Serum Angiogenin Concentrations Research Articles

SUN-271 THE CHANGES OF NEUTROPHIL ACTIVATION MARKERS, ANGIOGENIN, FGF-23 AS CKD ADVANCED AND THOSE EFFECTS ON ARTERIAL STIFFNESS

Arterial stiffness (AS) has been identified as independent predictors of cardiovascular mortality in patients with chronic kidney disease (CKD). The number of circulating neutrophils, neutrophil activation markers and oxidative status were increased in CKD. There was a past report that serum angiogenin concentration was increased in patients with stage IV PAOD and may be used as markers of PAOD severity. In addition, there was a recent paper that the increase of serum FGF-23 as ADPKD stage advanced was associated with the development of AS.

The Potential of Angiogenin as a Serum Biomarker for Diseases: Systematic Review and Meta-Analysis.

Background Angiogenin (ANG) is a multifunctional angiogenic protein that participates in both normal development and diseases. Abnormal serum ANG levels are commonly reported in various diseases. However, whether ANG can serve as a diagnostic or prognostic marker for different diseases remains a matter of debate. Methods Here, we performed a systematic review and meta-analysis of the literature utilizing PubMed, Web of Science, and Scopus search engines to identify all publications comparing plasma or serum ANG levels between patients with different diseases and healthy controls, as were studies evaluating circulating ANG levels in healthy populations, pregnant women, or other demographic populations. Results This study demonstrated that the serum ANG concentration in healthy populations was 336.14 ± 142.83 ng/ml and remained relatively stable in different populations and regions. We noted no significant differences in serum ANG levels between patients and healthy controls, except in cases in which patients suffered from cancer or cardiovascular diseases. The serum ANG concentrations were significantly higher in patients who developed colorectal cancer, acute myeloid leukemia, multiple myeloma, myelodysplastic syndromes, and heart failure than those in healthy controls. Conclusion ANG has the potential of being a serum biomarker for cancers and cardiovascular diseases.

Angiogenin expression in the sera and skin of patients with rheumatic diseases

Vascular abnormalities are one of the common features in rheumatic diseases, but their pathogenesis is still not known. Angiogenin, a molecule implicated in the angiogenic process, may play some roles in such vascular changes. Serum angiogenin concentrations were measured in 21 scleroderma patients, 10 patients with systemic lupus erythematosus (SLE), 21 patients with dermatomyositis (DM), 5 patients with polymyositis (PM), 11 patients with clinically amyopathic DM (CADM) and 12 normal subjects, with specific enzyme-linked immunosorbent assays. Angiogenin mRNA in vivo was determined in skin tissues of 5 DM patients, 4 CADM patients, 5 SLE patients and 7 normal subjects using quantitative real-time polymerase chain reactions. We could not find any significant differences in the serum angiogenin levels among normal subjects and patients with rheumatic diseases. However, when we evaluated the correlation of serum angiogenin levels with clinical features of 32 DM/CADM patients, the patients with increased angiogenin levels had significantly higher aldolase levels than those with decreased levels. On the other hand, angiogenin mRNA is significantly up-regulated in the involved skin of DM and CADM, suggesting that angiogenin expression is up-regulated locally in the skin but not in sera of patients with DM and CADM. In conclusion, dysregulated angiogenin expression may contribute to the pathogenesis of myositis as well as skin involvement via the vascular change in DM/CADM. Further studies with an increased number of patients may help to clarify the relationship between angiogenin and vascular abnormalities in rheumatic diseases and to develop new therapeutic strategies.

Angiogenin in middle-aged type 1 diabetes patients

BackgroundAngiogenin levels are increased in children and adolescent patients with type 1 diabetes, regardless of the extent of diabetic microangiopathy. However, little is known about the angiogenin concentrations in adults with type 1 diabetes. Thus we studied its level in middle aged subjects with the presence of diabetic nephro-, retino and neuropathy. MethodsWe investigated the data of 57 (age 39±6.6years, 45.6% of males) patients with type 1 diabetes and 38 age-matched control subjects without diabetes (age 37.1±5.9years, 42.1% of males), including medical histories, evidences of microangiopathy and serum angiogenin concentrations. ResultsSerum angiogenin level was lower in patients with type 1 diabetes [384.2(190.4–999.8)ng/ml] compared to controls [460.4(230.6–708.2)ng/ml], p=0.04.In patients with overt diabetic nephropathy the angiogenin level was higher when compared to patients without nephropathy [568.2(269.6–999.8) vs 369.4(190.4–999.8)ng/ml, p=0.01]. There were no differences between angiogenin levels in subgroups of patients distinguished by the presence of other microvascular complications or other concomitant vascular risk factors despite cigarette smoking [smokers: 516.2(294.4–999.8) vs. non-smokers: 372.1(190.4–924.8)ng/ml, p=0.01]. ConclusionsRegardless of the presence of diabetic microangiopathy, angiogenin level in middle-aged type 1 diabetes patients is lower than in controls. The presence of overt nephropathy and smoking habit in middle-aged patients with type 1 diabetes are associated with higher angiogenin level.

High serum angiogenin at diagnosis predicts for failure on long-term treatment response and for poor overall survival in non-Hodgkin lymphoma

Background Angiogenin is a potent inducer of angiogenesis. We prospectively evaluated the prognostic significance of serum angiogenin from 204 consecutive non-Hodgkin lymphoma (NHL) patients diagnosed and treated in a single institution. Methods Serum angiogenin, VEGF, and bFGF concentrations at diagnosis were determined using a quantitative sandwich enzyme immunoassay technique. Kaplan–Meier survival curves were compared by the log-rank test. Multivariate survival analyses were performed using the parametric model of Weibull and the non-parametric proportional hazards model of Cox. Results Patients with a high serum angiogenin at diagnosis (>median; 401 ng/ml) had significantly lower 5-year survival rate than those with a low (⩽median) angiogenin (42% versus 63%, respectively; P = 0.0073). Serum angiogenin provided additional information to the International Prognostic Index (IPI) identifying a subgroup (serum angiogenin >median and IPI > 1) with very poor prognosis (5-year survival 19%, P < 0.0001). In receiver operating characteristic (ROC) analyses the accuracy of the IPI to correctly classify patients with favourable or poor survival was improved from fair to good by complementing the IPI with serum angiogenin concentration. With patients who initially achieved complete response (CR) after chemotherapy, a high angiogenin at diagnosis (>median; relative risk (RR) 2.38; P = 0.0077) and an advanced tumour stage (III–IV; RR 2.41; P = 0.0087) were the only independent predictors for patients with unfavourable outcome although first responding well to therapy. Conclusions We conclude that elevated serum angiogenin surfaced as an independent predictor for failure in long-term treatment response and for poor overall survival in a series of 204 NHL patients, and might thus also complement the IPI in identifying the patients with particularly aggressive and/or treatment resistant disease.

Angiogenin and SDF-1α serum concentration in patients with systemic sclerosis in relation to clinical status

IntroductionSystemic sclerosis (SSc) is a connective tissue disorder characterized by tissue hypoxia due to vascular changes and excessive fibrosis of the skin and internal organs. Damage to blood vessels and endothelium, as well as imbalance of vascular homeostasis, impairment of angiogenesis and vasculogenesis are observed in the course of the disease. The aim of the study was to investigate the pro-angiogenic factors angiogenin and SDF-1α in patients with SSc.Material and methodsSerum samples were collected from 50 patients with dSSc (diffuse SSc) and lSSc (limited SSc) and from 38 patients used as a healthy control group. We explored: 1) how the serum concentrations of SDF-1α and angiogenin differ in the investigated groups; 2) the correlation among chemokines in SSc and the duration of the disease, Raynaud’s phenomenon, sclerosis of the skin and TSS (total skin score).ResultsPatients with SSc showed statistically significantly higher serum angiogenin concentration and there was no correlation between duration of the disease and Raynaud’s phenomenon, skin sclerosis or TSS. There was also no difference or no correlation between serum level of SDF-1α and the investigated groups.ConclusionsThe increase in angiogenin concentration in the serum in patients with SSc may confirm endothelial damage caused by hypoxia and reduced vascular perfusion due to the course of SSc without contributing to compensatory revascularization.

Angiogenin in sera as an independent prognostic factor in gastric cancer.

The purpose of this study is to elucidate an increased expression of angiogenin (ANG) as a prognostic factor of gastric cancer (GC), against the background of our previous observations of the increased expression of ANG in the more progressed GC. We investigated serum ANG concentrations in 123 GC patients and 63 healthy volunteers as well as the distributions of ANG gene message in 52 GC tissues by in situ hybridization. The prognostic significance of ANG was investigated by the Cox proportional hazards model including variable selection and by survival analysis. The mean serum ANG concentrations in GC patients (378.3+/-95.5 ng/ml) were significantly higher (P=0.0001) than those in the healthy volunteers (334.1+/-58.2 ng/ml). Either strong, moderate, weak, or no ANG gene message expression was seen in 25, 22, 4, and 1 patients, respectively, in GC cells as well as in interstitial cells in the vicinity of cancer cells, a finding in accord with our previous results of ANG protein localization. The variable selection method selected increased (> or =400 ng/ml) serum ANG concentration (P=0.02), undifferentiated histological type (P=0.01), cancer depth (P=0.001), and third-tier lymph node involvement (P=0.0005) as an independent prognostic factor by the Cox proportional hazards model. A significant correlation was seen between higher serum ANG concentrations (> or =400 ng/ml) and worse disease-free (P=0.003) or disease-specific (P=0.03) survivals. CONCLUSIONS. These results suggest that serum levels of ANG are an independent prognostic factor that could be a predictor of postoperative outcomes of GC patients.

Increased angiogenin expression in gastric cancer correlated with cancer progression.

The purpose of this study is to elucidate the expression of angiogenin and its previously undemonstrated clinical significance in gastric cancer (GC). Angiogenin expression was examined immunohistochemically in 21 GC tissues and 21 corresponding normal gastric tissues. The serum concentration was determined by enzyme-linked immunosorbent assay (ELISA) in GC patients preoperatively (n = 48) and postoperatively (n = 41), in nonneoplastic patients preoperatively (n = 23) and postoperatively (n = 19), and in 32 healthy volunteers. The amount of angiogenin in the tissue of 21 GC patients was also determined by ELISA. Angiogenin expression was observed in GC cells as well as in some fundic glandular cells and some inflammatory cells. The mean serum concentration in GC patients (407.8 +/- 105.2 ng/ml) was significantly higher than that in the nonneoplastic patients (345.7 +/- 58.3 ng/ml; P < 0.003) and in the healthy volunteers (333.0 +/- 59.3 ng/ml; P < 0.0002). The mean serum angiogenin concentrations were progressively higher in the order T1 + T2 (P < 0.04) < T3 + T4 (P < 0.0001) < recurrent GC (P < 0.05) subgroups, in the order node-negative (P < 0.05) < node-positive (P < 0.0002) subgroups, and in the order stage I +II (P < 0.02) < stage III and over (P < 0.0005) subgroups as compared with those in the healthy volunteers. These elevated serum angiogenin concentrations in each subgroup were significantly (P < 0.0003) reduced after cancer resection. The amounts of angiogenin in GC tissues correlated significantly with the serum angiogenin concentration (P < 0.01). These results suggest that angiogenin expression is increased in GC and that the increased serum concentration in GC patients correlates with cancer progression.

Serum Angiogenin Levels during Menstrual Cycle and Pregnancy

Objective: To evaluate alterations in maternal circulating angiogenin levels with advancing gestation and to assess the effect of labor stress on serum angiogenin levels in neonates delivered vaginally and by cesarean section. Methods: The maternal circulating angiogenin concentrations were compared in 37 normotensive nonpregnant women, in 60 normotensive pregnant women from 7 to 41 weeks of gestation, and in 12 normotensive postpartum women on the 3rd puerperal day. The serum angiogenin concentrations were also measured in 12 patients with threatened premature labor. Moreover, maternal and fetal serum angiogenin samples before and after delivery were used to determine differences in 12 neonates delivered vaginally and in 11 neonates delivered by elective cesarean section. The serum angiogenin level was measured using an enzyme-linked immunosorbent assay. Results: There was no significant difference in serum angiogenin levels during each phase of the menstrual cycle. The serum angiogenin levels were decreaseing until 15 weeks of gestation and increasing thereafter. There was no significant difference in serum angiogenin levels between normal pregnant women and in patients with threatened premature labor. Labor stress did not affect either maternal or fetal serum angiogenin concentrations. The serum angiogenin levels of the neonates were significantly lower than those in maternal serum after both vaginal delivery and delivery by cesarean section. Conclusion: These results suggest that regulatory mechanisms of angiogenin may exist during pregnancy.

Increased angiogenin expression in the tumor tissue and serum of urothelial carcinoma patients is related to disease progression and recurrence

The progression of solid tumors is at least partly dependent on angiogenesis, the induction of which is mediated by several angiogenic factors, including angiogenin (ANG). The authors evaluated the expression of ANG in the tumor tissue and serum of patients with urothelial carcinoma. The expression of ANG in 5 human bladder carcinoma cell lines and 24 urothelial carcinomas (10 superficial carcinomas and 14 invasive carcinomas) and in corresponding normal urothelial tissues was investigated by reverse transcriptase-polymerase chain reaction and Northern blot analysis. Serum levels of ANG in 52 healthy volunteers and in 135 patients with urothelial carcinomas (81 superficial carcinomas and 54 invasive carcinomas) were measured by using a sandwich enzyme immunoassay. ANG mRNA transcripts were detected in all of the bladder carcinoma cell lines, urothelial carcinomas, and normal tissues. The mean level of ANG expression in invasive urothelial carcinomas was 4-fold higher than in superficial carcinomas and 5-fold higher than in normal tissues. The mean serum ANG concentration for invasive urothelial carcinoma patients (514.6+/-211.1 ng/mL) was significantly higher than for superficial urothelial carcinoma patients (381.7+/-169.3 ng/mL) and healthy volunteers (337.5+/-71.4 ng/mL). The overall survival rate of patients with elevated serum levels of ANG was significantly lower than that of patients with normal levels. Moreover, among the 47 patients with advanced urothelial carcinoma who underwent complete resection, the disease free survival rate of patients with elevated serum levels of ANG was significantly lower than that of patients with normal levels. These results indicate that ANG is strongly expressed in the tumor tissue and is present in high levels in the serum of patients with invasive urothelial carcinoma compared with superficial carcinoma patients and that elevation of serum ANG level could be used as a novel predictor of the prognoses of patients with urothelial carcinoma.

Increased angiogenin expression in obstructive chronic pancreatitis surrounding pancreatic cancer but not in pure chronic pancreatitis.

We previously demonstrated the increased expression of angiogenin (ANG) in pancreatic cancer and its relation to cancer aggressiveness; however, the expression patterns and the roles of angiogenin in chronic pancreatitis are still unknown. We investigated the expression of ANG both in the tissues and in the sera of chronic pancreatitis patients (pure chronic pancreatitis) by using in situ hybridization, Western blot analysis, and enzyme-linked immunosorbent assay. In situ hybridization revealed no detectable ANG messenger RNA (mRNA) signals in all tissues of pure chronic pancreatitis and normal pancreas. Only a small amount of protein band expression was obtained in all of the protein lysates of pure chronic pancreatitis and normal pancreas. Accordingly, there was no significant difference between the mean serum ANG concentration of chronic pancreatitis patients (352.1+/-72.5 ng/ml) and that of healthy volunteers (357.6+/-45.2 ng/ml). By contrast, acinar cells and interstitial fibroblasts in the tissues surrounding pancreatic cancer showed increased ANG mRNA expression. Strong protein band expression was obtained in the protein lysates of pancreatic cancer surrounding tissue, and mean serum ANG concentration was increased in pancreatic cancer patients. These findings suggest that ANG expression is increased in pancreatic cancer surrounding tissue but is not increased in pure chronic pancreatitis, and that ANG is potentially involved in the pancreatic cancer microenvironment rather than the establishment of pure chronic pancreatitis.