significantly correlated with aggressive tumor behavior. In PTC patients, the circulating TNF-α levels significantly positively correlated with the levels of L-Selectin, while TNF-α immunoreactivity was significantly associated with VCAM-1 expression. Serum TNF-α was found to be a significant prognosticator for OS in PTC patients. Overall the results signify that the interaction between TNF-α and the adhesion molecules may have a role in thyroid carcinogenesis and understanding this complexity may offer potential therapeutic targets for better management of thyroid cancer.

Chronic exposure to biomass fuel smoke and markers of endothelial inflammation.

Indoor smoke exposure may affect cardiovascular disease (CVD) risk via lung-mediated inflammation, oxidative stress, and endothelial inflammation. We sought to explore the association between indoor smoke exposure from burning biomass fuels and a selected group of markers for endothelial inflammation. We compared serum concentrations of amyloid A protein, E-selectin, soluble intercellular adhesion molecule 1 (ICAM-1) and VCAM-1, von Willebrand factor (vWF), and high-sensitivity C-reactive protein (hs-CRP) in 228 biomass-exposed vs. 228 non-exposed participants living in Puno, Peru. Average age was 56years (s.d.=13), average BMI was 26.5kg/m(2) (s.d.=4.4), 48% were male, 59.4% completed high school, and 2% reported a physician diagnosis of CVD. In unadjusted analysis, serum levels of soluble ICAM-1 (330 vs. 302ng/ml; P<0.001), soluble VCAM-1 (403 vs. 362ng/ml; P<0.001), and E-selectin (54.2 vs. 52.7ng/ml; P=0.05) were increased in biomass-exposed vs. non-exposed participants, respectively, whereas serum levels of vWF (1148 vs. 1311mU/ml; P<0.001) and hs-CRP (2.56 vs. 3.12 mg/l; P<0.001) were decreased, respectively. In adjusted analyses, chronic exposure to biomass fuels remained positively associated with serum levels of soluble ICAM-1 (P=0.03) and VCAM-1 (P=0.05) and E-selectin (P=0.05), and remained negatively associated with serum levels of vWF (P=0.02) and hs-CRP (P<0.001). Daily exposure to biomass fuel smoke was associated with important differences in specific biomarkers of endothelial inflammation and may help explain accelerated atherosclerosis among those who are chronically exposed.

Etrolizumab Treatment Does Not Modify Levels of VCAM-1 in Ulcerative Colitis Patients

Introduction: Etrolizumab, an anti-β7 mAb, targets the integrins α4β7 and αEβ7 and inhibits the interaction of α4β7 with MAdCAM-1 and VCAM-1, and αEβ7 with E-cadherin. IBD patients have higher expression levels of MAdCAM-1 and ICAM-1 in the gut tissue compared to controls. Expression levels of VCAM-1 (Jones et al., 1995; Panes et al., 2003), an adhesion molecule involved in cell trafficking across the blood-brain barrier, are reported to be similar between IBD patients and controls. We demonstrated that etrolizumab treatment in patients with moderate-to-severe ulcerative colitis (UC) modulates MAd-CAM-1 and E-cadherin in serum and colonic tissue (Vermeire et al., 2012; Fuh et al., 2015; unpublished data) whereas natalizumab has been shown to decrease serum VCAM-1 in multiple sclerosis patients (Millonig et al., 2010). We explored the role of etrolizumab treatment on VCAM-1 and ICAM-1 serum levels and expression in colonic tissue among patients in the Phase 2 EUCALYPTUS study. Methods: Phase 2 UC patients were randomized into 1 of 3 different treatment arms during an induction period of 10 weeks: placebo (n=36), etrolizumab 100mg (n=28), and etrolizumab 300mg (n=34). Soluble VCAM-1 and ICAM-1 were measured at baseline and during the treatment period using commercially available ELISA assays and tissue expression was assessed in biopsy tissue by qPCR. Results: No differences were observed in serum soluble VCAM-1 levels in the etrolizumab- or placebotreated arms, nor was an association found with clinical remission or response. Similar results were observed in VCAM-1 expression in colonic tissue on day 43 and day 71. There was no dose-related decrease of ICAM-1 expression in serum or colonic tissue in the treated arms. However, levels of expression in colonic tissue of clinical responders, in both etrolizumab and placebo treated arms, had a median reduction of ≥50% at day 43 that was maintained through day 71. Conclusion: Lack of changes in VCAM-1 levels in both colonic tissue and in serum is consistent with the mechanism of action of etrolizumab, which does not block interaction of α4β1 with VCAM-1. The observed downmodulation of ICAM-1 expression is likely due to a decrease in tissue inflammation and not direct targeting of the pathway. These and prior data indicate that etrolizumab modulates expression of gut-specific MAdCAM-1 and suggests that it does not affect lymphocyte trafficking to the CNS via VCAM-1 modulation. Funded by Genentech.

The effect of angiotensin-converting enzyme inhibition on inflammatory and angiogenic factors in hypercholesterolemia

Renin-angiotensin system (RAS) can be activated during hyperlipidemia. Angiotensin II increases the migration of monocytes, cytokine levels, and gene expressions of VEGF and VCAM-1. With this in mind, the present work attempted to investigate the effect of angiotensin-converting enzyme (ACE) inhibition on VEGF, VCAM-1, and nitric oxide (NO) serum levels in hypercholesterolemic rats. Forty male Wistar rats were divided into 4 groups including normal diet+saline injection (control), hypercholesterol diet+saline injection, normal diet+captopril injection, and hypercholesterol diet+captopril injection. Before and after the beginning of the diet and after the treatment, the serum levels of cholesterol, triglycerides, LDL, HDL, and NO were measured. Finally, gene expressions of VCAM-1 and VEGF in the vascular cells from aorta were determined. Hypercholesterolemic diet increased the serum levels of cholesterol, LDL (p<0.001), triglycerides (p<0.01) and decreased HDL (p<0.001). Captopril caused a reduction in the serum levels of cholesterol, LDL (p<0.001), and triglycerides (p<0.05) as well as an increase in HDL levels (p<0.01). Although the serum levels of NO decreased after hypercholesterolemic diet (p<0.001), no significant change was observed after the treatment. Increased gene expressions of VEGF (p<0.05) and VCAM-1 (p<0.01) in hypercholesterolemia were regressed in captopril treated rats (p<0.01 and p<0.05, respectively). Captopril, an ACE inhibitor, improves hyperlipidemia and prevents from overexpression of genes for VEGF and VCAM-1, that are implicated in the inflammation and angiogenesis.