Serum Vascular Cell Adhesion Molecule-1 Research Articles

Homocysteine Impairs Endothelial Cell Barrier Function and Angiogenic Potential via the Progranulin/EphA2 Pathway.

Hyperhomocysteinemia is a well-recognized independent risk factor for cardiovascular disease. To date, the mechanism of pathological plasma homocysteine (Hcy) level elevation remains to be elucidated. We aimed to investigate the levels of progranulin (PGRN), Eph-receptor tyrosine kinase-type A2 (EphA2), vascular cell adhesion molecule-1 (VCAM-1), and Hcy in patients with arteriosclerosis and investigate their functions in Hcy-injured human umbilical vein endothelial cells (HUVECs). EphA2 knockdown was induced in HUVECs by shRNA lentivirus infection with EphA2-RNAi, and bulk RNA-seq assay was performed. Then we investigated the mechanism underlying the effect of recombinant human PGRN (rhPGRN) combined with shRNA interference of EphA2 on cell proliferation, migration, and angiogenesis in Hcy-injured HUVECs. Results showed that serum EphA2, VCAM-1, and Hcy levels in acute coronary syndrome patients were significantly higher than those in chronic coronary syndrome patients (p = 0.000; p = 0.000; p = 0.033, respectively). In vitro, we demonstrated that knockdown of EphA2 significantly impaired cell adhesion and inhibited HUVECs migration and angiogenesis (p < 0.001), which was associated with reduction in VCAM1 and VE-cadherin (p < 0.05). Hcy modulated the expression of PGRN and EphA2 in a time-and dose-dependent manner. However, rhPGRN ameliorated the Hcy-induced reduction in cell viability and migration (p < 0.05). Mechanistically, we found that PGRN/EphA2 and its downstream AKT/NF-κB signaling might be the primary signal transduction pathways underlying Hcy-induced injury. The present study illustrated that PGRN plays a previously unrecognized role in Hcy-induced endothelial injury, which is achieved through its interaction with EphA2 signaling, implying a promising therapeutic target for cardiovascular disease.

The relationship between serum VCAM-1 level and lupus nephritis in patients with systemic lupus erythematosus

Introduction: Nephritis is a frequent inflammatory autoimmune complication in systemic lupus erythematosus (SLE). Detecting the nephritis state of SLE patients using non-invasive biomarkers seems to be necessary. Objectives: This study aimed to evaluate role of vascular cell adhesion molecule-1 (VCAM-1) as a noninvasive method in the assessment of lupus nephritis. Patients and Methods: This study was conducted at Imam Reza hospital in Mashhad, Iran, during 2017-2018. A total of 114 SLE patients diagnosed based on the lupus diagnosis criteria including the clinical and paraclinical symptoms that were referred to the rheumatology or nephrology clinics and were enrolled in the study. After obtaining informed consent, a blood sample was taken to determine serum VCAM-1 levels. All patients were evaluated for glomerular hematuria and proteinuria in addition to testing for serum C3, and C4, anti-nuclear antibody (ANA) and anti-ds DNA levels. The serum urea and creatinine levels as well as 24-hour urine protein were measured. Finally, the patients were designed into two groups of SLE with and without nephritis. A renal biopsy was performed in lupus patients with nephritis to determine the class of the disease. The association between serum levels of VCAM-1 and activity of SLE disease [systemic lupus erythematosus disease activity index (SLEDAI)], anti-dsDNA serum level, glomerular hematuria, proteinuria, and lupus nephritis class were evaluated. Results: According to statistical analysis there was no significant relationship between SLEDAI and VCAM-1 levels was detected (P&gt;0.05). Additionally, no significant relationship between VCAM-1 levels and lupus nephritis classes was detected (P&gt;0.05); however the serum VCAM-1 levels were significantly lower in patients with hematuria (P= 0.021). Conclusion: There is no correlation between serum VCAM-1 levels and classes of lupus nephritis. Our data however requires further investigation on its clinical implications.

The Relationship Between Serum VCAM-1 and Alzheimer's Disease in Patients with Type 2 Diabetes Mellitus.

BackgroundPrevious studies have reported that diabetes mellitus (DM) is a risk factor for Alzheimer’s disease (AD). Vascular cell adhesion molecule-1 (VCAM-1) plays an important role in the pathological process of atherosclerosis. The aim was to elucidate the relationship between serum VCAM-1 and early AD in DM patients.MethodsSerum samples for VCAM-1 were tested in 208 DM patients. All included DM patients were followed up for a median of 36 months prospectively. The prognostic value of serum VCAM-1 for predicting AD events was analyzed by using Cox proportional hazard.ResultsSerum VCAM-1 was independently associated with AD history after adjusting for related confounding factors in patients with DM at baseline by using the logistic regression analysis (OR=1.861; 95% CI, 1.435–2.539; Ptrend=0.020). The Cox proportional hazard model suggested that VCAM-1 was a prognostic factor for AD events in the DM patients (HR=2.728; 95% CI, 1.785–5.439; Ptrend<0.001). Stratified analysis showed that the significant association between AD event and serum VCAM-1 in DM patients was not affective by CVD history.ConclusionOur results showed that higher VCAM-1 levels were significantly related to a higher risk of AD events in DM patients. The serum biomarker might be beneficial to predict AD early. Serum VCAM-1 might be a good biochemical parameter for predicting AD in DM.

Trihoney Suppresses Soluble Adhesion Molecules (ICAM-1 and VCAM-1 in Hypercholesterolemic Atherosclerotic Rabbits: A Comparative Study with Atorvastatin

Atherosclerosis is a chronic inflammatory disease and high serum cholesterol proven as the main trigger of its pathogenesis. Development of atherosclerotic lesions is closely related to the level of serum cholesterol. Expression of adhesion molecules has been correlated with the extent of aortic lesions. Serum circulating forms of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) have been detected in high levels in vascular inflammatory diseases. Honey has been shown to diminish the expression of VCAM-1 in vascular endothelium. Thirty-six male New Zealand white (NZW) rabbits were grouped into: normal diet (C), normal diet with 0.6 g/kg/ day of Trihoney (C+H), 1% cholesterol diet (HCD), 1% cholesterol diet with 0.3 g/kg/day of Trihoney (HCD+H1), 1% cholesterol diet with 0.6 g/kg/day of Trihoney (HCD+H2) and 1% cholesterol diet with 2 mg/kg/day of atorvastatin (HCD+At). Animals were sacrificed after 12 weeks of treatment. Serum was analysed for lipids, ICAM-1 and VCAM-1. Atherosclerotic plaques in the aorta were quantified. Serum ICAM-1 and VCAM-1 were significantly elevated in the HCD group when compared to the control groups. Groups Supplemented with Trihoney showed a significant suppression of serum ICAM-1 and VCAM-1 in comparison to the HCD group. Serum ICAM-1 and VCAM-1 exhibited a significant positive correlation with serum cholesterol. Serum VCAM-1 showed a significant positive correlation with the percentage of aortic lesions. Results of this study showed that Trihoney has anti-atherosclerotic potential through suppression of adhesion molecules. Trihoney was comparable to atorvastatin and may be suggested as an adjuvant remedy for protection against atherosclerosis.

The effect of coenzyme Q10 supplementation on inflammatory and endothelial dysfunction markers in overweight/obese polycystic ovary syndrome patients

Background This study aimed at determining the effects of coenzyme Q10 (CoQ10) supplementation on the inflammatory and endothelial dysfunction indices among overweight and obese women with polycystic ovary syndrome (PCOS). Methods This randomized double-blind, placebo-controlled clinical trial was performed among overweight and obese women diagnosed with PCOS. Forty three PCOS women were randomly assigned to two groups: one group received 200 mg CoQ10 capsules per day (n = 22) and the other received placebo (n = 21) for 8 weeks. Biomarkers of inflammation and endothelial dysfunction including high sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and E-selectin were measured and compared before and after the intervention. Results At the end of study, compared with pldacebo, CoQ10 supplementation resulted in significant decreases in serum levels of TNF-α (p = 0.009), hs-CRP and IL-6 (p = 0.001, p = 0.007, respectively). In addition, supplementation with CoQ10 resulted in a significant reduction in serum VCAM-1 (p = .002) and E-selectin (p = .006) compared with the control group. There were no significant differences for serum ICAM-1. Conclusions The present study showed that CoQ10 supplementation for 8 weeks had a beneficial effect on inflammatory and endothelial dysfunction markers in overweight and obese patients with PCOS.

First trimester inflammatory mediators in women with chronic hypertension.

Chronic hypertension complicates 1%-2% of pregnancies and is one of the most significant risk factors for the development of preeclampsia. Inflammatory mediators, such as interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), vascular cell adhesion molecule (VCAM) and endothelin have been implicated in the endothelial dysfunction that is pathognomonic of preeclampsia and may serve as useful first trimester biomarkers for the prediction of preeclampsia. The objectives of this study are: first, to investigate differences in serum levels of IL-6, TNF-α, VCAM and endothelin at 11+0 to 13+6 weeks' gestation in women with chronic hypertension who developed superimposed preeclampsia with those who did not and normotensive controls and, second, to evaluate the performance of these biomarkers in the prediction of preeclampsia. The study population was comprised of 650 women with chronic hypertension, including 202 who developed superimposed preeclampsia and 448 who did not, and 142 normotensive controls matched to the chronic hypertension group for storage time and racial origin. Serum concentrations of IL-6, TNF-α, VCAM and endothelin were measured and the values were converted into multiples of the expected median using multivariate regression analysis in the control group. The multiples of the median values of the biomarkers between the two groups of women with chronic hypertension and the controls were compared, and the receiver operating characteristic curve (ROC) was used to assess the performance of these variables for the prediction of preeclampsia. In women with chronic hypertension, compared with the normotensive controls, there was a significantly higher first trimester median concentration of endothelin but not of VCAM, IL-6 or TNF-α. Within the cohort of women with chronic hypertension, those who developed superimposed preeclampsia, compared with those who did not, had higher first trimester serum concentration of VCAM but not of endothelin, IL-6 or TNF-α. However, serum VCAM provided a poor prediction of superimposed preeclampsia (area under the ROC curve 0.537, 95% CI 0.487-0.587). Women with chronic hypertension have increased serum endothelin in the first trimester of pregnancy and those who develop superimposed preeclampsia have higher levels of VCAM. None of the inflammatory mediators performed well in the first trimester in the prediction of preeclampsia.

Expression and pathogenesis of VCAM-1 and VLA-4 cytokines in multiple myeloma.

ObjectiveThe objective of this study is to investigate the expression of Vascular cell adhesion molecule-1 (VCAM-1) and very late appearing antigen-4 (VLA-4) cytokines in MM (multiple Myeloma).MethodForty patients with MM are selected as the experimental group and 30 healthy persons as the control group. Flow cytometry is used to detect the expression of VCAM-1 (CD106), VLA-4 (CD49d), CD38 and CD138 antigens in experimental group and control group. ELISA (Enzyme Linked Immunosorbent Assay) is used to detect the concentration of VCAM-1 in serum of experimental group and control group. RT-PCR is used to detect the expression of VCAM-1.ResultsThe positive rate and antigen expression rate of VACM-1 antigen in the experimental group were significantly higher than those in the control group (P < 0.05). There were statistical differences of VLA-4 and VCAM-1 antigens between the initial diagnosis group and the relapse/refractory group, and between the relapse/refractory group and the platform stage group (P < 0.05). There were significant differences between VLA-4 antigen and VACM-1 antigen, phase I and phase II, and between phase I and phase III (P < 0.05). The concentration of VCAM-1 and the expression of VCAM-1 mRNA in the experimental group were significantly higher than (P < 0.01). In the different stages of ISS (International Staging System) and different disease groups in the experimental group, the concentration of VCAM-1 and the expression level of VCAM-1 mRNA are significantly different among the three groups of stage I, II and III (P < 0.01). There is a significant difference between the initial diagnosis group, the relapse/refractory group and the platform group (P < 0.05).ConclusionThere are abnormal expressions of adhesion molecules VCAM-1 and VLA-4 in multiple myeloma patients, which are related to ISS staging.

Protective Effects of Biscoclaurine Alkaloids on Leukopenia Induced by 60Co-γ Radiation.

Objective Leukopenia, a common complication of tumor chemoradiotherapy, contributes serious damage to the hematopoietic, gastrointestinal, and immune systems of the body and can cause delay, discontinuation, or even failure to tumor treatment, thereby greatly threatening human health. The present study aims to investigate the protective effects of biscoclaurine alkaloids (BA) on leukopenia. Methods This study was conducted on 60 Kunming mice, which were randomly divided into six groups containing 10 animals each. A hematology analyzer was used to count white blood cells (WBC) in the peripheral blood cell. Mice serum was collected, and the granulocyte-macrophage colony-stimulating factor, vascular cell adhesion molecule 1 (VCAM-1), and interferon-γ (IFN-γ) were detected by enzyme-linked immunosorbent assays. Pathological changes were detected through hematoxylin and eosin staining in the liver and spleen of mice. The spleen and liver ultrastructures were observed via electron microscopy. Results Results showed that BA ameliorated WBC, PLT reduction in the peripheral blood and significantly increased the levels of IFN-γ and VCAM-1 in mice serum. BA reduced ionizing radiation-induced injuries to spleen, mitigated the reduction of superoxide dismutase (SOD), and significantly decreased the malonaldehyde (MDA) and xanthine oxidase (XOD) levels in the liver. Conclusion BA enhanced the immune and hematopoietic functions and ameliorated the oxidative stress induced by 60Co-γ radiation, revealing its therapeutic potential both as a radioprotector and as a radiation mitigator for leukopenia induced by 60Co-γ radiation.

Inflammation inhibition and gut microbiota regulation by TSG to combat atherosclerosis in ApoE-/- mice.

2,3,5,4'-Tetrahydroxy-stilbene-2-O-β-D-glucoside (TSG) is the main active component of Polygoni Multiflori Radix, a root of the homonymous plant widely used in traditional Chinese medicine. TSG has protective effects on the liver, reduces cholesterol and possesses anti-oxidant, anti-tumor, and anti-atherosclerotic properties. However, the pharmacological effects and mechanisms of action of Polygonum multiflorum on atherosclerosis (AS) have not been studied yet. The aim of this research was to study the effects of Polygoni Multiflori Radix Praeparata (PMRP) and its major active chemical constituent TSG on AS in ApoE-deficient (ApoE-/-) mice fed with high fat diets to provide a scientific basis in the use of PMRP and TSG against cardiovascular diseases. High fat diet induced AS in ApoE-/- mice were treated with PMRP, TSG (low and high doses), and simvastatin (SIM) for 8 weeks. At the end of the treatment, mouse serum lipid levels, triglycerides (TG), and total cholesterol (TC) were measured by an oxidase method (other indicators were determined by ELISA), while the content in oxidized low density lipoprotein (ox-LDL) and the expression of inflammatory factors such as interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), vascular cell adhesion molecule-1 (VCAM-1), and monocyte chemotactic protein-1 (MCP-1) in the serum and aortic samples were measured by ELISA. Atherosclerotic plaque morphology was evaluated by oil red O in thoracic aorta. In addition, 16S rDNA-V4 hypervariable region genome sequence of all microbes in the fecal sample from each group was analyzed to evaluate potential structure changes in the gut microbiota after treatment with PMRP and TSG. TSG markedly inhibited AS plaque formation in ApoE-/- mice. Furthermore, PMRP and TSG improved lipid accumulation by reducing TG and ox-LDL levels. TSG inhibited inflammation by the down-regulation of IL-6, TNF-α, VCAM-1 and MCP-1 expression in serum, and PMRP inhibited inflammation by reducing VCAM-1, ICAM-1 and CCRA expression in aortic tissue. In addition, TSG reduced or prevented AS by the regulation of the composition of the overall gut microbiota, such as Firmicutes, Bacteroidetes, Tenericutes, Proteobacteria phyla, Akkermensia genera and Helicobacter pylori. PMRP and TSG improved lipid accumulation and inflammation, and regulated the intestinal microbial imbalance in ApoE-/- mice. TSG exerted a preventive effect in the development and progression of AS.

Effects of budesonide nasal spray and ebastine combined with Xinqin granule on symptom improvement and serum T cell subsets and vascular cell adhesion molecule-1(VCAM-1) levels in patients with allergic rhinitis

Objective To investigate the effect of budesonide nasal spray and ebastine combined with Xinqin granule on symptom improvement and serum T cell subsets and vascular cell adhesion molecule-1(VCAM-1) levels in patients with allergic rhinitis. Methods From February 2015 to April 2017, 107 cases of allergic rhinitis in Yuncheng Central Hospital were divided into two groups according to the different ways of treatment.Fifty-three cases in the control group were treated with budesonide nasal spray and ebastine, 54 cases in the study group were treated with Xinqin granule based on the control group.The improvement of nasal congestion, sneezing, runny nose, nasal itching symptom score and serum VCAM-1, T cell subsets (CD3＋, CD4＋, CD19＋) levels of the two groups were analyzed and compared before treatment and after half a month of the treatment.The clinical effect and incidence of adverse reactions were compared between the two groups. Results After treatment for half a month, the nasal congestion, sneezing, runny nose, nasal itching symptom scores of the study group were lower than those of the control group(all P<0.05). The clinical effect of the study group[87.04%(47/54)] was higher than that of the control group[67.92%(31/53), χ2=2.970, P<0.05]. After treatment for half a month, the serum VCAM-1, CD3＋, CD4＋ and CD19＋ levels in the study group were better than those in the control group[(572.26±120.67)ng/L vs.(864.87±238.56)ng/L, (68.69±3.31)% vs.(72.08±4.29)%, (39.79±3.28)% vs.(44.61±4.78)%, (10.79±1.64)% vs.(13.61±2.18)%](all P<0.05). The incidence rate of adverse reactions in the study group was 11.11%(6/54). which in the control group was 5.66%(3/53), the difference was not statistically significant (χ2=0.445, P=0.504). Conclusion Budesonide nasal spray and ebastine combined with Xinqin granule in the treatment of patients with allergic rhinitis has significant effect.It can significantly improve the levels of serum VCAM-1 and T cell subsets with high security. Key words: Rhinitis, allergic, perennial; Budesonide; Ebastine; Xinqin granule; Treatment outcome

Intercellular adhesion molecule-1 (ICAM-1) associates with 24-hour ambulatory blood pressure variability in type 2 diabetes and controls

Background and aimEndothelial dysfunction is a common feature in hypertension and type 2 diabetes. Whether blood pressure (BP) variability is influencing serum intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) remains to be clarified. We aimed to assess the association between the circulating adhesion molecules and ambulatory blood pressure variability in patients with type 2 diabetes and controls. Patients and methodsThe study included data from type 2 diabetes with controlled BP (n = 55), type 2 diabetes with uncontrolled BP (n = 55) and control subjects (n = 28). ICAM-1 and VCAM-1 were measured with specific enzyme–linked immunosorbent assay method. BP variability was assessed using standard deviation of mean systolic and diastolic BP evaluated during 24-hour ambulatory BP monitoring. ResultsThe uncontrolled BP type 2 diabetes group had significantly higher serum ICAM-1 and VCAM-1 levels compared to controlled BP type 2 diabetes and control groups. In linear regression analysis, after adjustment, higher ICAM-1 was consistently associated with higher daytime and 24-hour diastolic BP variability, and daytime systolic BP variability in the study population. VCAM-1 was associated only with daytime systolic BP variability. ConclusionsOur study evaluating the association of serum ICAM-1 and VCAM-1 with 24-hour ambulatory BP variability in patients with type 2 diabetes and controls might offer better understanding of the mechanisms generating endothelial dysfunction. Elevated 24-hour ambulatory BP variability might induce endothelial activation by increasing circulating adhesion molecules levels.

Tocotrienol-rich vitamin E improves diabetic nephropathy and persists 6-9 months after washout: a phase IIa randomized controlled trial.

Chronic hyperglycemia in type 2 diabetes mellitus increases oxidative stress and inflammation which contributes to long-term diabetic kidney disease. Tocotrienol-rich vitamin E, as Tocovid, has been shown to reduce oxidative stress and inflammation to ameliorate diabetes in rat models and human subjects. In this prospective, multicenter, double-blinded, placebo-controlled clinical trial, 54 patients (duration = 18.4 years, HbA1c = 8.8%) with diabetic nephropathy were randomized to receive Tocovid 200 mg or placebo for 12 weeks. Fasting blood samples were taken to measure HbA1c, serum creatinine, estimate glomerular filtration rate (eGFR), urine albumin:creatinine ratio, malondialdehyde, tumor necrosis factor receptor-1, vascular cell adhesion molecule-1 (VCAM-1), and thromboxane-B2. Patients were reassessed 6–9 months post-washout. After 12 weeks of supplementation, Tocovid significantly decreased serum creatinine levels (mean difference: –3.3 ± 12.6 versus 5.4 ± 14.2, p = 0.027) and significantly increase eGFR (mean difference: 1.5 ± 7.6 versus –2.9 ± 8.0, p = 0.045) compared with placebo. There were no significant changes in HbA1c, blood pressure, and other parameters. Subgroup analysis revealed that in patients with low serum vitamin E concentrations at baseline, Tocovid reduced serum creatinine, eGFR, and VCAM-1 significantly. After 6–9 months of washout, persistent difference in serum creatinine remained between groups (mean difference: 0.82 ± 8.33 versus 11.26 ± 15.47, p = 0.031), but not eGFR. Tocovid at 400 mg/day significantly improved renal function in 12 weeks of supplementation, as assessed by serum creatinine and eGFR, which remained significant 6–9 months post-washout.

EVALUATION OF THE INTERRELATIONS OF BLOOD VCAM-1 LEVEL AND CLINICO-MORPHOLOGICAL CHARACTERISTICS OF CHRONIC GLOMERULONEFRITIS

Chronic glomerulonephritis is characterized by irreversible progression of the pathological process, which leads to the formation of terminal renal failure significantly impairing the patient's quality of life, leading to internal dysfunction and increasing the risk of premature overall and cardiovascular mortality. Consequently, the search for non-invasive methods for assessing the state of renal tissue, including the detection of proteins involved in renal inflammation, fibrosis, intercellular interaction is currently important.THE AIM: To determine the serum levels of the vascular cell adhesion molecule-1 (VCAM-1) in patients with various forms of chronic glomerulonephritis (CGN) and to clarify its relationship to the development of morphological changes in the renal tissue.PATIENTS AND METHODS: In 80 patients (men and women), with CGN in the acute stage was carried out a detailed clinical and laboratory examination, including determination of serum VCAM-1 by ELISA and performing puncture renal biopsy with the assessment of morphological changes. Statistical analysis of the results was carried out using «Microsoft Office Excel 2010» («Microsoft Corp.», USA) and "STATISTICA 10.0" («StatSoft Inc.», USA).RESULTS. The serum level concentration of VCAM-1 was 719 [643;771] ng/ml. Obtained statistically significant interrelations with enlargement of mesangial space, endothelial growth, capillary walls thickening, mesangial hypercellularity, endothelial hypercellularity, protein casts in tubules, anses capillaries union, fibrose demilunes, podocyte necrosis, hypertrophic remodeling type of resistive type vessels, Ig deposites, IgA deposites, IgG seposites, C3 complement fluorescence, fibrinogen deposites. CONCLUSION: The results of the study demonstrate the important role of VCAM-1 in the development of immunocomplex inflammation in glomerulonephritis. VCAM-1 is a marker of different morphological changes in CGN, and determining the level of VCAM-1 in serum is informative, simple and noninvasive method which provides evaluation of inflammatory process activity, prediction of the risk of morphological changes in the renal tissue structure in patients with CGN.

Galectin-3 Interacts with Vascular Cell Adhesion Molecule-1 to Increase Cardiovascular Mortality in Hemodialysis Patients.

Background: Interactions and joint effects of galectin-3 and vascular cell adhesion molecule 1 (VCAM-1) on risks of all-cause and cardiovascular (CV) mortality remain unclear in patients with maintenance hemodialysis (MHD). Methods: Unadjusted and adjusted hazard ratios (aHRs) of mortality risks were analyzed between higher and lower concentration groups of serum galectin-3 and VCAM-1. The modification effect between serum galectin-3 and VCAM-1 on mortality risk was investigated using an interaction product term. Results: During follow-up, galectin-3 and VCAM-1 were associated with incremental risks of all-cause mortality (aHR: 1.038 (95% confidence interval (CI): 1.001–1.077) and 1.002 (95% CI: 1.001–1.003), respectively). Nonetheless, VCAM-1 but not galectin-3 predicted CV mortality (aHR: 1.043 (95% CI: 0.993–1.096) and 1.002 (95% CI: 1.001–1.003), respectively). In the interaction analysis, patients with combined higher galectin-3 (>29.5 ng/mL) and VCAM-1 (>1546.9 ng/mL) were at the greatest risk of all-cause and CV mortality (aHR: 4.6 (95% CI: 1.6–13.4), and 4.2 (95% CI: 1.3–14.4), respectively). The interactions between galectin-3 and VCAM-1 with respect to all-cause and CV mortality were statistically significant (p < 0.01 and < 0.05, respectively). Conclusion: Galectin-3 and VCAM-1 could serve as a promising dual biomarker for prognostic assessment, considering their joint effects on pathogenesis of leukocyte trafficking and atherothrombosis.

Lower serum kallistatin level is associated with 28-day mortality in patients with septic shock

PurposeInvestigation for whether serum levels of kallistatin, vascular cell adhesion molecule-1 (VCAM-1), and E-selectin are associated with outcomes in patients with septic shock Material and methodsBiomarker levels were measured using blood samples from patients with septic shock at admission, 24 h, and 72 h and from healthy volunteers. The primary outcome was 28-day mortality. ResultsFifty-eight survivors, fourteen non-survivors, and six healthy volunteers were enrolled. Serum kallistatin level was lower and serum VCAM-1 and E-selectin levels were higher in patients at admission compared with healthy volunteers. Serum kallistatin levels were higher in survivors compared with non-survivors at all time points (4.4 μg/mL [2.9–6.1] vs. 2.5 μg/mL [2.1–5.0], P = 0.019 at admission; 4.3 μg/mL [3.3–5.2] vs. 3.2 μg/mL [2.2–3.8], P = 0.004 at 24 h; 3.1 μg/mL [2.5–4.2] vs. 2.3 μg/mL [1.7–3.1], P = 0.012 at 72 h), while VCAM-1 and E-selectin levels showed no difference. In the multivariable analysis, serum kallistatin level at 24 h was independently associated with 28-day mortality (OR, 0.29; 95% CI, 0.08–0.69, P = 0.024). ConclusionsLower serum kallistatin level at 24 h was independently associated with 28-day mortality in patients with septic shock

Relationship between serum vascular cell adhesion molecule-1 and endothelin-1 levels with organ involvement and disease activity in systemic lupus erythematosus patients.

Background Endothelial dysfunction plays an important role in pathogenesis of systemic lupus erythematosus (SLE). Considering the importance of serum soluble vascular cell adhesion molecule-1 as the most abundant of the circulating adhesion molecules increased as a result of endothelial dysfunction and the role of endothelin-1 in pathophysiology of SLE, this study aimed to evaluate serum soluble vascular cell adhesion molecule-1 and endothelin-1 levels in SLE patients compared to healthy subjects. Methods In this cross-sectional study, 60 SLE patients according to the Systemic Lupus International Collaborating Clinics classification criteria for SLE and 40 age and sex-matched healthy controls were included. In patients, clinical examination was performed and SLE disease activity index was assessed. Serum endothelin-1 and soluble vascular cell adhesion molecule-1 levels were measured using ELISA kits. Results The mean ± standard deviation age of patients and controls was 31.91 ± 7.66 and 33.20 ± 10.08 years, respectively. Compared to healthy controls, serum soluble vascular cell adhesion molecule-1 (1023.8 ± 352.96 vs. 866.06 ± 109.91) and endothelin-1 (77.83 ± 16.27 vs. 54.45 ± 12.01) was significantly higher in SLE patients ( P = 0.003 and P < 0.001, respectively). The most common organs involved in patients were skin, joint and kidney. There were no significant differences in serum soluble vascular cell adhesion molecule-1 and endothelin-1 levels according to organ involvement, activity of disease and the conventional serum markers of disease activity ( P > 0.05). There was no significant correlation between disease activity, organ involvement and negative or positivity of autoantibodies as well as serum complement with endothelin-1 and vascular cell adhesion molecule-1 levels ( P > 0.05). Conclusions Although our study revealed higher serum soluble vascular cell adhesion molecule-1 and endothelin-1 levels in SLE patients compared to healthy controls, there were no significant correlations between their serum levels with organ involvement and disease activity.

Increased serum levels of adhesion molecules ICAM-1 and VCAM-1 in systemic sclerosis are not specific for pulmonary manifestations.

Studies suggest elevated serum intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) levels may be markers of pulmonary arterial hypertension in systemic sclerosis (SSc-PAH). We sought to evaluate whether ICAM-1 and VCAM-1 levels are useful screening biomarkers for incident SSc-PAH. In this cross-sectional study, four groups were selected from the Australian Scleroderma Cohort Study: group 1 (n = 15) had definite PAH; group 2 (n = 19) had interstitial lung disease (ILD); group 3 (n = 30) were SSc-controls; and group 4 (n = 34) were healthy controls. Serum ICAM-1 and VCAM-1 levels were measured using the Millipore Milliplex MAP Human 2-Plex Panel. There were no differences in ICAM-1 levels in the PAH versus ILD group (263.0 ± 85.4 vs 380.4 ± 168.3ng/mL, p = 0.136), SSc-controls (263.0 ± 85.4 vs 253.1 ± 98.0ng/mL, p = 1.00), or healthy controls (263.0 ± 85.4 vs 201.8 ± 57.2ng/mL, p = 0.093). Similarly, there were no differences in VCAM-1 level in PAH versus ILD groups (1476.2 ± 434.9 vs 1424.8 ± 527.6ng/mL, p = 1.00) and SSc-controls (1476.2 ± 434.9 vs 1409.5 ± 341.1ng/mL, p = 1.00). SSc subjects had significantly higher levels of ICAM-1 (297.4 ± 134.0 vs 201.8 ± 57.2ng/mL, p < 0.0001) and VCAM-1 compared to healthy controls (1432.7 ± 427.4 vs 1125.6 ± 273.4ng/mL, p < 0.0001). Neither ICAM-1 nor VCAM-1 is a specific screening biomarker of SSc-PAH. Instead, increased levels of these adhesion molecules in SSc, irrespective of pulmonary complications, suggest that they may play a role in SSc pathogenesis.

Effect of sildenafil citrate on circulating levels of sFlt-1 in preeclampsia.

To examine the effect of sildenafil on level of antiangiogenic proteins of preeclampsia. Firstly to examine the effect of sildenafil on serum biomarkers in a patient with preterm preeclampsia. Secondly, to examine the effect of sildenafil on sFlt-1 and soluble endoglin secretion from primary trophoblasts and placental explants. The clinical team administered 50 mg tds sildenafil to a 26-year-old primigravid woman with severe preeclampsia at the threshold of viability (24 3/7 weeks gestation) and we collected bloods to examine the effect of slidenafil on antiangiogenic factors sFlt-1 and soluble endoglin (sENG), pro-angiogenic factor PlGF and vascular cell adhesion molecule 1 (VCAM-1) and endothelin-1 (ET1). We administered sildenafil to human primary trophoblasts and placental explants and explored its effect on sFlt-1 and sENG secretion. We examined serum anti-angiogenic factors sFlt-1 and sENG, pro-angiogenic factor PlGF, the potent vasoconstrictor ET1 and VCAM-1 by ELISA. We explored the effect of sildenafil on sFlt-1 secretion from primary trophoblasts and sFlt-1 and sENG secretion from placental explants. We found a reduction in serum sFlt-1, stabilisation in sENG and PlGF in a patient with peri-viable preterm preeclampsia administered oral sildenafil 50 mg three times daily (tds). Furthermore there was an initial stabilisation in serum VCAM-1 and a decline in ET1 with sildenafil administration. This was concordant with stabilisation of clinical and biochemical features of preeclampsia. Interestingly, treating placental cells and tissues in vitro with sildenafil did not appear to change sFlt-1 or sENG secretion. Sildenafil administration was associated with a reduction in serum sFlt-1 and sENG secretion and increase in PlGF secretion in a patient with preterm preeclampsia, potentially via increasing placental perfusion rather than acting directly on the placenta.

The Beneficial Radioprotective Effect of Tomato Seed Oil Against Gamma Radiation–Induced Damage in Male Rats

ABSTRACTRadiation protection research receives intense focus due to its significant impact on human health. The present study was undertaken to investigate the protective effect of pretreatment with tomato seed oil (TSO) against gamma radiation–induced damage in rats. Male Wistar rats were divided into four groups: (1) untreated control; (2) TSO-supplemented; (3) gamma-irradiated; (4) TSO-pretreated and gamma-irradiated. Acute exposure of animals to a single gamma radiation dose (6 Gy) induced oxidative stress in major body organs, altered serum lipid homeostasis, significantly increased serum testosterone and sorbitol dehydrogenase levels, and elicited a systemic inflammation as manifested by the induction of serum vascular cell adhesion molecule-1. Oral pretreatment with TSO (1 ml/kg; 3 times/week for 8 weeks) before exposure to gamma radiation protected rats against ionizing radiation-induced oxidative stress, restored lipid homeostasis, and suppressed systemic inflammation. Histological findings of target tissues verified biochemical data. The radioprotective ability of TSO was attributed to its content of phytosterols, policosanol, and antioxidants, including lycopene, β-carotene, lutein, and tocopherols. TSO is considered a promising radioprotective agent that can be effectively used to protect the body from the damaging effects of harmful radiation.

Relationship between circulating VCAM-1, ICAM-1, E-selectin and MMP9 and the extent of coronary lesions

OBJECTIVES:Inflammatory molecules play a role in the development of atherosclerosis, which is the primary origin of cardiovascular disorders. However, to the best of our knowledge, no study has attempted to investigate the relationship between these circulating molecules and the prediction of cardiovascular risk. The present study aimed to investigate the relationships of vascular cell adhesion molecule-1, intercellular adhesion molecule-1, E-selectin and matrix metalloproteinase 9 serum concentrations with the extent of coronary lesions.METHODS:Seventy-four individuals who were undergoing coronary angiography for the first time for diagnostic purposes were enrolled in this study. The extent of the coronary lesion was assessed using the Friesinger Index, and subjects were classified into four groups: no lesions, minor lesions, intermediate lesions and major lesions. Serum biochemical parameters and serum concentrations of vascular cell adhesion molecule-1, intercellular adhesion molecule-1, E-selectin and matrix metalloproteinase 9 were analyzed.RESULTS:The vascular cell adhesion molecule-1 concentration was higher than 876 ng/mL in individuals with intermediate and major lesions (p<0.001 and p=0.020, respectively). Moreover, logistic regression analysis showed that these patients had an increased risk of having an intermediate lesion (p=0.007). Interestingly, all individuals with major lesions had vascular cell adhesion molecule-1 concentrations higher than 876 ng/mL. No association was found between the concentrations of the other proteins and the Friesinger Index.CONCLUSIONS:Serum vascular cell adhesion molecule-1 may be associated with the extent of coronary lesions. Moreover, it may represent an alternative to improve the cardiovascular risk classification in patients without acute coronary syndrome.