Difference In Vascular Endothelial Growth Factor Levels Research Articles

Anti-angiogenic effect of the combination of low-dose sorafenib and EGCG in HCC-induced Wistar rats

Background: Sorafenib is a standard drug used for advanced hepatocellular carcinoma but is often resistant and toxic. Its combination with epigallo-3-catechin gallate leads to reduced resistance and toxicity but an equally effective anti-angiogenic effect.Therefore, this study aims to assess the anti-angiogenic effect of standard-dose Sorafenib compared to the combination of low-dose Sorafenib and epigallo-3-catechin gallate. Methods: We conducted an animal study and double-blind, randomized controlled trials. A total of 25 male Wistar rats (7 weeks old) were randomly divided into four groups, namely Sham (K), Control (O), a combination of low-dose Sorafenib and epigallo-3-catechin gallate group (X1), and standard-dose Sorafenib group (X2). All groups were injected with N-Nitrosodiethylamine 70 mg/kg body weight (BW) intraperitoneally for ten weeks, except the Sham group. After the development of hepatocellular carcinoma, X1 and X2 were treated for two weeks. Subsequently, liver tissues and tumor masses were examined for vascular endothelial growth factor (VEGF) level and microvascular density expression. Results: There was a significant difference (p=0.007) in the level of VEGF between group X1 (low dose Sorafenib + EGCG) and X2 (Standard dose Sorafenib). However, the differences in VEGF levels of group X1 and X2 compared to group O(Control) were significantly lower, with values p=0.000136 and p=0.019, respectively. The expression of microvascular density between groups X1 and X2 was not entirely different. Meanwhile, a significant difference (p<0.05) was discovered when both groups were compared with the control group. Conclusion: The combination of low-dose Sorafenib with epigallo-3-catechin gallate is superior in reducing the level of VEGF compared to standard-dose Sorafenib and is better than the control. Standard-dose Sorafenib and the combination of low-dose Sorafenib and epigallo-3-catechin gallate have similar effectivity in reducing the expression of microvascular density and could prevent resistance and lower toxicity effects.

Anti-angiogenic effect of the combination of low-dose sorafenib and EGCG in HCC-induced Wistar rats.

Background: Sorafenib is a standard drug used for advanced hepatocellular carcinoma but is often resistant and toxic. Its combination with epigallo-3-catechin gallate leads to reduced resistance and toxicity but an equally effective anti-angiogenic effect.Therefore, this study aims to assess the anti-angiogenic effect of standard-dose Sorafenib compared to the combination of low-dose Sorafenib and epigallo-3-catechin gallate. Methods: We conducted an animal study and double-blind, randomized controlled trials. A total of 25 male Wistar rats (7-weeks-old) were randomly divided into four groups, namely Sham (K), Control (O), a combination of low-dose Sorafenib and epigallo-3-catechin gallate group (X1), and standard-dose Sorafenib group (X2). All groups were injected with N-Nitrosodiethylamine 70 mg/kg body weight (BW) intraperitoneally for ten weeks, except the Sham group. After the development of hepatocellular carcinoma, X1 and X2 were treated for two weeks. Subsequently, liver tissues were examined for vascular endothelial growth factor (VEGF) level and microvascular density expression. Results: There was a significant difference (p=0.007) in the level of VEGF between group X1 (low dose Sorafenib + EGCG) and X2 (Standard dose Sorafenib). However, the differences in VEGF levels of group X1 and X2 compared to group O(Control) were significantly lower, with values p=0.000136 and p=0.019, respectively. The expression of microvascular density between groups X1 and X2 was not entirely different. Meanwhile, a significant difference (p<0.05) was discovered when both groups were compared with the control group. Conclusion: The combination of low-dose Sorafenib with epigallo-3-catechin gallate is superior in reducing the level of VEGF compared to standard-dose Sorafenib and is better than the control. Standard-dose Sorafenib and the combination of low-dose Sorafenib and epigallo-3-catechin gallate have similar effectivity in reducing the expression of microvascular density and could prevent resistance and lower toxicity effects.

Vascular Endothelial Growth Factor Level in Patients With Oral Lichen Planus: A Systematic Review and Meta-Analysis

Background According to the possible role of vascular endothelial growth factor (VEGF) in the incidence of oral lichen planus (OLP) lesions, it seems necessary to evaluate this factor in patients with OLP. Objective The present study aims to investigate the level of VEGF in patients with OLP. Methods In this systematic review and meta-analysis, the search was conducted in online databases, including PubMed, Web of Science, and Scopus. The data were analyzed in the Stata v. 14 software at a 95% confidence interval (CI) and using a random effect model. The standardized mean difference was used to measure the difference in VEGF level between the two groups of control and OLP. The data heterogeneity was quantified by the I2 index. Results There was no significant difference between the two groups in terms of VEGF (SD=0.46, 95% CI: -2.13, -3.05, P=0.730) and the I2 index showed significant heterogeneity among the results of the studies (I2=97.9%). Based on the results of the immunohistochemistry, there was a significant difference in the VEGF level between the two groups (SD=3.30, 95% CI: 6.25, -0.36); however, the difference between the two groups was not statistically significant via the ELISA method (P=0.530). Conclusion The VEGF level in patients with OLP is higher compared to healthy people. Therefore, the serum factors which indicate VEGF should be considered an effective risk factor for OLP.

The Effect of Hypoxia Inducible Factor -1 Alpha and Vascular Endothelial Growth Factor Level in Type 2 Diabetes Microvascular Complications and Development.

Background:Angiogenesis in diabetic patients is often caused by hyperglycemia induced by hypoxiaObjective:The aim of this study was to analyze the serum level of Hypoxia Inducible Factor -1α (HIF-1α) and Vascular Endothelial Growth Factor (VEGF) between March until Desember 2020.Methods:This is a cross-sectional analytic methods, 135 patients with Type 2 Diabetes 48 samples with Microvascular complication and 87 samples with non-microvascular complication were recruited from the various primary health care centers in Medan city and surrounding areas in North Sumatera. VEGF levels and HIF-1α tested were done with ELISA methods in the laboratory of Medical Faculty, Universitas Sumatera Utara. Statistical analysis was performed using the IBM SPSS Statistics version 24. The significance level was set up to 0.005.Results:The median HIF-1 levels in patients with microvascular complications were lower than those without microvascular complications, with a range of HIF-1α values in non-complicated samples (0.02-13.96) ng/ml and a range of HIF-1α values in vascular complications (0.52- 8.87) mg/dL. There was a significant difference in HIF-1α levels in patients with Type-2 DM with complications compared to those without complications (p<0.05). Median VEGF levels were higher in complicated Type-2 DM. There was no difference in VEGF levels in patients with Type-2 DM with complications compared to those without complications (p > 0.005).Conclusion:HIF-1α and VEGF levels showed the development in vascularity. With the higher level of HIF-1α, an increase in VEGF levels were found, indicating the angiogenesis is occurring. Although complications have not yet occurred, it is predicted that high VEGF values will cause vascular complications in the future.

Vascular Endothelial Growth Factor Levels Difference among Hepatocellular Cancer Patients Based on Barcelona Clinic Liver Cancer Staging

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. It depends on angiogenesis for growth and metastasis. Vascular endothelial growth factor (VEGF), a growth factor for angiogenesis, is hoped to be a biomarker for the diagnosis of HCC and its development. AIM: The objective of the study is to determine the difference of VEGF levels among HCC patients based on barcelona clinic liver cancer (BCLC) staging. METHODS: A cross-sectional study was conducted at Haji Adam Malik General Hospital Medan, Indonesia between January and December 2018. Patients aged 18 years or older with HCC were enrolled using consecutive sampling method. Patients with cholangiocarcinoma, hemangioma, and liver metastasis were excluded from the study. The diagnosis of HCC was confirmed by triphasic computed tomography-scanning. Circulating VEGF levels were determined from serum specimen using Quantikine Human VEGF-enzyme-linked immunosorbent assay. All patients were grouped based on BCLC staging. Kruskal Wallis-H test was applied at 95% confidence interval. p &lt; 0.05 was considered significant. RESULTS: Of 60 patients, 47 (78.3%) were male. Mean age of patients was 61.4 (SD11.7) years. Hepatitis B was the most common etiology (70.0%) of HCC. Based on BCLC staging, 25 (41.7%) patients were in stage C. Median VEGF level was 951.25 pg/mL. There was a statistically significant difference in VEGF levels (p = 0.006) where patients in Stage C (1,009.6 pg/mL) and D (1,189.7 pg/mL) had higher VEGF levels compared to those in Stage A (578 pg/mL). CONCLUSION: There was a statistically significant difference of VEGF levels among HCC patients based on BCLC staging.

Changing of the vascular endothelial growth factor concentration in aqueous humor before and after intravitreal injection of Bevacizumab adjuvant treating complicated proliferative diabetic retinopathy

This article studies the changing of concentration of vascular endothelial growth factor (VEGF) from the aqueous humor sample, before and after intravitreal injection of Bevacizumab, for treatment of complicated proliferative diabetic retinopathy (PDR) and the correlation with clinical features. This study was implemented with prospective and interventional case series; 1.25 mg of Bevacizumab was injected into the vitreous cavity to treat PDRin 48 eyes of 29 patients. Aqueous humor samples were obtained before intravitreal injection of Bevacizumab and one week after. Study results showed: VEGF concentration decreased from 474.23±361.32 pg/ml to 16.96±18.11 pg/ml (p=0.000) at all eyes after one-week injection. There were no differences in levels of VEGF among groups according to the vitreous haemorrhage, tractional retinal detachment, and retinal fibrosis. Therefore, the study exhibited a better understanding of the role of anti-VEGF in the adjuvant treatment of complicated PDR.

Shared changes in angiogenic factors across gastrointestinal vascular conditions: A pilot study.

BACKGROUNDNeovascularisation is common to a variety of gastrointestinal (GI) disorders with differing aetiologies and presentations; usually affecting adults above 60 years. Shared angiogenic factors modulated by disease specific elements could be a common denominator and represent novel diagnostic and therapeutic targets. As yet, assessment of angiogenic factors across several GI vascular disorders associated with recurrent bleeding and anaemia has not been reported.AIMTo assess serum levels of angiogenic factors in several intestinal vascular disorders.METHODSA case control study was performed in Tallaght University Hospital in patients with endoscopically proven small bowel angiodysplasia (SBA), portal hypertensive gastropathy (PHG), gastric antral vascular ectasia (GAVE) and non-bleeding, non-anaemic controls. Using enzyme-linked immunosorbent assay, concentrations of Angiopoietin 1 (Ang-1), Ang-2 and vascular endothelial growth factor (VEGF) were measured from 2 serum tubes of blood following informed consent. The relative expression of Ang-1 and Ang-2 and Ang-1/2 ratio was calculated and compared between groups. Statistical analysis was applied using a t-test, and a P value of < 0.05 was considered significant.RESULTSTo date 44 samples were tested: 10 SBA, 11 PHG, 8 GAVE and 15 controls. Mean age 60 (range 20-85) years and 20 (45%) were males. Controls were significantly younger (49 years vs 66 years, P = 0.0005). There was no difference in VEGF levels between the groups (P = 0.6). SBA, PHG and GAVE Ang-1 levels were similar and were significantly lower than controls, (P = 0.0002, 95%CI: 241 to 701). Ang-2 levels were statistically higher in PHG and GAVE groups compared to controls (P = 0.01, 95%CI: 77.8 to 668) and as a result, also had a lower Ang-1/2 ratios compared to controls. While SBA Ang-2 levels were higher than controls, this did not reach statistical significance. Neither age nor haemoglobin level, which was similar between disease groups, could explain the difference. In addition, the median Ang-1/Ang-2 ratio for all patients was found to be significantly lower compared to controls, 8 vs 28 respectively, P = 0.001, 95%CI: -27.55 to -7.12.CONCLUSIONOur novel pilot study suggests common alterations in Ang-1 and Ang-2 levels across several GI vascular disorders. Differences in Ang-1/Ang-2 ratios among vascular disorders compared to controls suggest disease-specific modulation.

CSF VEGF Was Positively Associated with Neurogranin Independent of β-Amyloid Pathology.

PurposeIncreasing evidence suggests that both vascular endothelial growth factor (VEGF) and synaptic failure have been involved in the pathogenesis of Alzheimer’s disease (AD). However, it is not clear whether CSF VEGF levels are associated with synaptic function in living human.Patients and MethodsIn the present study, we included a total of 291 older individuals, including 83 individuals with normal cognition (NC), 143 individuals with mild cognitive impairment (MCI) and 65 patients with AD. Several linear regression models were conducted to examine the associations of CSF VEGF with CSF neurogranin levels (NG, reflecting synaptic degeneration) when controlling for other potential confounding factors, including age, gender, years of education, clinical diagnosis, APOE4 genotype and CSF β-amyloid 42 (Aβ 42) levels.ResultsThere was no significant difference in VEGF levels between the three diagnostic groups. In the pooled sample, females had significantly lower levels of VEGF than males. Aβ-positive (CSF Aβ 42 < 192 pg/mL) individuals had lower levels of VEGF than Aβ-negative individuals. However, the relationships between VEGF and NG levels were not modified by disease stage. Finally, we found that CSF VEGF levels were associated with NG levels with adjustment of age, gender, years of education, clinical diagnosis, APOE4 genotype and CSF Aβ 42 levels.ConclusionCSF VEGF levels were associated with NG independent of AD pathology and disease stage.

Abstract 104: Bio-functional Collagen Matrix Scaffold Composition Differentially Promotes Paracrine Activity In Human Induced Pluripotent Stem Cell Derived Vascular Smooth Muscle Cells

Purpose: Induced pluripotent stem cell-derived vascular smooth muscle cells (iPSC-VSMC) have the potential to treat chronic wounds by secreting proangiogenic factor vascular endothelial growth factor (VEGF) (1). However, little is known how the extracellular matrix (ECM) composition may impact the cells’ paracrine secretion profile. In this study, our objective was to understand the effects of ECM density and functionalities on the secretory profile of human iPSC-VSMCs. Methods: Type-I collagen was used as the material for the scaffolds and were incorporated with functional biomolecules: hyaluronic acid (HA), fibronectin, and laminin. This allowed fabrication of collagen scaffolds with different functionalities. The functionalities were used in combination with three different densities of type-I collagen (1.25mg/ml, 2.5mg/ml, and 5mg/ml) to study iPSC-VSMC viability and paracrine secretion profile. Several pro-angiogenetic factors included VEGF, SDF, PDGF, bFGF, angiopoietin 1, IL-8, and TGF-beta were investigated. The anti-inflammatory factor IL-10 was also evaluated. Results: Human iPSC-VSMCs embedded in collagen scaffolds containing functional biomolecules showed an increase in cell viability across all the collagen densities compared to the collagen scaffolds without functional biomolecules. The greatest significant level of cell proliferation was display by the 1.25mg/ml scaffolds (P-value=0.0001). Enhanced VEGF was observed in all three of the functionalized scaffolds at 1.25mg/ml collagen density (P value=0.0086) and also in the 2.5mg/ml collagen density scaffold containing HA (p value=0.0026), whereas no significant difference in VEGF level was found among 5mg/ml functionalized scaffolds. Interestingly, fibronectin-functionalized 5mg/ml collagen scaffold exhibited substantially elevated bFGF secretion (P value=0.0049). There was also a positive correlation between increasing amounts of fibronectin with increasing bFGF paracrine secretion (P value=0.0001). Furthermore, our data showed respective upregulation of IL-8 and IL-10 secretion in fibronectin-functionalized collagen scaffolds at the 1.25mg/ml and 2.5mg/ml collagen densities. Conclusion: These results suggested that functionalization along with density differentially regulate paracrine function of human iPSC-VSMCs. Future studies in elucidating the underlying signaling pathways and mouse model experiments will further deepen our understanding of the interaction between ECM and human iPSC-VSMCs. This will ultimately optimize human iPSC-VSMCs as a viable therapeutic agent for chronic wound healing. Reference: 1. Kuzuya M, Satake S, Esaki T, Yamada K, Hayashi T, Naito M, et al. Induction of angiogenesis by smooth muscle cell-derived factor: Possible role in neovascularization in atherosclerotic plaque. Journal of Cellular Physiology. 1995;164(3):658-67.

Effects of antibodies against human parvovirus B19 on angiogenic signaling.

Human parvovirus B19 (B19V) infection has symptoms similar to those of anti‑phospholipid syndrome(APS). Antibodies against B19V‑VP1 unique region(VP1u) exhibit activity similar to that of anti‑phospholipid antibodies(aPLs) by inducing vascular endothelial cell adhesion factors and APS‑like syndrome. Previous studies have identified an effect of aPLs on angiogenesis. However, little is understood regarding the effect of anti‑B19V‑VP1u antibodies on angiogenesis. The present study investigated the effects of anti‑B19V‑VP1u antibodies on the expression of adhesion molecules and angiogenic signaling using an aPL‑induced human umbilical vein endothelial cell(HUVEC) model, and trypan blue staining and western blotting. The effect of B19V‑VP1u antibodies on vascular endothelial growth factor(VEGF) expression in A549 cells, another well‑known model used to study angiogenesis, was also examined. Significantly higher intracellular adhesion molecule1 expression was observed following treatments with 10%fetal calf serum (FCS), aPL immunoglobulinG (IgG), B19V‑VP1u IgG or B19V‑NS1 IgG, compared with in the normal human (NH) IgG‑treated cells. Conversely, significantly higher vascular cellular adhesion molecule1 was only detected in HUVECs treated with B19V‑VP1u IgG. Significantly increased integrinβ1 was detected in HUVECs treated with aPLIgG or B19V‑VP1u IgG, whereas no difference in integrinβ1 was observed in those treated with 10%FCS, NH IgG or B19V‑NS1 IgG. No difference in AKT‑mTOR‑S6 ribosomal protein (S6RP) signaling was observed in HUVECs treated with B19‑VP1u IgG or B19V‑NS1 IgG, compared with NH IgG‑treated cells. Significantly higher human inducible factor‑1α was detected in HUVECs treated with 10%FCS, aPLIgG, B19V‑VP1u IgG or B19V‑NS1 IgG, compared with in NH IgG‑treated cells. However, there was no difference in the level of VEGF observed among HUVECs treated with NH IgG, B19V‑VP1u IgG or B19V‑NS1 IgG. Notably, no difference in VEGF level was observed in A549 cells treated with NH IgG, aPLIgG, B19V‑VP1u IgG or B19V‑NS1 IgG. These findings suggest that anti‑B19V‑VP1u antibodies may serve a role in activating adhesion molecules, but not in AKT‑mTOR‑S6RP signaling.

Mast cell mediators in relation to dengue severity: A systematic review and meta-analysis.

Degranulation of mast cells (MCs) releases several mediators such as vascular endothelial growth factor (VEGF), chymase, tryptase, histamine, and cytokines, which all have important roles in the severity of dengue infection. We aimed to investigate the role of MCs in severity of dengue. We searched for relevant studies in 10 databases on 15 August 2016. Meta-analysis (MA) was conducted by R version 3.5.0. We included 24 studies. in vivo and in vitro studies showed higher MC products released from infected mice/cells with dengue virus. In addition, when administering MC stabilizers or antihistaminic drugs, there was a decrease in vascular/capillary permeability. In human and at early stages, studies revealed an insignificant difference in VEGF levels in dengue fever (DF) versus dengue hemorrhagic fever (DHF) (standardized mean difference [SMD] 0.145; 95% confidence interval [CI], -0.348-0.638). Meanwhile, at acute stages and compared with healthy controls, high heterogeneity with an inconclusive difference in VEGF levels were noted in DF and DHF. However, pooled serum and plasma levels of VEGF were increased significantly in dengue shock syndrome (DSS) versus healthy controls (SMD 0.65; 95% CI, 0.3-0.95). There were also significantly higher chymase levels in DHF patients compared with DF during the acute phase (MD -6.531; 95% CI, -12.2 to -0.9). VEGF and chymase levels are mediators in dengue pathogenesis. However, limited data were available to support their role in severe dengue cases. Further studies are needed to evaluate the function of other mediators in dengue severity.

Association between Vascular Endothelial Growth Factor Plasma Levels and rs699947 Polymorphism and Coronary Collateral Vessel Formation

Background: The vascular endothelial growth factor (VEGF), as an angiogenic cytokine, binds endothelial cell receptors and stimulates angiogenesis and collateral formation. We evaluated the association between VEGF plasma levels and the gene polymorphism rs699947 and the formation of coronary collaterals in patients with coronary artery disease. Methods: A total of 195 patients with ≥70% narrowing in at least 1 coronary vessel (according to coronary angiography) were included in the study. The presence of the rs699947 polymorphism within the promoter of the VEGF gene was investigated using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The plasma VEGF concentration was quantified via the ELISA method. The Rentrop method was used to grade the extent of collateral development. Results: There was no significant difference in VEGF levels between the groups with good and poor collaterals. The frequency of the A allele of rs699947 was found to be higher in the patients with good collaterals than in those with poor collaterals (P=0.014). The odds ratio of good collaterals for AA was 2.67 (P=0.025) when compared with the CC genotype. Further, our additive model revealed an association between the rs699947 polymorphism and collateral formation (OR: 1.96, 95% CI: 1.05-3.65, P=0.033). Conclusion: The rs699947 polymorphism might be a novel genetic factor affecting collateral development in Iranian patients with coronary artery disease.

Vascular endothelial growth factor (VEGF) expression in induction phase chemotherapy of acute lymphoblastic leukemia

Background Leukemia is a hematolymphoid malignancy originating from bone marrow. The progression of hematolymphoid malignancies depends on new formation of vasculature, called angiogenesis. Angiogenesis is regulated by vascular endothelial growth factor (VEGF), which is secreted by paracrine and autocrine signaling mechanisms.&#x0D; Objective To evaluate VEGF expression in induction phase chemotherapy of acute lymphoblastic leukemia (ALL) patients. &#x0D; Methods This prospective, cohort study was conducted in ALL patients admitted to Dr. Wahidin Sudirohusodo Hospital, Makassar, South Sulawesi, from October 2016 to October 2017. Subjects’ VEGF levels were measured at diagnosis and at the end of induction chemotherapy.&#x0D; Results VEGF levels were analyzed in 59 patients, 29 of whom were diagnosed with standard risk ALL and 30 patients with high risk ALL. VEGF levels were significantly decreased after induction phase chemotherapy in standard risk ALL and in high risk ALL subjects. There was no significant difference in VEGF levels before induction phase chemotherapy between the standard and high risk groups (P=0.405). There was also no significant difference in VEGF levels after induction phase chemotherapy between the two risk groups (P=0.094).&#x0D; Conclusion The VEGF level is significantly lower after ALL induction phase chemotherapy in both the standard risk and high risk ALL groups. However, there are no significant differences in VEGF levels between the standard and high risk groups before as well as after induction phase chemotherapy.

S100A12 and vascular endothelial growth factor can differentiate Blau syndrome and familial Mediterranean fever from systemic juvenile idiopathic arthritis.

Systemic juvenile idiopathic arthritis (sJIA) has recently become regarded as one of the autoinflammatory syndromes (AIS). However, other AIS, such as familial Mediterranean fever (FMF) and Blau syndrome, have been initially misdiagnosed as sJIA because of the clinical similarities. Making the correct diagnosis in the early stage of these AIS is desirable. Therefore, we evaluated serum S100A12 and vascular endothelial growth factor (VEGF) levels to determine if they could be biomarkers for differentiating these AIS. Serum S100A12 and VEGF levels were examined in patients with Blau syndrome (n = 4), FMF (n = 4), and sJIA (n = 11) in the active and inactive phases. In the active phase, S100A12 levels were significantly higher in patients with sJIA and FMF compared with those with Blau syndrome (p < 0.001). VEGF levels of patients with sJIA were significantly higher than those of patients with others (p = 0.001). In the inactive phase, there was no significant difference in VEGF levels. However, colchicine-resistant patients or patients without treatment with FMF showed high levels of S100A12 compared with others. Measuring both serum S100A12 and VEGF levels may be useful for differentiating patients with Blau syndrome and FMF from those with sJIA at the early stage.

Efficacy of fumagillin bicyclohexylamine on experimental corneal neovascularization in rat model.

Fumagillin has been previously used to treat corneal microsporidial keratitis and also identified as an angiogenesis inhibitor. This study aimed to evaluate efficacy of fumagillin bicyclohexylamine on the rat model of corneal neovascularization induced by silver nitrate cauterization. Twenty-four Albino Wistar rats (n = 24) were divided into three groups. Following silver nitrate-induced corneal injury, eyes in Group 1 received one drop of 5mg/mL topical fumagillin bicyclohexylamine four times daily for 10days. Group 2 received subconjunctival injection of 0.1mL fumagillin bicyclohexylamine (2.5mg/mL) on day 1 and day 5. Group 3 received artificial tears and lubricants four times daily for 10days as control. On day 10, animals were sacrificed. Corneal specimens were obtained and prepared to assess vascular endothelial growth factor (VEGF-C) levels and corneal angiogenic microvessel density. There was no significant difference in VEGF-C levels between the groups (P = 0.994). Assessment of angiogenic microvessel density for peripheral corneal zone also did not reveal significant difference between the groups (P = 0.113). However, mean vascular density in Group 1 and Group 2 was significantly higher for both midperipheral and central corneal zones in comparison with Group 3 (P = 0.003, P = 0.015). Previously proved to be effective for treatment of microsporidial keratitis in humans, topical and subconjunctival concentration or dosing of fumagillin bicyclohexylamine failed to reduce corneal neovascularization induced by silver nitrate in this study. Further studies comparing different concentrations and dosing may detect inhibitory effects of fumagillin on corneal neovascularization without inducing toxicity.

Comparison of Vascular Endothelial Growth Factor Concentration in Porcine Kidneys Removed From Living Donors After Cardiac and Brain Death

The aim of this paper was to describe the differences in vascular endothelial growth factor (VEGF) concentration in porcine kidneys removed from living donors (group I), donors after prior induction of brain death by brain herniation (group II), and donors after cardiopulmonary arrest (group III). The groups consisted of 6 animals which underwent dual renal removal procedures; kidneys were rinsed, stored for 24 hours at 4°C and rinsed again. Renal specimens (4g) were collected before and after perfusion (time 0 and 1), after 12 hours (time 2), and after reperfusion (time 3). A Western blot was used to evaluate VEGF concentration in collected tissues homogenates. Additionally, the levels of VEGF, interleukin 1β, tumor necrosis factor α, and endothelial nitric oxide synthase (eNOS) were detected with enzyme-linked immunosorbent assays. Directly after the removal procedure, no significant differences in VEGF levels (IOD) were observed depending on the donor (moderate levels were observed in all groups: 1.51 in group I, 1.48 in group II, and 1.35 in group III). As a consequence of perfusion and 12 hours of storage, a stable concentration in groups I and III was observed with a gradual increase of VEGF levels in group II (1.23, 2.08, and 1.67 in the respective groups at time 1; 1.49, 2.12, and 1.63 in the respective groups at time 2). After the following 12 hours, a statistically significant (P < .05) higher level of VEGF was observed in group II (2.34) in comparison to groups I and III (1.58 and 1.81, respectively). In group I, a correlation between VEGF concentration and IL-1β was observed, while in group II there was correlation between VEGF and eNOS levels.

Lipid levels and selected biomarkers of vascular changes in children with idiopathic headaches - a preliminary report.

IntroductionElevated lipid concentrations were observed in adults with headaches. However, studies in children are scarce. Recent data suggest new potential risk factors for atherosclerosis, which may be associated with headaches. The aim of the study was to analyse the blood levels of lipids and new markers of atherosclerosis in children with idiopathic headaches.Material and methodsThe study population comprised 65 children (39 with idiopathic headaches and 26 healthy children). Total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL) cholesterol and triacylglycerol (TG) levels were measured in every patient. Brain-derived neurotrophic factor (BDNF), soluble CD40 ligand (sCD40L), endothelial plasminogen activator inhibitor (serpin E1/PAI I) and vascular endothelial growth factor (VEGF) blood level measurements were performed in 34 children.ResultsChildren with headaches had higher BMI z-scores (0.2 vs. –1.14; p = 0.006). TC level was lower in patients with headaches (121.04 mg/dl vs. 146.87 mg/dl, p = 0.019). No differences in concentrations of TG, HDL or LDL were found. BDNF was significantly higher in the studied group (171.57 pg/ml vs. 64.04 pg/ml, p = 0.012). The VEGF was higher in boys with headaches than in girls (368.27 pg/ml vs. 142.86 pg/ml, p = 0.011). There were no differences in levels of VEGF, sCD40L or PAI-1 between groups.ConclusionsChildren with headaches have lower total cholesterol and higher BDNF levels than controls. No significant difference in levels of triacylglycerols, HDL cholesterol, LDL cholesterol, VEGF, sCD40L or PAI-1 was found between children with headaches and controls.

Effect of erythropoietin stimulating agents on vascular endothelial growth factor levels in patients with end stage renal disease.

End stage renal disease (ESRD) is a debilitating disease that not only impacts quality of life, but also increases the risk of cardiovascular disease, stroke, and overall mortality. By improving our understanding of the molecular patterns seen in progression of chronic renal disease (CRD), we may be able to slow down and possibly even prevent progression renal failure. The vascular endothelial growth factor (VEGF) has been implicated as a major contributor to CRD disease progression, thus our aim was to profile the VEGF levels in patients with ESRD and to determine the effects of the erythropoietin stimulating agents (ESAs). Under institution review board (IRB) approval, plasma samples were collected from 77 patients prior to hemodialysis and heparin administration. Normal human plasma samples (female & male, 18-35 years old) were purchased from George King Biomedical Inc (Overland Park, KS). All samples were stored at -80 °C. Inflammatory biochips were purchased from RANDOX (Co. Antrim, Northern Ireland) to test VEGF on 77 ESRD and 48 normal samples. The VEGF was significantly elevated in ESRD vs. normal (P<0.0001), ESRD+ESA vs. normal (P<0.0001), and ESRD-ESA vs. normal (P<0.0001). No difference was seen between ESRD+ESA and ESRD-ESA. Hemoglobin and free iron were significantly elevated in ESRD-ESA compared to ESRD+ESA (PHemoglobin=0.0007, PIron<0.0001). Our finding that VEGF was significantly elevated in ESRD vs. normal, aligns with the literature and suggests that VEGF may in fact play a key role in CRD progression. However, further studies to evaluate VEGF isomer levels are needed. While we saw lack of difference in VEGF levels between ESRD+ESA and ESRD-ESA, this may be due to the treatment algorithm used. Further investigation is warranted to determine whether the ESAs and hemoglobin levels show any influence on or crosstalk with the VEGF levels.

Clinical significance of serum vascular endothelial growth factor in young male asthma patients.

Background/AimsVascular endothelial growth factor (VEGF) is an important mediator of angiogenesis. However, little is known about the potential use of serum levels of VEGF as a biomarker for asthma. We investigated the differences in VEGF levels among normal controls, stable asthma patients, and those with exacerbation of acute asthma. All subjects were young males.MethodsWe measured VEGF levels in each patient group, and examined any serial changes in those with acute exacerbation.ResultsVEGF levels were significantly higher in stable asthmatic patients and even more so in acute asthmatic patients, compared to healthy controls. However, there was no correlation between VEGF levels and forced expiratory volume in 1 second in patients with stable asthma. In addition, there were no correlations between VEGF levels and asthma control test scores. In patients with acute exacerbation, VEGF levels significantly increased during the acute period; their levels decreased gradually at 7 and 14 days after treatment.ConclusionsCompared to normal control patients, the serum levels of VEGF were elevated in stable asthma patients and even more elevated in patients with acute exacerbation. However, the role of VEGF as a biomarker in stable asthma is limited. In patients with acute exacerbation, VEGF levels were associated with clinical improvements.

Does VEGF facilitate local tumor growth and spread into the abdominal cavity by suppressing endothelial cell adhesion, thus increasing vascular peritoneal permeability followed by ascites production in ovarian cancer?

BackgroundOvarian cancer is mostly associated with pathologically regulated permeability of peritoneal vessels, leading to ascites. Here, we investigated the molecular regulation of endothelial permeability by the vascular endothelial growth factor (VEGF) and both tight and adherens junction proteins (VE-cadherin and claudin 5) with regards to the tumor biology of different ovarian cancer types.MethodsSerum and ascites samples before and after surgery, as well as peritoneal biopsies of 68 ovarian cancer patients and 20 healthy controls were collected. In serum and ascites VEGF protein was measured by ELISA. In peritoneal biopsies co-localization of VE-cadherin and claudin 5 was investigated using immunohistochemical dual staining. In addition, the gene expression of VE-cadherin and claudin 5 was quantified by Real-time PCR. Differences in VEGF levels, VE-cadherin and claudin 5 gene expression were analyzed in relation to various tumor characteristics (tumor stage, grading, histological subtypes, resection status after surgery) and then compared to controls. Furthermore, human primary ovarian cancer cells were co-cultured with human umbilical vein endothelial cells (HUVEC) and changes in VE-cadherin and claudin 5 were investigated after VEGF inhibition.ResultsVEGF was significantly increased in tumor patients in comparison to controls and accumulates in ascites. The highest VEGF levels were found in patients diagnosed with advanced tumor stages, with tumors of poor differentiation, or in the group of solid / cystic-solid tumors. Patients with residual tumor after operation showed significantly higher levels of VEGF both before and after surgery as compared to tumor-free resected patients. Results of an immunohistochemical double-staining experiment indicated co-localization of VE-cadherin and claudin 5 in the peritoneal vasculature. Compared to controls, expression of VE-cadherin and claudin 5 was significantly suppressed in peritoneal vessels of tumor patients, but there were no significant differences regarding VE-cadherin and claudin 5 expression in relation to different tumor characteristics. A significant positive correlation was found between VE-cadherin and claudin 5 expression. VEGF inhibition in vitro was associated with significant increase in VE-cadherin and claudin 5.ConclusionsOur results indicate that increased peritoneal permeability in ovarian cancer is due to down-regulation of adhesion proteins via tumor derived VEGF. Advanced ovarian cancer with aggressive tumor biology may be associated with early dysregulation of vascular permeability leading to ascites. These patients may benefit from therapeutic VEGF inhibition.