scholarly journals Vasoactive and Permeability Effects of Vascular Endothelial Growth Factor-165 in the Term in Vitro Dually Perfused Human Placental Lobule

Endocrinology ◽  
2007 ◽  
Vol 148 (10) ◽  
pp. 4734-4744 ◽  
Author(s):  
P. Brownbill ◽  
G. C. McKeeman ◽  
J. C. Brockelsby ◽  
I. P. Crocker ◽  
C. P. Sibley
Keyword(s):  
Nitric Oxide ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Vegf Receptor ◽  
Vascular Endothelial ◽  
Culture Techniques ◽  
Vasodilatory Effect ◽  
Endothelial Growth Factor ◽  
Maternal Side

Vascular endothelial growth factor (VEGF) is an important vasodilator and effector of permeability in systemic blood vessels. Molecular and tissue culture techniques have provided evidence for its placental synthesis and release. Using an in vitro dual-perfusion model of the term placental lobule from normal pregnancy, we report here the relative secretion of total VEGF, soluble VEGF receptor (VEGFR)-1, and free VEGF into the maternal and fetoplacental circulations of the placenta. We tested the hypothesis that VEGF has vasomotor and permeability effects in the fetoplacental circulation of the human placenta, and we examined the broad intracellular pathways involved in the vasodilatory effect that we found. We show that total VEGF is released into the fetal and maternal circulations in a bipolar fashion, with a bias toward maternal side output. Soluble VEGFR-1 was also secreted into both circulations with bias toward the maternal side. Consequently, free VEGF (12.8 ± 2.4 pg/ml, mean ± se) was found only in the fetoplacental circulation. VEGF-165 was found to be a potent vasodilator of the fetoplacental circulation (maximum response: 77% of previous steady-state fetal-side inflow hydrostatic pressure after preconstriction with U46619; EC50 = 71 pm). This vasodilatory effect was mediated by the VEGFR-2 receptor and nitric oxide in a manner-independent of the involvement of prostacyclin and the src-family tyrosine kinases. However, nitric oxide could explain only 50% of the vasodilatory effect. Finally, we measured the permeability of the perfused placenta to inert hydrophilic tracers and found no difference in the presence and absence of VEGF.

Vascular endothelial growth factor (VEGF) receptor-2 signaling mediates VEGF-CΔNΔC- and VEGF-A-induced angiogenesis in vitro

2003 ◽  
Vol 285 (2) ◽  
pp. 286-298 ◽  
Author(s):  
Jean-Christophe Tille ◽  
Xueyan Wang ◽  
Kenneth E Lipson ◽  
Gerald McMahon ◽  
Napoleone Ferrara ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Vegf Receptor ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor

Vascular endothelial growth factor (VEGF) is an autocrine growth factor for VEGF receptor–positive human tumors

Blood ◽  
2001 ◽  
Vol 98 (6) ◽  
pp. 1904-1913 ◽  
Author(s):  
Rizwan Masood ◽  
Jie Cai ◽  
Tong Zheng ◽  
D. Lynne Smith ◽  
David R. Hinton ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Tumor Cell ◽  
Cell Lines ◽  
Vegf Receptor ◽  
Vascular Endothelial ◽  
Autocrine Growth ◽  
Autocrine Growth Factor ◽  
Endothelial Growth Factor

Abstract Angiogenesis is required for the progression of tumors from a benign to a malignant phenotype and for metastasis. Malignant tumor cells secrete factors such as vascular endothelial growth factor (VEGF), which bind to their cognate receptors on endothelial cells to induce angiogenesis. Here it is shown that several tumor types express VEGF receptors (VEGFRs) and that inhibition of VEGF (VEGF antisense oligonucleotide AS-3) or VEGFRs (neutralizing antibodies) inhibited the proliferation of these cell lines in vitro. Furthermore, this effect was abrogated by exogenous VEGF. Thus, VEGF is an autocrine growth factor for tumor cell lines that express VEGFRs. A modified form of VEGF AS-3 (AS-3m), in which flanking 4 nucleotides were substituted with 2-O-methylnucleosides (mixed backbone oligonucleotides), retained specificity and was active when given orally or systemically in vitro and in murine tumor models. In VEGFR-2–expressing tumors, VEGF inhibition may have dual functions: direct inhibition of tumor cell growth and inhibition of angiogenesis.

Model of competitive binding of vascular endothelial growth factor and placental growth factor to VEGF receptors on endothelial cells

2004 ◽  
Vol 286 (1) ◽  
pp. H153-H164 ◽  
Author(s):  
Feilim Mac Gabhann ◽  
Aleksander S. Popel
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Endothelial Cells ◽  
Growth Factor ◽  
Synergistic Effects ◽  
Placental Growth Factor ◽  
Vegf Receptor ◽  
Vascular Endothelial ◽  
Relative Contribution ◽  
Endothelial Growth Factor

Placental growth factor (PlGF) competes with vascular endothelial growth factor (VEGF) for binding to VEGF receptor (VEGFR)-1 but does not bind VEGFR2. Experiments show that PlGF can augment the response to VEGF in pathological angiogenesis and in models of endothelial cell survival, migration, and proliferation. This synergy has been hypothesized to be due to a combination of the following: signaling by PlGF through VEGFR1 and displacement of VEGF from VEGFR1 to VEGFR2 by PlGF, causing increased signaling through VEGFR2. In this study, the relative contribution of PlGF-induced VEGF displacement to the synergy is quantified using a mathematical model of ligand-receptor binding to examine the effect on ligand-receptor complex formation of VEGF and PlGF acting together. Parameters specific to the VEGF-PlGF system are used based on existing data. The model is used to simulate in silico a specific in vitro experiment in which VEGF-PlGF synergy is observed. We show that, whereas a significant change in the formation of endothelial surface growth factor-VEGFR1 complexes is predicted in the presence of PlGF, the increase in the number of VEGFR2-containing signaling complexes is less significant; these results were shown to be robust to significant variation in the kinetic parameters of the model. Synergistic effects observed in that experiment thus appear unlikely to be due to VEGF displacement but to a shift from VEGF-VEGFR1 to PlGF-VEGFR1 complexes and an increase in total VEGFR1 complexes. These results suggest that VEGFR1 signaling can be functional in adult-derived endothelial cells.

Aspirin inhibits endothelial nitric oxide synthase (eNOS) and Flk-1 (vascular endothelial growth factor receptor-2) prior to rat colon tumour development

2004 ◽  
Vol 106 (1) ◽  
pp. 83-91 ◽  
Author(s):  
Marta ESCRIBANO ◽  
Laura MOLERO ◽  
Antonio LÓPEZ-FARRÉ ◽  
Cynthia ABARRATEGUI ◽  
Carolina CARRASCO ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Blood Vessels ◽  
Caspase 3 ◽  
Vegf Receptor ◽  
Vascular Endothelial ◽  
Colonic Tissue ◽  
Colon Tumour ◽  
Endothelial Growth Factor

Formation of blood vessels is a fundamental element in the control of tumour growth in which vascular endothelial growth factor (VEGF) and nitric oxide (NO) have been demonstrated to be involved. Our aim was to analyse whether changes in the expression of endothelial NO synthase (eNOS) and VEGF in colonic tissue could be detected early and even before the identification of colon tumour-associated morphological modifications in azoxymethane-treated rats. We studied further whether aspirin treatment changed these parameters. An increased expression of both eNOS and VEGF in colonic tissue from azoxymethane-treated rats compared with that from control rats was found. Aspirin treatment (10 mg/kg of body weight per day) reduced eNOS expression, but failed to modify the expression of VEGF in the colonic tissue of azoxymethane-treated rats. No evidence of aberrant crypt formation or changes in the number of blood vessels were observed in the colon of any of the animals studied. Expression of the VEGF receptor Flk-1, but not Flt-1, was increased in colonic tissue of azoxymethane-treated rats compared with control rats. The expression of Flk-1 was mainly localized in the epithelial cells, particularly in the lower part of the crypt. Aspirin treatment reduced Flk-1 expression in both control and azoxymethane-treated rats. Caspase-3 activity, which has been considered as an apoptotic index, was almost undetectable in azoxymethane-treated rats. Aspirin treatment stimulated caspase-3 activity. Overexpression of eNOS, VEGF and its receptor Flk-1 occurred early after azoxymethane administration in rat colonic tissue, even before morphological changes associated with tumour generation were observed, and aspirin prevented the overexpression of both eNOS and VEGF receptor Flk-1.

204 INADEQUACY OF VASCULAR ENDOTHELIAL GROWTH FACTOR IN CULTURE MEDIUM REDUCES THE VIABILITY OF CUMULUS CELLS AND PREVENTS IN VITRO MATURATION OF PORCINE OOCYTES

2016 ◽  
Vol 28 (2) ◽  
pp. 233
Author(s):  
T. T. M. Bui ◽  
P. P. Ferré ◽  
M. T. Tran ◽  
T. Wakai ◽  
H. Funahashi
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
In Vitro Maturation ◽  
Culture Medium ◽  
Adenosine Monophosphate ◽  
Cumulus Cells ◽  
Vegf Receptor ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor

Recently, vascular endothelial growth factor (VEGF) has been regarded as an important factor associated with not only follicle development but also meiotic competence of oocytes. However, the mechanism of how VEGF works is poorly understood. In this study, we investigated in vitro maturation (IVM) of oocytes from different sizes in the absence or presence of a VEGF receptor inhibitor, Axitinib. Cumulus-oocyte complexes (COC) were obtained from small follicles (SF; l < 3 mm in diameter) and medium follicles (MF; 3–6 mm in diameter). Each group of 30–40 COC with at least 3 layers of clear and compact cumulus cells (CC) was cultured in 500 μL of modified porcine oocyte medium (POM-β-mercaptoethanol) supplemented with 10 IU mL–1 eCG, 10 IU mL–1 hCG and 1mM dibutyryl-cyclic-adenosine monophosphate (dbc-AMP) for the first 20 h and then without those supplements for another 24 h at 39°C, 5% CO2 in air. During the first 20 h of IVM, culture medium was also supplemented with or without 1.25 nM Axitinib. At 20 h and 44 h after the start of IVM, the oocytes were denuded and stained with 4′6-diamidino-2-phenylindole (DAPI) to observe the nuclear stages. At 20 h after the start of IVM, some COC were also stained with PI and SYBR Green I to evaluate the ratio of live/dead cumulus cells. Statistical analyses of data from 5 replications were analysed by ANOVA and Tukey’s multiple comparison test. As compared with controls at 20 h after the start of IVM, the number of dead cumulus cells increased significantly in the groups treated with Axitinib, regardless of COC derived from MF and SF (16.8 v. 43.1% in MF and 25.3 v. 57.7% in SF, P < 0.01, respectively). At that time, a majority of oocytes from MF and SF remained at the germinal vesicle (GV) stage in controls (89.8 and 84.6%, respectively), but the percentage significantly reduced in the presence of Axitinib (57.9 and 48.9% of oocytes from MF and SF, respectively) and proceeded around the metaphase-I stage (37.5 and 44.8% of oocytes from MF and SF, respectively). At 44 h after the start of IVM, lower maturation rates were observed in oocytes treated with Axitinib than controls (35.0 v. 81.2% in MF; 20.1 v. 49.0% in SF; P < 0.01). In conclusions, VEGF plays an important role in maitaining the viability of cumulus cells. The presence of VEGFR inhibitor caused the oocytes to develop uncontrollably, even in the presence of dbc-AMP. Moreover, the deficiency of VEGF prevented oocytes fully competent to resume meiosis and arrest to metaphase II.

scholarly journals 6′-Sialylgalactose inhibits vascular endothelial growth factor receptor 2-mediated angiogenesis

2019 ◽  
Vol 51 (10) ◽  
pp. 1-13 ◽  
Author(s):  
Tae-Wook Chung ◽  
Eun-Yeong Kim ◽  
Hee-Jung Choi ◽  
Chang Woo Han ◽  
Se Bok Jang ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Mouse Model ◽  
Vascular Endothelial Cells ◽  
Fiber Formation ◽  
Vegf Receptor ◽  
Actin Stress Fiber ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor

Abstract Angiogenesis should be precisely regulated because disordered neovascularization is involved in the aggravation of multiple diseases. The vascular endothelial growth factor (VEGF)-A/VEGF receptor 2 (VEGFR-2) axis is crucial for controlling angiogenic responses in vascular endothelial cells (ECs). Therefore, inactivating VEGFR-2 signaling may effectively suppress aberrant angiogenesis and alleviate related symptoms. In this study, we performed virtual screening, identified the synthetic disaccharide 6′-sialylgalactose (6SG) as a potent VEGFR-2-binding compound and verified its high binding affinity by Biacore assay. 6SG effectively suppressed VEGF-A-induced VEGFR-2 phosphorylation and subsequent in vitro angiogenesis in HUVECs without inducing cytotoxicity. 6SG also inhibited VEGF-A-induced extracellular-regulated kinase (ERK)/Akt activation and actin stress fiber formation in HUVECs. We demonstrated that 6SG inhibited retinal angiogenesis in a mouse model of retinopathy of prematurity and tumor angiogenesis in a xenograft mouse model. Our results suggest a potential therapeutic benefit of 6SG in inhibiting angiogenesis in proangiogenic diseases, such as retinopathy and cancer.

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