sVEGFR-1 Concentrations Research Articles

Antenatal maternal serum biomarkers as a predictor for placenta accreta spectrum disorders

IntroductionPlacenta accreta spectrum (PAS) disorder, an abnormal adherence of the placenta to the uterine wall, with variable degrees of invasion, is a major cause of maternal morbidity and mortality associated with severe postpartum hemorrhage. PAS is diagnosed using ultrasonography or with magnetic resonance imaging; in many centers there is a lack of PAS diagnostic expertise in diagnosing. Hence, we investigated the performance of selected maternal plasma protein biomarkers, antithrombin-III (AT-3), plasminogen activator inhibitor-I (PAI-I), soluble vascular endothelial growth factor receptor-II (sVEGFR-2), and soluble Tie-II (sT-2) for prenatal screening in pregnancies at a high risk of PAS. MethodsThis prospective study, conducted in a tertiary hospital from September 2021 to May 2022, included pregnant women with placenta previa suspicious of PAS between 28 and 42 weeks of gestation. Four serum samples were collected from each woman to evaluate serum concentrations and compared between placenta previa (control) and PAS groups. The screening performances of the biomarkers were analyzed, and the best screening model for PAS was created. ResultsTwenty-two women with PAS and 18 with placenta previa alone were included (n = 40). The median concentrations of PAI-I, AT-3, sVEGFR-2, and sT-2 among the PAS group were 21.2, 6154.6, 7.5, and 12.8 ng/mL, respectively. The best screening model for PAS combined all four biomarkers with a history of cesarean delivery (77 % sensitivity, 89 % specificity, and an AUC of 0.87). DiscussionA combination of the four maternal serum biomarkers in women with a history of cesarean delivery presented the most promising model for prenatal screening of PAS. ConclusionA combination of the four maternal serum biomarkers with a history of cesarean delivery presented the most promising model for prenatal screening of PAS.

Unraveling the Angiogenic Puzzle: Pre-Treatment sVEGFR1 and sVEGFR2 Levels as Promising Prognostic Indicators in Early-Stage Breast Cancer Patients.

Despite the advancements in breast cancer (BrC) diagnosis and treatment, a considerable proportion of patients with early-stage disease still experience local recurrence or metastasis. This study aimed to assess the levels of specific angiogenic parameters in the EDTA plasma of BrC patients before and after treatment and to explore their clinical and prognostic significance. The levels of vascular endothelial growth factor A (VEGF-A), soluble form of vascular endothelial growth factor receptor type 1 (sVEGFR1), and soluble form of vascular endothelial growth factor receptor type 2 (sVEGFR2) were measured in 84 early BrC patients, both prior to surgery and within a median time of nine months post-treatment. Prognostic significance was evaluated using Kaplan-Meier survival and Cox regression analyses. Linear regression models were employed to examine the independent impact of selected angiogenic factors on DFS in breast cancer patients. The results of uni- and multivariate analyses indicated that a pre-treatment concentration of sVEGFR1 above 30.99 pg/mL was associated with improved disease-free survival (DFS) (p < 0.0001 for both analyses), while a pre-treatment concentration of sVEGFR2 above 9475.67 pg/mL was associated with an increased risk of BrC relapse (p < 0.0001 for both analyses). Additionally, a post-treatment concentration of sVEGFR2 above 7361.71 pg/mL was associated with better overall survival (OS) based on the Kaplan-Meier survival analysis (p = 0.0141). Furthermore, linear regression models revealed a significant inverse association between pre-treatment levels of sVEGFR1 and the risk of relapse (standardized β -0.2578, p = 0.0499) and a significant positive association of VEGF-A levels with the risk of recurrence (standardized β 0.2958, p = 0.0308). In conclusion, the findings suggest that both pre- and post-treatment levels of sVEGFR1 and sVEGFR2 may hold promise as potential prognostic markers for BrC patients.

The Association of Soluble VEGFR-1 Serum Level and Genetic (rs7993418) Polymorphism with In Vitro Fertilization and Embryo Transfer Outcome in the Population of Northern Iran.

Vascular endothelial growth factor receptors (VEGFRS) play an important role in embryo implantation. The aim of the present study was to examine the association of VEGFR1 circulating level and gene polymorphism with in vitro fertilization and embryo transfer (IVF-ET) outcome. In this case-control study, 120 women who had unsuccessful IVF (IVF-) history and 120 women who had successful IVF outcome (IVF+) as controls were included. Genomic DNA was extracted from blood samples. Genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The serum levels of soluble VEGFR1 (sVEGFR1) were measured by ELISA. ANOVA test was used for statistical analysis. The frequency of T and C alleles in IVF+ individuals were 87.5%, 12.5% and among IVF- were 75.5%, 24.5%, respectively (p=0.0006). The minor allele (C) was associated with an increased risk of IVF failure based on results from co-dominant (OR=3.86, 95%CI 1.19-12.47), dominant (OR=2.32, 95%CI 1.31-4.10), recessive (OR=3.22, 95%CI 1.00-10.29), and allele models (OR=2.28, 95%CI 1.40-3.69). We also showed that there is a significant decrease in serum sVEGFR1 levels in IVF as compared to IVF+ (p=0.006) groups. Moreover, TT genotype is significantly associated with increased serum sVEGFR1 concentration in IVF group (TT, CT, and CC serum levels were 106.55±11.04, 94.33±10.75, and 83.33±9.13 ng/ml, and in IVF+ group were 156.11±18.08, 120.66±16.51, and 84.66±20.31 ng/ml, respectively). The results of this study indicate that VEGFR1 polymorphism and sVEGFR1 circulating levels are associated with IVF-ET outcome. Moreover, CC genotype is associated with decreased sVEGFR-1 serum concentration and IVF-ET failure.

Pre-diagnostic levels of sVEGFR2, sTNFR2, sIL-2Rα and sIL-6R are associated with glioma risk: A nested case-control study of repeated samples.

No strong aetiological factors have been established for glioma aside from genetic mutations and variants, ionising radiation and an inverse relationship with asthmas and allergies. Our aim was to investigate the association between pre‐diagnostic immune protein levels and glioma risk. We conducted a case–control study nested in the Northern Sweden Health and Disease Study cohort. We analysed 133 glioma cases and 133 control subjects matched by age, sex and date of blood donation. ELISA or Luminex bead‐based multiplex assays were used to measure plasma levels of 19 proteins. Conditional logistic regression models were used to estimate the odds ratios and 95% CIs. To further model the protein trajectories over time, the linear mixed‐effects models were conducted. We found that the levels of sVEGFR2, sTNFR2, sIL‐2Rα and sIL‐6R were associated with glioma risk. After adjusting for the time between blood sample collection and glioma diagnosis, the odds ratios were 1.72 (95% CI = 1.01–2.93), 1.48 (95% CI = 1.01–2.16) and 1.90 (95% CI = 1.14–3.17) for sTNFR2, sIL‐2Rα and sIL‐6R, respectively. The trajectory of sVEGFR2 concentrations over time was different between cases and controls (p‐value = 0.031), increasing for cases (0.8% per year) and constant for controls. Our findings suggest these proteins play important roles in gliomagenesis.

Increased Plasma GDF15 Is Associated with Altered Levels of Soluble VEGF Receptors 1 and 2 in Symptomatic Multiple Myeloma

Introduction: In multiple myeloma, there is an increase in bone marrow microvascular density and enhanced renal lymphangiogenesis. Increased levels of the proangiogenic protein growth differentiation factor-15 (GDF15) have previously been reported to be associated with poor prognosis in myeloma. A possible association between GDF15 and the soluble forms of vascular endothelial growth factor receptors (sVEGFR) 1 and 2 has not yet been investigated, and a role for these receptors in pathological angiogenesis in myeloma is still to be defined. Methods: Plasma levels of GDF15 and sVEGFR1 and 2 were determined by ELISA in patients with smouldering multiple myeloma (sMM), patients with symptomatic multiple myeloma (abbreviated as MM), and healthy controls. The levels were compared between the three groups, and correlation coefficients were calculated, as were Kaplan-Meier curves for GDF15 and sVEGFR1 and sVEGFR2. Results: Levels of GDF15 were significantly higher in MM than in both patients with sMM and controls. A gradual decrease in mean sVEGFR1 concentration was observed, with MM > sMM > controls. Mean sVEGFR2 was lower in patients with MM than in controls. There was a positive correlation between GDF15 and sVEGFR1, and GDF15 correlated negatively with sVEGFR2. High GDF15 (>3 ng/mL) was associated with poor prognosis. Conclusion: In multiple myeloma, increased expression of GDF15 correlates positively with sVEGFR1 and negatively with sVEGFR2. It is possible that the altered levels of sVEGFR1 and 2 contribute to the increased angio- and lymphangiogenesis observed in myeloma.

SVEGFR1 Is Enriched in Hepatic Vein Blood-Evidence for a Provisional Hepatic Factor Candidate?

Background: Pulmonary arteriovenous malformations (PAVMs) are common sequelae of palliated univentricular congenital heart disease, yet their pathogenesis remain poorly defined. In this preliminary study, we used paired patient blood samples to identify potential hepatic factor candidates enriched in hepatic vein blood.Methods: Paired venous blood samples were collected from the hepatic vein (HV) and superior vena cava (SVC) from children 0 to 10 years with univentricular and biventricular congenital heart disease (n = 40). We used three independent protein analyses to identify proteomic differences between HV and SVC blood. Subsequently, we investigated the relevance of our quantified protein differences with human lung microvascular endothelial assays.Results: Two independent protein arrays (semi-quantitative immunoblot and quantitative array) identified that soluble vascular endothelial growth factor receptor 1 (sVEGFR1) is significantly elevated in HV serum compared to SVC serum. Using ELISA, we confirmed the previous findings that sVEGFR1 is enriched in HV serum (n = 24, p < 0.0001). Finally, we studied the quantified HV and SVC serum levels of sVEGFR1 in vitro. HV levels of sVEGFR1 decreased tip cell selection (p = 0.0482) and tube formation (fewer tubes [p = 0.0246], shorter tube length [p = 0.0300]) in vitro compared to SVC levels of sVEGFR1.Conclusions: Based on a small heterogenous cohort, sVEGFR1 is elevated in HV serum compared to paired SVC samples, and the mean sVEGFR1 concentrations in these two systemic veins cause pulmonary endothelial phenotypic differences in vitro. Further research is needed to determine whether sVEGFR1 has a direct role in pulmonary microvascular remodeling and PAVMs in patients with palliated univentricular congenital heart disease.

Levels of growth factors in the lungs affected by cancer with preventive effect of 1,3-diethylbenzimidazolium triiodide in the experiment

Purpose of the study. Analyzing the dynamics of VEGF-А, TGF-β and their receptors in the lung tissues in rats with antitumor effect of 1,3-diethylbenzimidazolium triiodide (Stellanin).Material and methods. The study included white outbred rats weighing 180–220 g. The main group included males (n=27) and females (n=27) with sarcoma 45 (s45) inoculated into the subclavian vein but not developed in the lungs (2×106 cells in 0.5 ml of saline) due to the subsequent intragastric administration of Stellanin (0.4 mg/kg once a day) according to an intermittent scheme: administration for 5 days and a break for 2 days. The control group included males (n=14) and females (n=14) without treatment with growing s45 in the lungs. Intact groups included 5 males and 5 females. After 4, 5 and 8 weeks of the experiment animals were decapitated, and levels of VEGF-A, sVEGF-R1, sVEGF-R2, TGF-β and sTGFβR2 were measured in 10% lung homogenates by ELISA (CUSABIO BIOTECH Co., Ltd., China).Results. Lung tissues of intact females showed 1.4 times (p&lt;0.05) lower VEGF-А and 3.3 times higher sVEGF-R1, compared to males. The development of tumors in all control rats was accompanied by the VEGF-А increase (by 1.6–3.0 times) and the TGF-β reduction (by 3 times). The dynamics of both VEGF receptors differed in males and females. The levels of sVEGF-R1 in males increased by 1.5 times (p&lt;0.05), while in females it decreased by 1.8 times (p&lt;0.05), and as a result, the levels became similar in all animals. The levels of sVEGF-R2 in males decreased by 2 times, and in females it increased by 1.4 times (p&lt;0.05), so the sVEGF-R2 content in females became 2.4 times higher than in males. In two-thirds of rats, Stellanin prevented s45 development in the lungs due to inhibition of VEGF-A growth by more than 2.0 times and an increase in concentrations of sVEGF-R1 by 10.0 times and TGF-β by 6.0 times, together with normalization of sVEGF-R2 and sTGFβR2.Conclusions. Stellanin prevents the development of malignant process in the lungs by inhibiting neoangiogenesis (deficiency of VEGF-A and excess of sVEGF-R1) and suppressing the proliferation of malignant cells (TGF-β growth).

Pretreatment to Posttreatment Hypoxia Inducible Factor-1α Ratios as a Potentially Predictive Marker for First-Line Treatment in Nonsmall Cell Lung Cancer Patients without Known Driver Mutations.

Background: Hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) are key angiogenic regulatory factors. The aim of this study was to identify the most useful prognostic angiogenic factors in advanced nonsmall cell lung cancer (NSCLC) without known driver gene mutations. Methods: Eligible patients were pathologically confirmed to have advanced NSCLC without known driver mutations. All patients were treated with standard first-line chemotherapy ± bevacizumab. Serum concentrations of HIF-1α, VEGF, sVEGFR1, sVEGFR2, and endostatin were measured via enzyme-linked immunosorbent assays (ELISAs) prior to and after two cycles of treatment. Area under the curve (AUC) and optimal cutoff values were calculated by receiver operator characteristic curve (ROC) analyses. The parameters that predicted survival were evaluated by univariate and multivariate Cox proportional hazard analyses. Results: A total of 47 patients were included in this study. HIF-1α levels decreased significantly after treatment in the nonprogressing (partial response/stable disease) patient group (707.94 vs. 355.53 pg/mL, p = 0.002), but increased levels were seen in patients with progressive disease, however, the extent of change did not reach significance (173.70 vs. 416.34 pg/mL, p = 0.078). An HIF-1α ratio of 1.18 was chosen as the best point to predict treatment response through ROC analyses. Via univariate and multivariate analyses, we found that patients with a HIF-1α ratio ≥1.18 after treatment were significantly more likely to have a prolonged progression-free survival (PFS, HR 0.303, 95% CI: 0.153-0.603, p = 0.001) and overall survival (OS, HR 0.436, 95% CI: 0.153-0.603, p = 0.025). Conclusions: We identified the pretreatment to posttreatment HIF-1α ratio as a promising predictor for PFS and OS in NSCLC patients without known driver mutations.

Abstract 13712: Association Between Soluble Vascular Endothelial Growth Factor Receptor-2 and Prognosis in Patients With Chronic Heart Failure: The PREHOSP-CHF Study

Introduction: Soluble vascular endothelial growth factor receptor-2 (sVEGFR-2) acts as an endogenous inhibitor of VEGF, a key regulator of angiogenesis and lymphoangiogenesis. However, little is known about the critical role of sVEGFR-2 in heart failure (HF). Methods: We performed a multicenter prospective cohort study (PREHOSP-CHF Study) to determine the predictive value of sVEGFR-2 for major adverse cardiovascular (CV) events (MACE) among patients with chronic HF (CHF). A total of 1,021 patients were included in the analyses. The mean age (SD) was 75.5 (12.6) years. 59.6% were male. The primary outcome was MACE defined as a composite of CV death or HF hospitalization. The secondary outcomes were all-cause death and CV death. Serum levels of sVEGFR-2 were determined employing specific enzyme-linked immunosorbent assays. Results: The patients with lower sVEGFR-2 concentrations were older, and had higher rates of female sex, atrial fibrillation and anemia. The baseline sVEGFR-2 level was inversely correlated with left ventricular ejection fraction, and was positively correlated with the body mass index. During the median follow-up of 730 days, a total of 210 (20.6%) all-cause deaths, 99 (9.7%) CV deaths and 308 (30.2%) HF hospitalizations occurred. Unadjusted Cox proportional hazard analyses revealed that the patients with the lowest quartile (Q1) of sVEGFR-2 did not show a significantly higher risk of MACE (p=0.7), but showed the greatest risks of CV death (p=0.003) and all-cause death (p=0.007). Even after adjusting for established risk factors and CV biomarkers (N-terminal pro-brain natriuretic peptide, contemporary sensitive cardiac troponin-I, and high-sensitivity C-reactive protein), those with the Q1 of sVEGFR-2 exhibited the greatest risk of CV death (p=0.02; hazard ratio [HR], 2.05; 95% confidence interval [CI], 1.17-3.66 [vs. Q2]; HR, 2.42; 95%CI, 1.30-4.68 [vs. Q3]; HR, 1.52; 95%CI, 0.80-2.99 [vs. Q4]), but not that of all-cause death. The sex-stratified analyses revealed that the association between sVEGFR-2 and CV death was still significant in men, but not in women (p for interaction, 0.07). Conclusions: A low sVEGFR-2 value was not associated with MACE, but was independently associated with CV mortality among patients with CHF.

Gene polymorphisms and serum levels of sVEGFR-1 in patients with systemic lupus erythematosus

Correlation between soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) concentration, VEGFR1 gene polymorphisms and systemic lupus erythematosus (SLE) risk remains unclear. The present case–control study comprised 254 SLE patients, 385 other rheumatic diseases patients and 390 healthy controls. Serum levels of sVEGFR-1 were detected by enzyme-linked immunosorbent assay. Seven VEGFR1 genetic variants (rs2296188, rs9943922, rs2296283, rs7324510, rs9554322, rs9582036, rs9554320) were genotyped by KASP. Serum levels of sVEGFR-1 were up-regulated in SLE and positively correlated with disease activity. Furthermore, serum sVEGFR-1 presented a distinctive elevation in SLE in comparison with other rheumatic diseases. Frequencies of allele T of rs2296283 and allele G of rs9554322 were significant lower in SLE patients (P = 0.003, P = 0.004). Frequencies of genotypes TT of rs2296188 and rs2296283 were declined in patients compared with healthy controls (P = 0.039, P = 0.033). CC genotype of rs7324510 and rs9582036 was negatively correlated with SLE risk (OR = 0.538, OR = 0.508). Distribution of GG, GC, GG + GC genotypes of rs9554322 were different between SLE patients and healthy controls (P = 0.027, P = 0.036, P = 0.010). Moreover, frequency of TC genotype of rs7324510 was higher in SLE patients with lupus headache (χ2 = 9.924, P = 0.039) and frequency of TC genotype of rs9943922 was lower in patients with cylindruriain (χ2 = 7.589, P = 0.026). Frequencies of allele C of rs7324510 and allele T of rs9943922 were decreased in SLE patients with cylindruria and hypocomplementemia, respectively (χ2 = 4.195, P = 0.041, χ2 = 3.971, P = 0.046). However, frequency of allele C of rs9554322 was increased in SLE patients with pyuria (χ2 = 11.702, P = 0.001). In addition, SLE patients carrying GG, GC, CC genotypes for rs9554322 had higher levels of serum sVEGFR-1. In conclusion, serum sVEGFR-1 was elevated in SLE patients and may be a disease marker. VEGFR1 gene polymorphisms related to risk of SLE in a Chinese Han population.

Association of High-Mobility Group Box-1 with Inflammationrelated Cytokines in the Aqueous Humor with Acute Primary Angle-Closure Eyes.

The aim of this study was to measure the levels of High-mobility group box-1 (HMGB1) and inflammation-related cytokines in the aqueous humor of patients with acute primary angle-closure glaucoma (APAG) and age-related cataract eyes (ARC). Aqueous humor samples were obtained from 59 eyes of 59 Chinese subjects (APAG, 32 eyes; and ARC, 27eyes). The multiplex bead immunoassay technique was used to measure the levels of HMGB1 and IL-8, IL-6, G-CSF, MCP-3, VEGF, sVEGFR- 1, sVEFGR-2, TNF-α, PDGF, and IL-10 in aqueous. The data of Patients' demographics and preoperative intraocular pressure (IOP) were also collected for detailed analysis. The APAG group showed significantly elevated concentrations of HMGB1, IL- 8, IL-6, G-CSF, VEGF, sVEGFR-1, and TNF-α than those in the ARC group. Aqueous HMGB1 level correlated significantly with IOP, IL-8, IL-6, G-CSF and sVEGFR-1 levels but not with age, TNF-α, or VEGF levels. The aqueous level of HMGB1 is elevated in APAG and associated with aqueous level of inflammation-related cytokines, suggesting an association between elevated levels of HMGB1, APAC and certain inflammatory modulators which, of course, should lead to further investigations in order to demonstrate the cause and effect.

Cytokine profiles in maternal serum are candidates for predicting an optimal timing for the delivery in early-onset fetal growth restriction.

We examined whether maternal serum cytokine profiles of mothers with early-onset fetal growth restriction (FGR) were associated with delivery within 2 weeks after sampling during the third trimester. This exploratory prospective cross-sectional study included a total of 20 singleton fetuses with early-onset FGR and 31 healthy controls. Maternal serum samples during the early third trimester were analyzed for 23 cytokines. Of 20 fetuses with early-onset FGR, 14 had delivery within 2 weeks after sampling. Multivariate analysis revealed that maternal serum concentrations of soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) and soluble CD40 ligand (sCD40L) were independently associated with delivery within 2 weeks in early-onset FGR. Among cases of early-onset FGR, concentrations of almost all maternal serum cytokines were similar. Maternal serum sVEGFR-1 concentrations were high when delivery occurred within 2 weeks. Maternal serum sCD40L concentrations were elicited only in cases in which delivery within 2 weeks occurred due to fetal deterioration. We identified two biomarkers, one specific for FGR and the other dependent on severity, that were significant components of angiogenic activities and inflammation factors. Imbalances in serum protein expression may have a substantial effect on the pathogenesis of FGR.

Effect of isotretinoin (13-cis-retinoic acid) on levels of soluble VEGF receptors (sVEGFR1, sVEGFR2, sVEGFR3) in patients with acne vulgaris

Background/aim The effect of isotretinoin on soluble VEGFRs has not been previously investigated. This study evaluate the effects of isotretinoin (13-cis-retinoic acid) on soluble VEGFR1 (sVEGFR1), soluble VEGFR2 (sVEGFR2) and soluble VEGFR3 (sVEGFR3). Methods The study included 38 patients (28 females, 10 males) receiving systemic isotretinoin treatment and 38 healthy individuals (28 females, 10 males) with similar age and gender characteristics. The blood samples of the patient group at third months and blood samples of the control group were compared in terms of sVEGFR1, sVEGFR2 and sVEGFR3 concentrations. Results It was significant that sVEGFR1 was low and sVEGFR3 was high in patients receiving isotretinoin (p: .038, p: .021, respectively). There was no significant change in sVEGFR2 levels between the groups (p: .519). Conclusions We think that the effect of isotretinoin on sVEGFR1, sVEGFR2 and sVEGFR3 may be secondary to its effects on the VEGF family. However, after clarifying the effect of isotretinoin on the VEGF family, we think that it can be used in some tumors and vascular diseases.

The Role of Angiogenesis Factors in the Formation of Vascular Changes in Scleroderma by Assessment of the Concentrations of VEGF and sVEGFR2 in Blood Serum and Tear Fluid.

Systemic sclerosis (SSc) is a connective tissue disorder characterized by tissue hypoxia, excessive fibrosis of skin and internal organs, and angiogenesis imbalance. The aim of the study was to evaluate in SSc patients the association between the retinal microcirculation disturbances and the presence of peripheral trophic changes and to determine the role of angiogenesis factors in the formation of vascular changes in scleroderma. Twenty-five SSc patients and 25 age- and sex-matched healthy controls were included to the study. Assay of vascular endothelial growth factor (VEGF) and soluble VEGF receptor-2 (sVEGFR-2) in blood serum and tears was done for all patients and controls using enzyme-linked immunosorbent assay. Retinal blood circulation was investigated with fluorescein angiography (FA) in the SSc patients only. In our research, proportion of mainly hypertensive patients presenting with a large spectrum of retinal microvascular lesions was 72%, while proportion of patients with skin microvascular lesions within distal phalanxes of fingers and toes was 76%. We noticed that patients with pathological changes in the FA examination had finger ulcerations significantly more often than patients without changes in the eye fundus. There were no statistically significant differences in the serum concentration of VEGF and sVEGFR2 between subjects in both analyzed groups. Analysis of lower levels of VEGF (p = <0.001) and sVEGFR-2 (p = <0.001) in blood serum accompanied by simultaneous higher levels of VEGF/sVEGFR-2 ratio in tears of SSc patients, as compared with the control group, indicates the superiority of proangiogenic factors in patients' tears.

MARKERS OF ANGIOGENESIS IN PATIENTS WITH ALOPECIA AREATA

This study was aimed to evaluate the level of production of angiogenesis markers, namely VEGF, sVEGFR1, EGF and NO system in 67 patients with alopecia areata, depending on the pathology severity and activity. The content of stable metabolites of NO (NO2 and NO3) and NOS was studied in blood plasma using a spectrophotometric method. Growth factors and sVEGFR1 were investigated in serum by solid enzyme−linked immunosorbent assay. At an active stage with a moderate to serious severity of alopecia areata, the VEGF value was significantly higher. In chronic course, the VEGF level was significantly decreased at all severity levels, but the minimum was observed in the patients with a severe stage. The most significant decrease in the concentration of sVEGFR1, an increase in the content of EGF was diagnosed at an active stage with a severe alopecia areata. With signs of disease progression to severe stage, the level of NO, NO3, iNOS was as high as possible. At a chronic stage, their significance was significantly reduced relative to secretion in active manifestations of the disease (p &lt; 0.01). In patients at an active stage with moderate and severe course of alopecia areata, the content of NO2 and cNOS was significantly lower than the level of indices at chronic disease. Correlation analysis revealed the existence of complex relationships between angiogenic factors, features of the disease course. Identified disorders can create conditions for the development of endothelial dysfunction and indicate a direct involvement of them into the mechanisms of formation of alopecia areata. Key words: alopecia areata, angiogenesis, endothelial dysfunction.

CHANGES OF ANGIOGENIC FACTORS AND MARKERS OF ENDOTHELIAL DYSFUNCTION IN CHILDREN AND ADOLESCENTS OF WILSON-KONOVALOV DISEASE

Although angiogenesis is an integral part of tumor progression, it has also been observed in different inflammatory, fibrotic, and ischemic diseases. Angiogenesis is a multifactorial process and its changes bring essential information about the status of complex pathology. Aim: evaluate the role of angiogenesis and endothelial dysfunction factors in Wilson-Konovalov disease (WKD) in children and adolescents. Methods: 19 children and adolescents with WKD were included in the study. VEGF-A, angiotensin (ANG), soluble receptors of VEGF-A (sVEGF-R1 и sVEGF-R2) and trombomodulin have been investigated in serum by enzyme immunoassay using special kits (BCM Diagnostics, USA). Other endothelial dysfunction markers as von Willebrand factor (vWf) was determined in blood plasma by immunoturbidimetry (Siemens, Germany), plasminogen (PLG) was investigated due to extended coagulation. Results: it was founded marked decreasing of VEGF-A and increasing concentration of sVEGF-R1, sVEGF-R2 in blood plasma of WKD children and adolescence by comparison of reference group. ANG did not change. Comparing the ratio of levels VEGF-A+ANG/sVEGF-R1+sVEGF-R2 (in children with WKD 16,7±1,9 and in reference group 23,0±1,6, р

Angiogenic parameters and the risk factors for thrombosis in polycythemia vera

Aim: The assessment of angiogenic parameters in so-called “liquid tumors”, such as myeloproliferative neoplasms, remains an open clinical issue. The aim of the study is to evaluate the concentration of vascular endothelial growth factor (VEGF-A) and soluble receptors sVEGFR-1 and sVEGFR-2 in relations to risk factors of thrombosis in patients with polycythemia vera (PV). Material/Methods: A total of 45 patients suffering from newly diagnosed PV and 30 healthy volunteers were enrolled into the study. Polycythemia vera was diagnosed according to the WHO (2008) criteria. In the citrated plasma samples VEGF-A, sVEGFR-1 and sVEGFR-2 were measured using ELISA tests. Results: VEGF-A concentration was three-fold higher and sVEGFR-2 significantly lower in PV patients as compared to the control group. VEGF-A concentration was significantly higher in PV patients with JAK2V617F mutation, as compared to patients without this mutation. SVEGFR-1 and sVEGFR-2 concentrations were similar in the analyzed subgroups. In PV patients with an increased number of white blood cells (WBCs), the above upper reference value (≥10 G/l), VEGF-A concentration was two-fold higher than in patients with WBCs number &lt;10 G/l. However, sVEGFR-1 and sVEGFR-2 concentrations did not differ between the analyzed subgroups. Analysis of correlations revealed only one relation between VEGF-A and WBCs number. Conclusions: Increased VEGF-A and decreased sVEGFR-2 concentrations in polycythemia vera patients as compared to the control group indicate an intensification of the process of angiogenesis. A higher concentration of VEGF-A in PV patients with leukocytosis and a positive correlation between WBCs number and VEGF-A reflect the potential role of VEGF-A in the pathogenesis of thrombotic complications in hypercoagulable state in PV patients.

Diagnostic Values of sVEGFR-1 and Endostatin in Malignant Pleural Effusions in Patients with Lung Cancer.

The diagnosis of malignant pleural effusion (MPE) remains a common clinical challenge because of the sensitivity of conventional cytology for the detection is insufficient. Thus, a sensitive clinical marker for diagnosis is required. The aim of this study was to assess the role of two anti-angiogenic cytokines, soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) and endostatin, in diagnosing MPE. Effusion samples from 44 patients with MPE caused by lung cancer and from 36 patients with benign pleural effusion (BPE) were collected. The concentrations of sVEGFR-1 and endostatin in pleural fluid were determined by an enzyme-linked immunosorbent assay (ELISA). The diagnostic performance was measured by receiver operating characteristic curves (ROCs). The levels of sVEGFR-1 and endostatin in MPE due to lung cancer were significantly higher than those in BPE (p < 0.05). The sensitivity and specificity of endostatin were 52.27% and 86.11%, respectively, while for sVEGFR-1, the sensitivity was 88.64% and the specificity was 58.33%. Interestingly, the combination of sVEGFR1 and endostatin produced better sensitivity and specificity of 72.73% and 83.33%, respectively. In addition, the levels of sVEGFR-1 and endostatin were significantly related to each other (p < 0.05), and the levels of endostatin in bloody effusions were significantly higher than those in non-bloody effusions (p < 0.05). Our study indicated that the levels of sVEGFR-1 and endostatin were significantly elevated in MPE. The combined detection of sVEGFR-1 and endostatin may be useful in the diagnosis of MPE.

VEGF-A, sVEGFR-1, and sVEGFR-2 in BCR-ABL negative myeloproliferative neoplasms

Background and objectiveData from the literature indicate the relationship between the bone marrow microvessel density and the blood parameters of angiogenesis. The aim of this study was to evaluate selected parameters of angiogenesis (VEGF-A, sVEGFR-1, and sVEGFR-2) and their correlations with white blood cells, platelets, and red blood cells. Materials and methodsThe study included 72 patients (mean age, 61.84 years) with myeloproliferative neoplasms (MPNs): essential thrombocythemia (ET) (n=46), polycythemia vera (PV) (n=19), and primary myelofibrosis (PMF) (n=7). Serum VEGF-A, sVEGFR-1, and sVEGFR-2 were determined using the ELISA assay. ResultsWe observed a significantly higher level of VEGF-A and reduced concentrations of sVEGFR-1 and sVEGFR-2 in the whole group of patients with MPNs as compared to controls. Detailed analysis confirmed significantly higher level of VEGF-A and lower concentration of sVEGFR-2 in each subgroups of MPNs patients. However, sVEGFR-1 concentrations were significantly lower only in PV and ET patients. ConclusionsThe study showed an increased level of VEGF-A, which may indicate the intensity of neoangiogenesis in the bone marrow. Decreased sVEGFR-1 and sVEGFR-2 in the blood of patients with MPNs may reflect consumption of these soluble receptors.

Overweight and obesity versus concentrations of VEGF-A, sVEGFR-1, and sVEGFR-2 in plasma of patients with lower limb chronic ischemia.

Being overweight or obese comprises a significant risk factor for atherosclerosis. Fat tissue also generates factors stimulating angiogenesis, the process by which new blood vessels form. The purpose of this paper is to assess concentrations of the vascular endothelial growth factor A (VEGF-A) and its soluble type-1 and type-2 receptors (sVEGFR-1 and sVEGFR-2) in plasma of patients with peripheral arterial disease (PAD) depending on the level of nutrition according to body mass index (BMI). The study group included patients suffering from symptomatic PAD (n=46) in Fontaine classes IIa-IV without any history of neoplastic disease and who have a normal BMI (n=15), are overweight (n=21) or are obese (n=10). The control group (n=30) consisted of healthy non-smoking volunteers who were neither overweight nor obese. Venous blood plasma samples were collected from both groups at rest in the morning to determine plasma concentrations of VEGF-A, sVEGFR-1, and sVEGFR-2 using the enzyme-linked immunosorbent assay (ELISA) method. The group of patients with PAD co-existent with being overweight or obese tended to have higher mean concentration levels of VEGF-A and sVEGFR-2 when compared with patients suffering from PAD with normal BMI. A statistically significant positive correlation was obtained between BMI and average plasma concentrations of sVEGFR-2 (R=0.37, P=0.0103). However, no significant correlation was noticed between BMI and VEGF-A or sVEGFR-1 concentrations. A positive correlation determined between the level of antiangiogenic factor and BMI value may be indicative of the linearly growing prevalence of some antiangiogenic factors in patients with metabolic disorders, which may be one of numerous factors contributing to incomplete efficiency of collateral circulation development in patients with PAD.