Serum Vascular Adhesion Protein-1 Research Articles

Serum vascular adhesion protein-1 is associated with twelve-year risk of incident cancer, cancer mortality, and all-cause mortality: a community-based cohort study.

Vascular adhesion protein-1 (VAP-1), a dual-function glycoprotein, has been reported to play a crucial role in inflammation and tumor progression. We conducted a community-based cohort study to investigate whether serum VAP-1 could be a potential biomarker for predicting incident cancers and mortality. From 2006 to 2018, we enrolled 889 cancer-free subjects at baseline. Serum VAP-1 levels were measured using a time-resolved immunofluorometric assay. Cancer and vital status of the participants were obtained by linking records with the computerized cancer registry and death certificates in Taiwan. During a median follow-up of 11.94 years, 69 subjects developed incident cancers and 66 subjects died, including 29 subjects who died from malignancy. Subjects in the highest tertile of serum VAP-1 had a significantly higher risk of cancer incidence (p=0.0006), cancer mortality (p=0.0001), and all-cause mortality (p=0.0002) than subjects in the other tertiles. The adjusted hazard ratios per one standard deviation increase in serum VAP-1 concentrations were 1.28 for cancer incidence (95% CI=1.01-1.62), 1.60 for cancer mortality (95% CI=1.14-2.23), and 1.38 for all-cause mortality (95% CI=1.09-1.75). The predictive performance of serum VAP-1 was better than that of gender, smoking, body mass index, hypertension, diabetes, and estimated glomerular filtration rate but lower than that of age for cancer incidence, cancer mortality, and all-cause mortality, as evidenced by higher increments in concordance statistics and area under the receiver operating characteristic curve. Serum VAP-1 levels are associated with a 12-year risk of incident cancer, cancer mortality, and all-cause mortality in a general population.

A Notorious Trio! Inflammation, Metabolic Syndrome and Vitiligo.

There is evidence to support that vitiligo is linked to metabolic syndrome (MS), confirming its systemic nature. However, the underlying pathogenic mechanisms remain unknown. To reveal the possible association of MS with vitiligo. We also attempted to study the connection between some inflammatory markers and MS in vitiligo patients to evaluate their utility in predicting MS risk. The study included 100 vitiligo patients with an age range between 18 to 60 years and 100 controls with matched age, gender, and body mass index. All subjects were tested for MS components. Serum visceral adipose tissue-derived serine protease inhibitor (vaspin), fatty acid binding protein 4 (FABP4), vascular adhesion protein 1 (VAP-1), chitinase-3-like protein 1 (YKL-40), and high-sensitivity C-reactive protein (hs-CRP) were also measured. Regarding MS, it was observed in 22.0% of vitiligo patients and 2.0% of control subjects (P < 0.001). Serum FABP4, VAP-1, YKL-40, and hs-CRP concentrations were higher in patients than in the control group (P < 0.05 each), and their levels showed high sensitivity and specificity to differentiate MS when using the receiver operating characteristic (ROC). Levels of these markers, except serum vaspin, were significantly positively correlated with lipid profile markers (except high-density lipoprotein cholesterol) and fasting blood glucose levels (P < 0.05 each). MS was more common in vitiligo patients. The levels of the biomarkers studied were significantly higher in vitiligo patients. Furthermore, their levels accurately predicted MS in vitiligo patients. According to current research, these markers may be useful in assessing MS risk in vitiligo patients. Extensive research, however, is required.

Vascular adhesion protein-1 and microvascular diabetic complications.

Vascular adhesion protein-1 (VAP-1) is a bifunctional protein that has the ability to catalyze the deamination of primary amines and is involved in the production of hydrogen peroxide, aldehydes, and advanced glycation end products (AGEs). VAP-1 is usually stored in intracellular vesicles of endothelial cells, smooth muscles, and adipocytes. It is responsible for leukocyte transmigration and adhesion. Overexpression of VAP-1 exacerbates oxidative stress and modulates a variety of inflammatory mediators linked with diabetic complications. Numerous studies have suggested the association of increased insulin levels with serum VAP-1 (sVAP-1). Preclinical research evidence suggests the increased activity of sVAP-1 in type 1 and 2 diabetes. Scientific reports on VAP-1 inhibitors have shown a reduction in severity in diabetic animal models. VAP-1 is a potential target of a therapeutically effective line of treatment for diabetes and diabetic complications such as nephropathy and retinopathy. The primary focus of this review is the role of VAP-1 in diabetes and its associated microvascular complications.

Assessment of relationship between serum vascular adhesion protein-1 (VAP-1) and gestational diabetes mellitus

Purpose: VAP-1 plays a crucial role in inflammation, oxidative stress and endothelial dysfunction which are main pathophysiologic mechanisms for gestational diabetes. We aimed to determine serum VAP-1 levels, assess its diagnostic value and correlation with clinical parameters in gestational diabetes.Methods: A total of 60 pregnant women with gestational diabetes and 75 healthy pregnant women between 24–28th gestational weeks between January–June 2017 were included. Pregnant women were screened for gestational diabetes by two-step protocol. Demographic, clinical and laboratory parameters of patients were recorded. VAP-1 was measured using an enzyme-linked immunosorbent assay method.Results: Gestational diabetes group had higher fasting and postprandial glucose, HbA1c, neutrophil-to-lymphocyte-ratio, platelet-to-lymphocyte-ratio, plateletcrit and C-reactive protein. Furthermore, VAP-1 levels were higher in gestational diabetes (3.35 ± 1.52 vs 2.2 ± 0.74; p < 0.001). VAP-1 levels >2.315 could predict gestational diabetes with a sensitivity of 70% and specificity of 65.3%. VAP-1 was correlated with clinical follow-up parameters such as fasting glucose (r = 0.473, p < 0.001), postprandial glucose (r = 0.416, p < 0.001), HbA1c (r = 0.462, p < 0.001) and inflammatory biomarkers such as platelet-to-lymphocyte-ratio (r = 0.254, p = 0.04), neutrophil-to-lymphocyte-ratio (r = 0.375, p = 0.003) and C-reactive protein (r = 0.306, p = 0.017).Conclusions: Elevated VAP-1 levels in gestational diabetes correlated with clinical follow-up and inflammatory markers may suggest the pathogenetic role of VAP-1 in gestational diabetes. Hence, we think that VAP-1 could be a promising marker for the prediction of gestational diabetes.

Serum vascular adhesion protein-1 is up-regulated in hyperglycemia and is associated with incident diabetes negatively.

Vascular adhesion protein-1 (VAP-1) can enhance tissue glucose uptake in cell studies and normalize hyperglycemia in animal studies. However, serum VAP-1 concentration (sVAP-1) is higher in subjects with diabetes in cross-sectional studies. In this cohort study, we test our hypothesis that sVAP-1 is increased in prediabetes to counteract hyperglycemia and is associated with incident diabetes negatively. From 2006 to 2012, 600 subjects without diabetes from Taiwan Lifestyle Study were included and followed regularly. Diabetes was diagnosed if FPG ≥ 126 mg/dL (7 mmol/L), 2-h plasma glucose (2hPG) during an oral glucose tolerance test (OGTT) ≥ 200 mg/dL (11.1 mmol/L), or hemoglobin A1c (HbA1c) ≥ 6.5%, or if the subject received anti-diabetic medications. Abdominal fat areas were measured by abdominal computed tomography and sVAP-1 was analyzed by ELISA. sVAP-1 was higher in subjects with prediabetes (p < 0.05) and increased during an OGTT (p < 0.001). Fasting sVAP-1 was associated with the response of sVAP-1 during an OGTT (p < 0.001). Besides, sVAP-1 was associated negatively with body mass index (BMI, r = -0.1449, p = 0.003), waist circumference (r = -0.1425, p = 0.004), abdominal visceral (r = -0.1457, p = 0.003), and subcutaneous (r = -0.1025, p = 0.035) fat areas, and serum high-sensitivity C-reactive protein (hsCRP) concentration (r = -0.2035, p < 0.0001), and positively with plasma adiponectin concentration (r = 0.2086, p < 0.0001), adjusted for age and gender. After 4.7 ± 2.6 years, 73 subjects (12.2%) developed incident diabetes. High sVAP-1 predicted a lower incidence of diabetes, adjusted for age, gender, BMI, family history of diabetes, HbA1c, HOMA2-%B and HOMA2-IR (HR = 0.66, 95% CI = 0.50-0.88, p < 0.01). sVAP-1 is increased in response to hyperglycemia. It is associated with obesity and serum hsCRP concentration negatively, and plasma adiponectin concentration positively. Besides, a high sVAP-1 is associated with a lower incidence of diabetes in human.

Correlation of serum vascular adhesion protein-1 with airflow limitation and quality of life in stable chronic obstructive pulmonary disease.

The serum vascular adhesion protein-1 (VAP-1) level increases in chronic inflammatory diseases. The present study aimed to examine serum VAP-1 level in patients with stable chronic obstructive pulmonary disease (COPD) and the correlation of this marker with airflow limitation and health-related quality of life using the COPD Assessment Test (CAT). We measured serum VAP-1 level in 43 patients with stable COPD and 30 control subjects and compared them with airflow limitation according to the COPD stage in the Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD) criteria, peripheral O2 saturation (SpO2), and CAT score. We also tested the association of serum VAP-1 level with COPD patients' clinical parameters. Serum VAP-1 level increased with increasing severity of COPD according to the GOLD classification (P=0.007). It also increased in patients with high CAT groups and high values on the modified Medical Research Council dyspnea scale (P=0.012 and P=0.015, respectively). In addition, there was a significant positive correlation between serum VAP-1 level and both SpO2 and CAT score (r=-0.404, P=0.007; r=0.482, P=0.001, respectively). The study showed that serum VAP-1 level increased with an increasing severity of obstruction in patients with stable COPD. This increase was associated with a reduced quality of life and increased severity of hypoxia. These results suggest that inhibiting serum VAP-1 level in COPD patients may be useful in managing the disease.

Investigating the safety and activity of the use of BTT1023 (Timolumab), in the treatment of patients with primary sclerosing cholangitis (BUTEO): A single-arm, two-stage, open-label, multi-centre, phase II clinical trial protocol

IntroductionPrimary sclerosing cholangitis (PSC) is a progressive inflammatory liver disease characterised by relentless liver fibrosis and a high unmet need for new therapies. Preventing fibrosis represents an important area of...

Vascular adhesion protein-1 in hemodialysis and hemodiafiltration patients: effect of single hemodialysis session on its level in regard to type of anticoagulant

PurposeTraditional anticoagulants used in intermittent hemodialysis (HD) are unfractionated heparin (UFH) and increasingly low molecular weight heparins (LMWHs). Repeated and prolonged exposure to UFH and/or LMWHs may further disturb hemostasis in uremic patients. Vascular adhesion protein-1 (VAP-1) is secreted by vascular smooth muscle cells, adipocytes and endothelial cells with functional monoamine oxidase activity and is elevated in atherosclerosis, diabetes mellitus and obesity. The aim of this study was to assess the effects of UFH and LMWHs on VAP-1 concentration in HD patients. The effects on single HD session on VAP-1 were also evaluated as well as VAP-1 levels in regard to type of renal replacement therapy.MethodsWe studied 82 hemodialyzed patients (mean age 63 years, dialysis vintage 59 months) and 17 patients treated by means of hemodiafiltration (HDF) (mean age 59 years, HD vintage 84 months, HDF 7 months). Patients were anticoagulated with enoxaparin (n = 46), dalteparin (n = 10), nadroparin (n = 6) or UFH (n = 20) during their HD sessions. VAP-1 was assessed using kits from BioVendor, Modrice, Czech Republic.ResultsPatients on HDF had significantly lower VAP-1 when compared with HD patients. We found that VAP-1 concentration in patients dialyzed by using LMWH or UFH was similar. There was no effect on HD session on VAP-1 concentration. Diabetic patients had higher serum VAP-1 than non-diabetic.ConclusionsHDF is associated with lower VAP-1 levels indicating less pronounced endothelial cell injury than hemodialysis. Type of heparin seems to have no effect on VAP-1 levels in hemodialyzed patients. However, the cross-sectional but not prospective design is a limitation of this study.

Serum vascular adhesion protein-1 is associated with obesity and predicts incident diabetes

Serum vascular adhesion protein-1 is associated with obesity and predicts incident diabetes

Serum Vascular Adhesion Protein-1 Predicts End-Stage Renal Disease in Patients with Type 2 Diabetes.

BackgroundDiabetes is the leading cause of end-stage renal disease (ESRD) worldwide. Vascular adhesion protein-1 (VAP-1) participates in inflammation and catalyzes the deamination of primary amines into aldehydes, hydrogen peroxide, and ammonia, both of which are involved in the pathogenesis of diabetic complications. We have shown that serum VAP-1 is higher in patients with diabetes and in patients with chronic kidney disease (CKD), and can predict cardiovascular mortality in subjects with diabetes. In this study, we investigated if serum VAP-1 can predict ESRD in diabetic subjects.MethodsIn this prospective cohort study, a total of 604 type 2 diabetic subjects were enrolled between 1996 to 2003 at National Taiwan University Hospital, Taiwan, and were followed for a median of 12.36 years. The development of ESRD was ascertained by linking our database with the nationally comprehensive Taiwan Society Nephrology registry. Serum VAP-1 concentrations at enrollment were measured by time-resolved immunofluorometric assay.ResultsSubjects with serum VAP-1 in the highest tertile had the highest incidence of ESRD (p<0.001). Every 1-SD increase in serum VAP-1 was associated with a hazard ratio of 1.55 (95%CI 1.12–2.14, p<0.01) for the risk of ESRD, adjusted for smoking, history of cardiovascular disease, body mass index, hypertension, HbA1c, duration of diabetes, total cholesterol, use of statins, ankle-brachial index, estimated GFR, and proteinuria. We developed a risk score comprising serum VAP-1, HbA1c, estimated GFR, and proteinuria, which could predict ESRD with good performance (area under the ROC curve = 0.9406, 95%CI 0.8871–0.9941, sensitivity = 77.3%, and specificity = 92.8%). We also developed an algorithm based on the stage of CKD and a risk score including serum VAP-1, which can stratify these subjects into 3 categories with an ESRD risk of 0.101%/year, 0.131%/year, and 2.427%/year, respectively.ConclusionsIn conclusion, serum VAP-1 can predict ESRD and is a useful biomarker to improve risk stratification in type 2 diabetic subjects.

Evaluation of Serum Vascular Adhesion Protein-1 as a Potential Biomarker in Thyroid Cancer.

Vascular adhesion protein-1 (VAP-1) is a glycoprotein that mediates tissue-selective lymphocyte adhesion. The prognostic value of VAP-1 has been determined in gastric cancer. The aim of this study was to evaluate the changes and the predictive value of serum VAP-1 in patients with thyroid cancer. A total of 126 patients with thyroid nodules and 53 healthy controls participated in this study. The patients were further divided into subgroup 1 (69 cases with benign thyroid nodules) and subgroup 2 (57 cases with thyroid cancer). Serum VAP-1 was measured by time-resolved immunofluorometric assay. Diagnostic value of presurgical VAP-1 for thyroid cancer was conducted by receiver operating characteristic (ROC) curves. Serum levels of VAP-1 were significantly lower in thyroid cancer group than in healthy control and benign thyroid nodule groups. VAP-1 concentrations negatively correlated with serum thyroglobulin (Tg) levels in thyroid cancer patients (r = −0.81; p < 0.001). The optimum cut-off value of VAP-1 was 456.6 ng/mL with a 77.4% specificity and 66.7% sensitivity for thyroid cancer diagnosis. Serum VAP-1 decreased in thyroid cancer patients and VAP-1 could be a potential useful adjunct biomarker in the diagnosis of thyroid cancer.

Serum vascular adhesion protein-1 level predicts risk of incident cancers in subjects with type II diabetes.

Serum vascular adhesion protein-1 (VAP-1) predicts cancer-related mortality in diabetic subjects. However, whether serum VAP-1 predicts cancer incidence or cancer progression remains unclear. We conducted a cohort study to investigate whether serum VAP-1 and related clinical variables predict incident cancers in type II diabetic subjects. From 1996 to 2003, we enrolled 568 type II diabetic subjects who were free of cancer at baseline. Serum VAP-1 at enrollment was measured by time-resolved immunofluorometric assay. Chronic kidney disease (CKD) was defined as estimated glomerular filtration rate <60 mL/min per 1.73 m(2). The subjects were followed until first occurrence of cancer or until December 31, 2011. During a mean follow-up of 11.3 years, 71 subjects developed incident cancers. The HRs for incident cancers in subjects with highest tertile of serum VAP-1 and in subjects with CKD were 2.95 [95% confidence interval (CI), 1.31-6.63; P = 0.009] and 2.29 (95% CI, 1.18-4.44; P = 0.015), respectively, after multivariate adjustment. There was an interaction between serum VAP-1 and CKD on the risk of incident cancers (P = 0.01 for log-transformed VAP-1 × CKD). The relationship among serum VAP-1, CKD, and incident cancers was similar if death was considered in the competing risk models or if subjects with shorter follow-up period were excluded. Higher serum VAP-1 and CKD can independently predict future development of cancers in type II diabetic subjects. Physicians should be aware of the early signs of cancer in diabetic individuals with elevated VAP-1 or renal dysfunction. More aggressive treatment strategies might be considered.

Vascular Adhesion Protein-1 Is Significantly Elevated in Heart Transplant Recipients and Chronic Heart Failure Patients With Comorbidities.

Background: VAP-1 (vascular adhesion protein-1) is a copper-containing SSAO (semi-carbazide sensitive amine oxidase) secreted by vascular smooth muscle cells, adipocytes, and endothelial cells with functional monoamine oxidase activity. The oxidation process generates harmful products that may be involved in causing atherosclerosis and vascular damage in diabetes. Elevation of SSAO activity is observed in atherosclerosis, diabetes mellitus and obesity. Taking all these data into consideration, the aim of the study was to assess VAP-1 levels and its correlations with endothelial injury markers in prevalent heart allograft recipients (n=128) and patients with chronic heart failure (n=78). Methods:Complete blood count, urea, serum lipids, fasting glucose, creatinine, were studied by standard laboratory method in the hospital central laboratory. We assessed markers of endothelial function/injury and inflammation: vWF (von Willebrand factor), TWEAK, C-Reactive Protein with commercially available assays. Results: The mean serum VAP-1 in was lower than in patients with chronic heart failure. In patients with chronic heart failure VAP-1 was related to age (0.31,p<0.01), ejection fraction-EF (r=0.23, p<0.05), presence of hypertension (r=0.28, p<0.01), presence of diabetes (r=0.31,p<0.01), TWEAK (r=0.21, p<0.05). In heart transplant recipients VAP-1 correlated with estimated glomerular filtration rate-eGFR (r=-0.19, p<0.05), age (r=0.17, p<0.05), presence of diabetes (r=0.29, p<0.01), EF (r=-0.34, p<0.01), presence of hypertension (r=0.22, p<0.05), TWEAK (r=0.17, p<0.05), NYHA class (0.33, p<0.001). In both groups of the studied patients VAP-1 was significantly higher in patients with diabetes, hypertension, and eGFR< 60 ml/min when compared to patients without diabetes, with normotension and eGFR> 60 ml/min.(all p<0.01). Concluding, VAP-1, elevated predominantly in patients with comorbidities such as diabetes, hypertension chronic kidney disease may contribute to the worse outcomes in both of the population studied. It may also contribute to the progression of atherosclerosis with its complications.

Relationship between Serum Soluble Vascular Adhesion Protein-1 Level and Gastric Cancer Prognosis

Background: Vascular adhesion protein-1 (VAP-1) is a glycoprotein that mediates tissue-selective lymphocyte adhesion in a sialic acid-dependent manner. The prognostic importance of VAP-1 was determined in various human cancers. The aim of this study was to determine the relationship between VAP-1 and prognosis of gastric cancer. Materials and Methods: Serum of operable and metastatic gastric cancer patients was collected before treatment (surgery, radiotherapy, and/or chemotherapy). VAP-1 levels were measured by enzyme-linked immunosorbent assay. Results: A total of 86 gastric cancer patients (32 female, 54 male) were included in the study. Curative surgical treatment was performed in 54 (62.8%) patients. The mean serum VAP-1 level was 324.4 pg/ml and significantly higher in operable gastric cancer patients compared to metastatic gastric cancer patients (383.1 ± 173.5 vs. 225.2 ± 113.9 pg/ml; p < 0.001). When a cut-off value for VAP-1 of 218.8 pg/ml was determined by receiver operating characteristic (ROC) curves for presence of metastasis, sensitivity and specificity were 81.5 and 65.6%, respectively. Patients with decreased VAP-1 levels had a significantly poorer prognosis compared to patients with increased serum VAP-1 levels (median survival 8.2 vs. 23.5 months; p < 0.001). Multivariate analysis showed that VAP-1 is an independent prognostic factor of gastric cancer (odds ratio 2.3, 95% confidence interval 1.1-4.9; p = 0.032). Conclusion: A low serum VAP-1 level may be an indicator of poor prognosis in gastric cancer. This study demonstrated that low serum VAP-1 levels are associated with poor prognosis in gastric cancer patients.

VAP-1 in peritoneally dialyzed patients

VAP-1 (vascular adhesion protein-1) possesses semicarbazide-sensitive amine oxidase (SSAO) activity. It has also been found that serum VAP-1 was elevated in acute and chronic hyperglycemia and in patients with diabetes as well as in chronic kidney disease. Renalase, with possible monoamine oxidase activity, which breaks down catecholamines such as SSAO, is expressed in the endothelium as well as in the kidney. The aim of the study was to assess serum VAP-1 levels in peritoneally dialyzed (PD) patients and factors explaining its variability. This pilot study was performed on 25 peritoneally dialyzed patients, including 4 patients with type 2 diabetes. We found that the mean VAP-1 was significantly higher in chronic ambulatory peritoneal dialysis (CAPD) patients when compared to the control group (p<0.05). Dopamine was significantly lower in PD patients when compared to the healthy volunteers (p<0.05), whereas noradrenaline was significantly higher in PD patients relative to the healthy volunteers (p<0.01). There was a significant difference in the VAP-1 concentration in the group with and without residual renal function (p<0.05) as well as between 10 patients with hyperglycemia when compared to patients with normoglycemia (p<0.05). There was no effect of gender on the serum VAP-1 levels. In PD patients VAP-1 correlated with systolic blood pressure (r=-0.4, p<005), residual renal function (r=-0.62, p<0.05), and glucose (=0.54, p<0.05). We concluded that VAP-1, elevated in patients on PD, was predominantly dependent on residual kidney function and glucose level, factors both linked to endothelial damage and cardiovascular complications.

Serum vascular adhesion protein-1 predicts all-cause mortality and cancer-related mortality in subjects with colorectal cancer

BackgroundVascular adhesion protein-1 (VAP-1) participates in inflammation and catalyzes the breakdown of amines to produce aldehyde, hydrogen peroxide, and ammonia. Serum VAP-1 can predict cancer mortality, including colorectal cancer (CRC) mortality, in type 2 diabetic subjects. However, it remains unknown if serum VAP-1 can predict mortality in CRC patients. This prospective cohort study investigates if serum VAP-1 is a novel biomarker for mortality prediction in CRC. MethodsWe enrolled 300 CRC patients. Preoperative serum VAP-1 was measured by time-resolved immunofluorometric assay. They were followed until September 2009 or death, which was ascertained by the National Death Registration System. ResultsThe median follow-up period was 4.7years. Compared with normal counterpart, VAP-1 immunoactivity was upregulated in CRC tissues, especially at the invasion front. Serum VAP-1 can independently predict all-cause mortality (HR: 1.0026, 95% CI: 1.0003–1.0050, P<0.05) and cancer-related mortality (HR: 1.0026, 95% CI: 1.0001–1.0050, P<0.05). A risk score composed of age, gender, carcinoembryonic antigen (CEA) >5ng/ml, tumor grading, tumor staging, and serum VAP-1 could stratify CRC patients into low-, intermediate-, and high-risk subgroups, with a 5-year mortality rate of 10%, 34%, and 78%, respectively. ConclusionsSerum VAP-1 predicts mortality independently and improves risk stratification in CRC subjects.

Methylentetrahydrofolatereductase (rs1801133) polymorphism and psoriasis: contribution to oxidative stress, lipid peroxidation and correlation with vascular adhesion protein 1, preliminary report

Psoriatic patients are at greater risk of oxidative stress and inflammation which is associated with abnormal plasma lipid metabolism and lipid peroxidation.There is not any information about the clinical significance of relation between methylentetrahydrofolatereductase (MTHFR) 677-T allele with malondialdehyde (MDA), lipids, apolipoproteins and vascular adhesion protein-1 (VAP-1) partakes in the migration process of lymphocytes into sites of inflammation. This study is the first investigation to examine the association of MTHFR (rs1801133) C677T polymorphism, serum level of MDA, VAP-1, lipid-lipoprotein and apolipoproteins with the risk of psoriasis. The present case-control study consisted of 100 psoriatic patients and 100 gender- and age-matched unrelated healthy controls from west population of Iran. MTHFR-C677T (rs1801133) polymorphisms were detected by restriction fragment length polymorphism (PCR-RFLP), VAP-1 by ELISA, apolipoproteins by immunoprecipitation, lipid and apolipoproteins by spectrophotometery and MDA by HPLC. We found that dominant/recessive model (CC+CT/TT) and T allele of MTHFR-677 alleles significantly 7.45 and 1.76 times increased risk of psoriasis, respectively. The psoriasis patients with MTHFR-677-T (C/T+T/T) allele had significantly higher serum MDA, VAP-1 and apolipoproteinsAPOB concentrations and ratio of APOB/APOA1 than the control subjects.The MTHFR-677-T allele frequencies in psoriasis patients were significantly higher than that in control group (28.5% vs. 18.5%; P=0.018).We found a significant positive correlation between VAP-1 with MDA (P=0.047) and LP (a) (P=0.025). In the present study, we demonstrated for the first time that the psoriasis patients with MTHFR-677-T (C/T+T/T) allele had higher serum levels of MDA, VAP-1, APOB and ratio of APOB/APOA1 and dominant/recessive model (CC+CT/TT) and T allele of MTHFR-677 are significantly more common in psoriasis and increased risk of psoriasis by 7.45 and 1.76 fold, respectively. These data suggest that psoriasis patients carrying of TT genotypes and T allele of MTHFR-677 may be more susceptible to cardiovascular disease and myocardial infarction.

Serum vascular adhesion protein-1 level is higher in smokers than non-smokers

Background: Semicarbazide-sensitive amine oxidase (SSAO)/vascular adhesion protein-1 (VAP-1) is involved in the pathogenesis of both atherosclerosis and cancer. Because chemical components and metabolites of cigarettes are deaminated by SSAO, the relationship between smoking and serum SSAO/VAP-1 was studied in humans.Methods: A total of 451 non-diabetic and normoalbuminuric Han Chinese subjects were recruited to participate in this study. Smoking history was obtained by using a questionnaire and those who smoked more than 100 cigarettes during a 6-month period were considered smokers. Serum VAP-1 concentration was measured by time-resolved immunofluorometric assay. Age, gender, waist circumference and estimated glomerular filtration rate (GFR) were adjusted in different statistical models.Results: Smokers were mainly male (85.7% versus 26.3%) and were more obese than non-smokers (p < 0.05). Subjects with higher serum VAP-1 concentrations were older (p < 0.001) and tended to have larger waist circumferences and lower estimated GFR. Serum VAP-1 concentration was higher in smokers than in non-smokers (p < 0.05) after adjusting for age, gender, waist circumference, estimated GFR, liver biochemistry and lipid profile.Conclusions: Cigarette smoking is associated with elevated serum VAP-1 concentration. Whether VAP-1 and its SSAO activity link the relationship between cigarette smoking, atherosclerosis and cancer requires further investigation.

VAP-1, a Novel Molecule Linked to Endothelial Damage and Kidney Function in Kidney Allograft Recipients

VAP-1 (vascular adhesion protein-1) is a copper-containing SSAO (semi-carbazide sensitive amine oxidase) secreted by vascular smooth muscle cells, adipocytes, and endothelial cells with functional monoamine oxidase activity. The oxidation process generates harmful products that may be involved in causing atherosclerosis and vascular damage in diabetes. Elevation of SSAO activity is observed in atherosclerosis, diabetes mellitus and obesity. On the other hand, renalase, with possible monoamine oxidase activity, which breaks down catecholamines like SSAO, is also expressed in the endothelium as well as in the kidney The aim of the study was to assess VAP-1 levels and its correlations with endothelial injury markers and renalase in 50 kidney allograft recipients. Methods: Complete blood count, urea, serum lipids, fasting glucose, creatinine, were studied by standard laboratory method in the hospital central laboratory. We assessed markers of endothelial function/injury: vWF (von Willebrand factor), thrombomodulin, ICAM (intracellular adhesion molecule), VCAM (vascular cell adhesion molecule), CD40L, CD44, CD146, inflammation: hsCRP, and IL-6 and adipocytokines: leptin, adiponectin, visfatin, apelin with commercially available assays. Results: The mean serum VAP-1 in Tx was significantly higher comparing to the control group. In kidney transplant recipients VAP-1 correlated with BMI (r=0.39, p< 0.01), CD44 (r=0.27, p< 0.05), hsCRP (r=0.28, p< 0.05), serum creatinine (r=0.29, p< 0.05), eGFR (CKD-EPI formula r=-0.27, p< 0.05, by MDRD r=-0.27, p< 0.05, by Cockcroft-Gault r=-0.35, p< 0.01), serum urea (r=0.27, p< 0.05), CD146 (r=0.49, p< 0.001), CD40L (r=0.26, p< 0.06), and renalase (r=0.34, p< 0.05)Figure: [VAP-1 and renalase in Ktx]In multiple regression analysis VAP-1 was predicted 80% by serum creatinine (beta value 0.33, p=0.01), and CD146 (beta value 43, p=0.0005) F=12.26, SE= 71.83 and p< 0.000001. Concluding, VAP-1, elevated in kidney transplant recipients, is predominantly dependent on endothelial damage and kidney function, which deteriorated with time after kidney transplantation and age.

Serum Vascular Adhesion Protein-1 correlates with vascular endothelial growth factor in patients with type II diabetes

AimsTo study serum levels of soluble vascular adhesion protein (sVAP)-1 in type II diabetic patients with retinopathy. MethodsSerum samples were obtained from 53 consecutive patients, including 14 cases with non-angiogenic ocular diseases, i.e., epiretinal membrane (ERM) and idiopathic macular hole (MH), 19 cases with age-related macular degeneration (AMD), and 20 cases with diabetic retinopathy (DR). Protein levels of sVAP-1, intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, and vascular endothelial growth factor (VEGF) were determined by enzyme-linked immunosorbent assay. Enzymatic activity of semicarbazide-sensitive amine oxidase (SSAO) was also measured. ResultsSerum level of sVAP-1 showed a moderate correlation with SSAO activity in all cases. Patients with DR had higher levels of serum sVAP-1 than subjects with ERM and MH, or those with AMD; however, severity of DR is not related to the serum levels of sVAP-1. Serum sVAP-1 correlated positively with VEGF in patients with DR, but not in those with ERM and MH, or those with AMD. Neither soluble ICAM-1 nor VCAM-1 correlated with VEGF, even in subjects with DR. ConclusionThe current data demonstrate the elevated serum levels of sVAP-1 and correlation between sVAP-1 and VEGF in patients with type II diabetes.