Low Vascular Endothelial Growth Factor Research Articles

Influence of ovarian endometrioma on expression of steroid receptor RNA activator, estrogen receptors, vascular endothelial growth factor, and thrombospondin 1 in the surrounding ovarian tissues.

This study investigates the influence of ovarian endometrioma on expression of steroid receptor RNA activator (SRA), estrogen receptors (ERs), vascular endothelial growth factor (VEGF), and thrombospondin 1 (TSP-1) in the surrounding ovarian tissues. Taken from the women with ovarian endometrioma and mature teratoma during laparoscopy, the biopsies were analyzed by real-time polymerase chain reaction and Western blot. Our results indicated that ovarian tissues surrounding endometrioma had lower SRA and ER-α levels but higher SRA protein (SRAP) and ER-β levels than ovarian endometrioma. With lower VEGF levels and higher TSP-1 levels, the surrounding ovarian tissues showed higher expression levels of SRA, SRAP, ER-α, and ER-β in the ovarian endometrioma group when compared to the controls. These data showed that ovarian endometrioma increases SRA, ERs, and TSP-1 but decreases VEGF levels in the surrounding ovarian tissues, suggesting that abnormal expression of these molecules may affect biological behaviors of ovarian endometrioma.

Plasma levels of osteopontin and vascular endothelial growth factor in association with clinical features and parameters of tumor burden in patients with multiple myeloma.

The aim of this pilot study was to determine the plasma levels of osteopontin (OPN) and vascular endothelial growth factor (VEGF) and find possible association between them and main clinical features and parameters of tumor burden in patient with multiple myeloma (MM). Plasma levels of OPN and VEGF were determined in 44 newly diagnosed MM patients and 24 healthy persons by ELISA method. These values were compared with the presence of anemia, renal dysfunction, and bone lesions as myeloma related clinical manifestations and with serum beta-2 microglobulin and Durie-Salmon clinical stage as prognosticators related to tumor mass. The value of OPN was significantly higher in MM patients with evident bone lesions (P = 0.03) and there was also a positive correlation with serum beta-2 microglobulin (r = 0.366; P = 0.04). Furthermore, patients with lower Durie-Salmon stage had significantly lower OPN and VEGF levels (P = 0.05; P = 0.04, resp.). Our preliminary results found positive association between plasma level of OPN, tumor burden, and bone destruction. Further analysis should provide information about the possible use of OPN as useful clinical biomarker for monitoring bone disease and tumor mass, as well as a prognostic factor, or a possible target for pharmacological intervention.

Vascular Endothelial Growth Factor in Peritoneal Dialysis Patients

Vascular endothelial growth factor (VEGF) is a glycoprotein which exerts mitogenic effects on endo thelial cells, enhances neoangiogenesis and microvascular permeability, influences leukocyte kinetics when upreg ulated by hypoxia and high-glucose concentration in experimental conditions and in human pathology. Peritoneal synthesis of VEGF has been demonstrated in patients on peritoneal dialysis (PD) treated with glucose-based dialy sate solutions. The aim of the study was to determine the serum and peritoneal effluent VEGF concentrations in patients on chronic PD and to assess the relationship between age, gender, comorbidities, dialysis modality and vintage, therapy with erythropoiesis stimulating agents (ESA), angiotensin-converting enzyme inhibitors (ACEi) and statins and VEGF concentrations. Data on the use of ACEi, ESA, and statins were collected from patients' medical histories. VEGF was measured in serum and peritoneal effluent using the quantitative sandwich enzyme immunoassay (ELISA) kits (Quantikine® Human VEGF, R&D Systems, USA & Canada). Complete blood count and standard biochemical analyses (serum glucose, urea, creatinine, total protein, albumin, cholesterol, triglycerides, sodium, potassium, chloride, iron, total iron-binding capacity, ferritin, fibrinogen, C-reactive protein, and intact parathyroid hormone) were performed in fasting venous blood samples. Dialysis and residual components of Kt/V and normalized weekly creatinine clearance were calculated based on 24-hour urine and effluent collections. Peritoneal transport type was determined using the peritoneal equilibration test. Samples from 63 PD patients (39 males and 24 females, average age 61.97 ± 11.01 years) were analyzed. The average serum and effluent VEGF concentrations (231.84 ± 173.91 pg/mL and 38.39 ± 49.38 pg/mL, respectively) correlated significantly (p = 0.002). No significant difference was found in serum and effluent VEGF concentrations in relation to demographic characteristics, comorbidities, dialysis modality, therapy with ESA, ACEi, and statins. Patients treated with PD longer than 5 years had significantly higher serum VEGF levels (p < 0.05). Correlation analysis showed a statistically significant relationship between statin therapy and lower effluent VEGF concentration (p = 0.030). Serum VEGF concentration significantly correlated with fibrinogen serum concentration (p = 0.034) and glycemia (p = 0.004). Effluent VEGF concentration significantly correlated with cholesterolemia (p = 0.004). Serum VEGF concentrations were significantly higher in long term PD patients, and peritoneal effluent VEGF concentrations were significantly lower in patients receiving statins, suggesting a protective effect of those drugs on peritoneal membrane.

Protective effect of lycopene against diabetic retinopathy in rats and the related mechanism

Objective To study the protective effect of lycopene(LP)against diabetic retinopathy(DR)in rats and its related mechanism.Methods A single dose of streptozotocin(56mg/kg)was injected intraperitoneally in SD rats to induce diabetes retinopathy(DR),and the 20 successful DR models were equally randomized into DR group and LP treatment group.Meanwhile,10 normal rats served as normal control group(NC).LP group received LP gavage(60mg/kg)once a day;NC and DR groups were gavaged with equivalent saline daily for 8weeks.The serum levels of endothelin(ET)and calcitonin gene related protein(CGRP)were detected by using radioimmunoassay(RIA),and the expression of vascular endothelial growth factor(VEGF)in the retina was determined by immunohistochemistry and Western blotting analysis.Results The serum levels of ET and expression of VEGF in the retina were significantly increased in DR groups when compared with NC group(P0.05),and the serum CGRP was significantly decreased(P0.05);Compared with DR group,LP group had significantly lower VEGF expression and ET levels and significantly higher level of CGRP(P0.05).Conclusion LP can protect against DR in rats by decreasing serum ET,increasing serum CGRP,and subsequent down-regulating VEGF expression.

Expression of VEGF and Flk-1 and Flt-1 Receptors during Blood-Brain Barrier (BBB) Impairment Following Phoneutria nigriventer Spider Venom Exposure

Apart from its angiogenic and vascular permeation activity, the vascular endothelial growth factor (VEGF) has been also reported as a potent neuronal protector. Newborn rats with low VEGF levels develop neuron degeneration, while high levels induce protective mechanisms in several neuropathological conditions. Phoneutria nigriventer spider venom (PNV) disrupts the blood-brain barrier (BBB) and causes neuroinflammation in central neurons along with excitotoxic signals in rats and humans. All these changes are transient. Herein, we examined the expression of VEGF and its receptors, Flt-1 and Flk-1 in the hippocampal neurons following envenomation by PNV. Adult and neonatal rats were evaluated at time limits of 2, 5 and 24 h. Additionally, BBB integrity was assessed by measuring the expression of occludin, β-catenin and laminin and neuron viability was evaluated by NeuN expression. VEGF, Flt-1 and Flk-1 levels increased in PNV-administered rats, concurrently with respective mRNAs. Flt-1 and Flk-1 immunolabeling was nuclear in neurons of hippocampal regions, instead of the VEGF membrane-bound typical location. These changes occurred simultaneously with the transient decreases in BBB-associated proteins and NeuN positivity. Adult rats showed more prominent expressional increases of the VEGF/Flt-1/Flk-1 system and earlier recovery of BBB-related proteins than neonates. We conclude that the reactive expressional changes seen here suggest that VEGF and receptors could have a role in the excitotoxic mechanism of PNV and that such role would be less efficient in neonate rats.

Relationship between single nucleotide polymorphisms in the 3'-untranslated region of the vascular endothelial growth factor gene and susceptibility to diabetic peripheral neuropathy in China.

IntroductionThis study is to elucidate the relationship between a 936C/T mutation at the 3’-untranslated region of the human vascular endothelial growth factor (VEGF) gene and diabetic peripheral neuropathy (DPN).Material and methodsAll subjects recruited in this study were divided into DM (diabetes without neuropathy, retinopathy or nephropathy), DPN (diabetes with peripheral neuropathy only) and healthy control groups. The gene polymorphism was determined by polymerase chain reaction-restriction fragment length polymorphism, as well as other clinical methods including serum VEGF by ELISA.ResultsThe C allele frequency and CC genotype frequency in the DPN group were higher than those in the NC group and DM group. The T allele frequency and CT+TT genotype (carrying the T allele) frequency in the DPN group were lower than those in the NC group (χ2 = 19.051 and 18.533, both p < 0.001) and DM group (χ2 = 11.117 and 11.156, both p = 0.001). However, there was no statistically significant difference in the three genotype (CC/CT+TT) frequencies and allele (C/T) frequencies between the DM group and the NC group. The multivariate logistic regression analysis showed that the levels of glycated hemoglobin (HbA1c), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) and plasma VEGF positively correlated with DPN, while the 936C/T gene polymorphism of VEGF negatively correlated with DPN.ConclusionsAllele 936C of VEGF may serve as a genetic marker susceptible to DPN, while allele 936T may be a protective genetic marker of DPN.

EMP1 inhibits nasopharyngeal cancer cell growth and metastasis through induction apoptosis and angiogenesis

This study aimed to analyze the expression, clinical significance of epithelial membrane protein-1 (EMP1) in nasopharyngeal carcinoma, and the biological effect in its cell line by EMP1 overexpression. Immunohistochemistry and Western blot were used to analyze the EMP1 protein expression in 75 cases of nasopharyngeal cancer and 31 cases of normal tissues to study the relationship between EMP1 expression and clinical factors. Recombinant lentiviral vector was constructed to overexpress EMP1 and then infect nasopharyngeal cancer CNE2 cell line. Quantitative real-time RT-PCR and Western blot were used to detect the mRNA level and protein of EMP1. MTT assay, cell apoptosis, migration, and invasion assays were also conducted to determine the influence of the upregulated expression of EMP1 that might be found on CNE2 cells' biological effect. Immunohistochemistry and Western blot: The level of EMP1 protein expression was found to be significantly lower in nasopharyngeal cancer tissue than in the normal tissues (P < 0.05). Decreased expression of EMP1 was significantly correlated with T stages, lymph node metastasis, clinic stage, and histological grade of patients with nasopharyngeal cancer (P < 0.05). Meanwhile, the loss of EMP1 expression correlated significantly with poor overall survival time by Kaplan-Meier analysis (P < 0.05). The result of biological function has shown that CNE2 cell-transfected EMP1 had a lower survival fraction, higher cell apoptosis, significant decrease in migration and invasion, higher caspase-9, and lower vascular endothelial growth factor C protein expression compared with CNE2 cell-untransfected EMP1 (P < 0.05). EMP1 expression decreased in nasopharyngeal cancer and correlated significantly T stages, lymph node metastasis, clinic stage, histological grade, and poor overall survival, suggesting that EMP1 may play important roles as a negative regulator to nasopharyngeal cancer cell.

Circulating Endothelial Progenitor Cells Decrease in Infants with Bronchopulmonary Dysplasia and Increase after Inhaled Nitric Oxide

BackgroundImpairment of endothelial progenitor cells (EPCs) has been shown to contribute to the development of bronchopulmonary dysplasia (BPD). In the current study, the relationship between EPC changes of after birth and the development of BPD was investigated, and the effects of inhaled nitric oxide (iNO) on EPCs were evaluated.MethodsSixty infants with a gestational age of less than 32 weeks and a birth weight of less than 1500 g were studied. NO was administered to infants who were receiving mechanical ventilation or CPAP for at least 2 days between the ages of 7 and 21 days. EPC level was determined by flow cytometry at birth, 7, 21 and 28 days of age and 36 weeks’ postmenstrual age (PMA), before and after the iNO treatment. Plasma concentrations of vascular endothelial growth factor (VEGF), stromal cell-derived factor-1 and granulocyte-macrophage colony-stimulating factor were determined via immunochemical assay.ResultsTwenty-five neonates developed BPD, 35 neonates survived and did not develop BPD. EPC level was decreased on day 7 and 21 in infants who later developed BPD compared with infants that did not develop BPD. From birth to 21 days of age, BPD infants had a persistently lower VEGF concentration compared with non-BPD infants. No difference was found between the two groups at day 28 or 36 weeks PMA. In infants that later developed BPD, iNO raised the KDR+CD133+ and CD34+KDR+CD133+ EPC numbers along with increasing the level of plasma VEGF.ConclusionEPC level was reduced at 7 days of age in infants with BPD, and iNO increased the EPC number along with increasing the level of VEGF. Further studies are needed to elucidate the mechanism leading to the decrease of EPCs in infants with BPD and to investigate the role of iNO treatment in the prevention of BPD.

Prognostic implication of serum vascular endothelial growth factor in advanced hepatocellular carcinoma staging

Background. Staging systems have considerable impact on hepatocellular carcinoma (HCC) treatment approaches and outcomes. There is an unmet need to improve their stratification ability. We have evaluated four commonly used staging systems and assessed whether angiogenic biomarker vascular endothelial growth factor (VEGF) could improve their prognostic stratification.Material and methods. Four staging systems; Okuda, Cancer of the Liver Italian Program (CLIP), Barcelona Clinic Liver Cancer (BCLC), and Child-Pugh were evaluated in 78 HCC patients; their stratification abilities were detected by Kaplan-Meier curves and log-rank test; their accuracies of predicting survival were compared with the concordance index. Serum VEGF levels were measured using ELISA method. Recursive partitioning was used to determine the optimal VEGF cutoff. The prognostic significance of VEGF cutoff and other parameters were analyzed using univariate and multivariate models.Results. None of the staging systems demonstrated better discriminatory ability in predicting survival. The four staging systems did not reveal significant differences in probability of survival across their intermediate-advanced stages. Optimal cutoff identified for VEGF was 445 pg/mL. In advanced HCC, VEGF level (p = 0.004) and in early HCC, bilirubin level (p = 0.009) were identified as the independent prognostic factors. Survival comparison with high and low VEGF levels was significant for advanced HCC, while insignificant for early disease.Conclusion. Staging systems with conventional parameters did not provide good prognostic stratification for survival in advanced HCC population. Serum VEGF level was an independent predictor of survival in advanced HCC, and provided more survival homogeneity within the advanced stages of conventional staging systems.

Role of Activated Rac1/Cdc42 in Mediating Endothelial Cell Proliferation and Tumor Angiogenesis in Breast Cancer

Angiogenesis is a well-established target in anti-cancer therapy. Although vascular endothelial growth factor (VEGF)-mediated angiogenesis apparently requires the Rho GTPases Rac1 and Cdc42, the relevant mechanisms are unclear. Here, we determined that activated Rac1/Cdc42 in MCF-7 breast cancer cells could decrease p53 protein levels and increase VEGF secretion to promote proliferation and tube formation of human umbilical vein endothelial cells (HUVECs). However, these effects are reversed after ubiquitin-proteasome breakage. In exploring potential mechanisms for this relationship, we confirmed that activated Rac1/Cdc42 could enhance p53 protein ubiquitination and weaken p53 protein stability to increase VEGF expression. Furthermore, in a xenograft model using nude mice that stably express active Rac1/Cdc42 protein, active Rac1/Cdc42 decreased p53 levels and increased VEGF expression. Additionally, tumor angiogenesis was inhibited, and p53 protein levels were augmented, by intratumoral injection of the ubiquitin-proteasome inhibitor MG132. Finally in 339 human breast cancer tissues, our analyses indicated that Rac1/Cdc42 expression was related to advanced TNM staging, high proliferation index, ER status, and positive invasive features. In particular, our data suggests that high Rac1/Cdc42 expression is correlated with low wt-p53 and high VEGF expression. We conclude that activated Rac1/Cdc42 is a vascular regulator of tumor angiogenesis and that it may reduce stability of the p53 protein to promote VEGF expression by enhancing p53 protein ubiquitin.

Low Urine Vascular Endothelial Growth Factor Levels Are Associated with Mechanical Ventilation, Bronchopulmonary Dysplasia and Retinopathy of Prematurity

Background: Organ-specific vascular endothelial growth factor (VEGF) expression is decreased during the pathogenesis of bronchopulmonary dysplasia (BPD) and retinopathy of prematurity (ROP) several weeks before either disease can be diagnosed. Early measurement of organ-specific tissue VEGF levels might allow identification of infants at high risk for these diseases, but is not clinically feasible. Urine VEGF is easily measured and useful in early diagnosis of several diseases. Objectives: Our aims were to assess the correlation of urine VEGF levels measured in the first postnatal month with subsequent BPD or ROP diagnosis and to determine whether various infant characteristics influence urine VEGF levels. Methods: 106 subjects born at <29 weeks' gestation and surviving to 36 weeks' postmenstrual age were selected from an existing database and biorepository. Urine VEGF and total protein were measured in 2-3 samples per subject. Results: Urine VEGF/protein levels increased by 72% per week (p < 0.0001) during the first postnatal month. In multivariable analysis controlling for postnatal age, lower VEGF/protein was associated with higher levels of mechanical respiratory support (p = 0.006), male gender (p = 0.001) and early sepsis (p = 0.003) but not with fraction of inspired oxygen. Lower urine VEGF/protein and mechanical ventilation were each associated with BPD and ROP. In analyses adjusted for respiratory support, lower urine VEGF/protein and ROP remained associated but urine VEGF/protein and BPD did not. Conclusions: Low urine VEGF/protein levels in the first postnatal month are associated with mechanical ventilation, BPD, and ROP.

The vascular endothelial growth factor as a predictive and prognostic factor in patients with advanced gastric cancer treated with docetaxel, cisplatin, and 5-florouracil (DCF) regimen.

e15191 Background: Vascular endothelial growth factor (VEGF) is a key element stimulating the angiogenesis in solid tumors. In the current study, we aimed to assess the role of plasma VEGF levels as a prognostic and predictive marker for advanced gastric cancer patients treated with a modified docetaxel, cisplatinum and 5-florouracil (DCF) regimen. Methods: Thirty consecutive patients treated with a modified DCF regimen were included in the study. The plasma VEGF levels of the patients before treatment and following two cycles of chemotherapy were assayed. Results: The modified DCF regimen was well tolerated and yielded a median overall survival (OS) time of 9,0 months and 2-year OS rate of 20%. Good performance status, lower pre-treatment VEGF levels,and decrease in VEGF levels following chemotherapy were found to be independent prognostic factors for OS. Conclusions: The results of the current study suggest that the corrected plasma levels of VEGF could be used as a prognostic factor for advanced gastric cancer patients and a decrease in VEGF levels following 2 cycles of chemotherapy as a predictive marker for patients receiving DCF chemotherapy regimen.

A systematic review of vascular endothelial growth factor expression as a biomarker of prognosis in patients with osteosarcoma

Vascular endothelial growth factor (VEGF) plays an important role in the tumor angiogenesis, and its expression has been supposed to be a biomarker of prognosis in patients with osteosarcoma. There are many studies assessing the prognostic role of VEGF expression in osteosarcoma, and no consistent outcomes are reported. To provide a comprehensive assessment of the prognostic role of VEGF expression, we performed a systematic review and meta-analysis of published studies. We assessed the effect of VEGF expression on the overall survival rate and the disease-free survival rate by calculating the pooled odds ratio (OR) with corresponding 95 % confidence interval (95 %CI). Finally, 12 studies with a total of 559 osteosarcoma patients were included into the systematic review and meta-analysis. Compared with osteosarcoma patients with low or negative VEGF expression, patients with high VEGF expression were obviously associated with lower disease-free survival (OR=0.25, 95 %CI 0.11-0.58, P=0.001, I (2) =56.4 %). In addition, patients with high VEGF expression were obviously associated with lower overall survival (OR=0.22, 95 %CI 0.13-0.35, P<0.001, I (2) =0.0 %). Therefore, the findings from this systematic review suggest that VEGF expression is an effective biomarker of prognosis in patients with osteosarcoma.

Control of VEGF‐Endothelial Response by ECM Stiffness

Vascular endothelial growth factor (VEGF) drives both endothelial cell maintenance and normal/pathological angiogenesis. Recent research has suggested that mechanical signaling due to the stiffness of the cell contact surface may also have profound effects on endothelial cell behavior. To study VEGF signaling as a function of substrate stiffness, endothelial cells were cultured on fibronectin linked polyacrylamide gels and treated with VEGF. To analyze the response to VEGF we developed a custom MATLAB software script to analyze calcium flux movies. The script is able to individually identify cells, normalize each calcium signal value to the cell's individual background, and analyze the data. A variety of outputs are produced such as the magnitude of response, number of local maximums each cell experiences and clusters of coordinated cells. Utilizing this tool, we observed that VEGF‐stimulated intracellular calcium signaling varies in both magnitude and signaling kinetics depending on the stiffness of the substrate. At low VEGF concentrations we found maximal response (2–3.5 fold increases) at moderate stiffness whereas at high concentrations of VEGF the softest substrates showed the most intense response, but the response dissipated the fastest. We show that extracellular matrix stiffness can differentially drive endothelial response to VEGF. Supported by HL088572 and AHAF M2012014.

Diagnostic value of serum VEGF level for advanced cervical cancer and its relationship with therapeutic efficacy of concurrent chemoradiotherapy

Objective To investigate the diagnostic value of serum vascular endothelial growth factor (VEGF) level for cervical cancer and its relationship with the therapeutic efficacy of concurrent chemoradiotherapy (CCRT).Methods Eighty patients with a pathologically confirmed diagnosis of advanced cervical squamous cell carcinoma (CSCC),20 patients with chronic cervicitis,and 20 healthy persons (as controls) were enrolled in the study.The CSCC patients received CCRT.All the subjects had their baseline serum VEGF levels measured by enzyme-linked immunosorbent assay (ELISA);also,the CSCC patients had their serum VEGF levels measured by ELISA at 3 months after CCRT.The relationship between the serum VEGF levels and therapeutic efficacy of CCRT was analyzed.Results The CSCC patients had a significantly higher baseline serum VEGF level than the chronic cervicitis patients and controls (237.36 μg/L vs.142.36 μg/L,t =4.03,P =0.000).The serum VEGF level was closely related to tumor stage,tumor differentiation,and lymph node metastasis.A serum VEGF level above 197.52 μg/L was the optimal cut point for diagnosing cervical cancer,with a sensitivity of 0.88 and a specificity of 0.72.The serum VEGF levels before and after CCRT showed a close relationship with the therapeutic efficacy.The patients achieving a complete remission had a significantly greater change in serum VEGF level than those with progression; the patients with high baseline serum VEGF levels had a significantly higher tumor progression or death rate than those with low baseline serum VEGF levels.Conclusions Serum VEGF level has poor diagnostic value for cervical cancer,though it is closely related to the tumor stage,tumor differentiation,and lymph node metastasis of cervical cancer.However,serum VEGF level has some predictive value for the therapeutic efficacy of CCRT in patients with cervical cancer. Key words: Vascular endothelial growth factor; Related; Cervical neoplasms/radiochemotherapy

Expression of vascular endothelial growth factor (VEGF) and its receptors VEGFR1 and VEGFR2 in primary and recurrent WHO grade III meningiomas.

WHO grade III meningiomas are malignant neoplasms for which new and more targeted treatment strategies are urgently needed. Although clinical trials investigating anti-angiogenic vascular endothelial growth factor (VEGF) targeted therapies are currently recruiting, knowledge about the expression of VEGF and VEGF receptors remains to be determined. We investigated the expression of VEGF and its receptors VEGFR1 and VEGFR2 in 32 WHO grade III meningioma samples by immunohistochemistry. Furthermore, we performed in-situ hybridisation for VEGF. We found low VEGF expression in tumor and endothelial cells. Highest VEGF expression levels were seen in peri-necrotic tumor cells potentially suffering from hypoxia. VEGFR1 and 2 were virtually absent on tumor cells, although endothelial cells displayed significantly higher levels reaching stronger expression for VEGFR2 than VEGFR1. Our findings showing constant expression levels of VEGFR2 in endothelial cells serve as a first indication that the use of small tyrosine kinase inhibitors such as Sunitinib directly targeting the VEGF-receptors might be worth testing, also in the clinical context in cases of therapy-refractory meningiomas. Further investigations are needed to study the response to drugs targeting the VEGF pathway in relation to the expression profile of VEGF and its receptors in high grade meningiomas.

The role of VEGF and its soluble receptor VEGFR-1 in preterm newborns of preeclamptic mothers with RDS

Objective: We measured vascular endothelial growth factor (VEGF) and soluble VEGF receptor 1(sVEGFR-1) concentrations in cord blood and tracheal aspirate fluid (TAF) in order to investigate the role of them in lung maturation and the severity of respiratory distress syndrome (RDS) in preterm newborns, born to preeclamptic mothers.Methods: Newborns were divided into two groups as preterms born to preeclamptic mothers and preterms born to healthy mothers. They were also divided into two groups as severe RDS (sRDS) and mild RDS (mRDS) according to the need of surfactant and extent or type of ventilatory support. The concentrations of VEGF and sVEGFR-1 in cord blood and TAF (only in preterms with sRDS) were assayed by standardized enzyme-linked immunosorbent assay.Results: When the patients were evaluated as sRDS and mRDS, cord blood VEGF and VEGF/sVEGFR-1 concentrations of preterms with sRDS were significantly lower than the concentrations of preterms with mRDS. Conversely, cord blood sVEGFR-1 concentrations of preterms with sRDS were significantly higher than the concentrations of preterms with mRDS. VEGF and sVEGFR-1 concentrations in TAF could be compared only between sRDS preterms, born to preeclampsia (+) and (−) mothers. No statistical significance was detected between the two groups when sVEGFR-1, VEGF and VEGF/sVEGFR-1 concentrations in TAF were compared.Conclusion: Preeclampsia seems not to have an important effect on VEGF and sVEGFR-1 concentrations of preterm newborns both in cord blood and in TAF. Low VEGF and high sVEGFR-1 concentrations seem to be associated with the severity of RDS irrespective of preeclampsia, suggesting that VEGF may be one of the main components of lung maturation.

Neurovascular Unit and the Effects of Dosage in VEGF Toxicity: Role for Oxidative Stress and Thrombin

Bidirectional communication between neurons and vascular cells is important to the maintenance of the central nervous system (CNS) milieu. Vascular endothelial growth factor (VEGF), through its ability to affect both vascular and neuronal cells, is likely a key protein in this process. Despite considerable literature documenting a neuroprotective function for VEGF, overexpression of this protein has also been shown in a wide variety of CNS diseases, including Alzheimer's disease (AD). Increased oxidative stress and elevated thrombin levels have also been documented in AD, specifically in the microvasculature. The aim of the current study is to examine endothelial cells and neurons in vitro to determine the effects of oxidative stress and thrombin on VEGF release as well as the effects of low and high dose VEGF on neuronal viability. The data show that microvessels isolated from AD patients secrete significantly higher levels of VEGF compared to control-derived vessels. Exposure of brain endothelial cells to oxidative stress (sodium nitroprusside, menadione, or hydrogen peroxide) or thrombin significantly increases VEGF expression. Exposure of cultured neurons to oxidative stress increases expression of thrombin. Treating rat cortical neurons with high dose VEGF (≥500 ng/ml) decreases neuronal survival and expression of the anti-apoptotic protein Bcl-2 while increasing proapoptic proteins caspase 3 and phosphorylated p38 MAPK. High dose VEGF also negates the decrease in amyloid-β evoked by low dose VEGF. These results suggest that despite literature supporting neuroprotective effects of this protein, caution is warranted prior to implementation of VEGF as a therapeutic in the brain.

Serum Vascular Endothelial Growth Factor (VEGF-C) as a Diagnostic and Prognostic Marker in Patients with Ovarian Cancer

VEGF-C is regarded as one of the most efficient factors in regulating lymphangiogenesis. The aim of this study was to better understand the role of VEGF-C in the progression of ovarian cancer and to assess its diagnostic and prognostic significance. A total of 109 patients with ovarian cancer, 76 patients with benign ovarian diseases, and 50 healthy controls were recruited in this study. Serum levels of VEGF-C were determined by ELISA method. The results showed that serum levels of VEGF-C were significantly higher in the patients with ovarian cancer than those with benign ovarian diseases and healthy controls (P<0.01). Serum level of VEGF-C was correlated with FIGO stage, lymph node metastasis, tumor resectability, and survival of the patients (P<0.05). The areas of receiver operating curves of VEGF-C were higher than those of CA125 in different screening groups. Analysis using the Kaplan-meier method indicated that patients with high VEGF-C had significantly shorter overall survival time than those with low VEGF-C (P<0.0001). In a multivariate analysis along with clinical prognostic parameters, serum VEGF-C was identified as an independent adverse prognostic variable for overall survival. These results indicated that serum VEGF-C may be a clinically useful indicator for diagnostic and prognostic evaluation in ovarian cancer patients.

Effects of androgen on vascular and inflammatory biomarkers in a female hypertensive population

Background: Androgen is a steroid hormone associated with high blood pressure (BP). The effect of androgen on BP in females is unknown.Methods: Androgen, vascular endothelial growth factor (VEGF), interleukin (IL)-6 and matrix metalloproteinase (MMP)-9 were evaluated in females with menstruation disorders (n = 135, 28 ± 5 years old) and normal BP, pre-hypertension, stage 1 hypertension, and stage 2 hypertension.Results: Normal-BP (n = 57), pre-hypertension (n = 44), stage-1-hypertension (n = 21), and stage-2-hypertension (n = 13) females had similar androgen (3.3 ± 1.5, 2.7 ± 1.2, 3.1 ± 1.4, and 3.5 ± 1.3 ng/ml, p > 0.05) and IL-6 levels (1.7 ± 2.2, 1.9 ± 2.6, 1.3 ± 1.2 and 2.4 ± 3.3 pg/ml, p > 0.05). However, normal BP females had lower MMP-9 (609 ± 307 versus 891 ± 385 ng/ml, p < 0.05) than stage-1-hypertension females. In addition, normal BP females had lower VEGF (166 ± 103 versus 255 ± 139, 272 ± 128 and 301 ± 216 pg/ml, p < 0.05) than the other three groups. In normal-androgen females, VEGF levels were similar among the four groups. However, in high-androgen females, normal BP groups had lower VEGF levels than pre-hypertension, stage-1, and stage-2 hypertension groups (166 ± 94 versus 294 ± 153, 281 ± 160 and 357 ± 253 p < 0.05).Conclusions: Androgen can modulate growth factors and extracellular matrix proteins, which may contribute to the pathophysiology of hypertension in young females.