Correlation of vascular endothelial growth factor messenger RNA expression with peritumoral vasogenic cerebral edema in meningiomas

1996 ◽  
Vol 85 (6) ◽  
pp. 1095-1101 ◽  
Author(s):  
Steven N. Kalkanis ◽  
Rona S. Carroll ◽  
Jianping Zhang ◽  
Amir A. Zamani ◽  
Peter McL. Black
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Messenger Rna ◽  
Vascular Endothelial ◽  
Peritumoral Edema ◽  
Vegf Mrna ◽  
Content Type ◽  
Endothelial Growth Factor ◽  
Vegf Mrna Expression ◽  
Fine Print

✓ Intracranial meningiomas are often complicated by peritumoral vasogenic cerebral edema, which appears to result from increased microvascular permeability and extravasation of proteinaceous and plasma fluid into the adjacent peritumoral space. The source of such edema has long been mysterious. The contents of this paper support the concept that vascular endothelial growth factor (VEGF) production plays a significant role in edema formation. Vascular endothelial growth factor messenger RNA expression has been found in a wide range of intracranial neoplasms, including malignant gliomas, metastatic melanomas, meningiomas, and other benign tumors. Several studies have confirmed the importance of VEGF in tumorigenesis, neovascularization, and edema production. This study tests the hypothesis that the presence of peritumoral edema in meningiomas is positively correlated with increased expression of VEGF mRNA. To investigate this hypothesis, 31 meningioma specimens were subjected to Northern blot analysis, hybridization with a complementary DNA VEGF probe, and laser densitometry to determine the relative levels of VEGF mRNA expression. Magnetic resonance imaging was then used in a double-blind fashion to correlate the neuropathological tissue samples with the presence of preoperative peritumoral edema. Of 31 patients studied, 14 exhibited no edema and 17 exhibited some level of peritumoral fluid accumulation. There was a marked increase in VEGF expression in patients with edema (p = 0.0004, Wilcoxon-Mann-Whitney rank-sum test). Meningiomas with peritumoral edema exhibited 3.4 times the level of VEGF mRNA as those without edema. These data demonstrate a strong link between VEGF mRNA expression and peritumoral edema and indicate that VEGF expression is an important factor in the etiology of edema around meningiomas.

scholarly journals Vascular endothelial growth factor increases messenger RNAs encoding cyclooxygenase-II and membrane-associated prostaglandin E synthase in rat luteal cells

2004 ◽  
Vol 183 (3) ◽  
pp. 527-533 ◽  
Author(s):  
T Sakurai ◽  
K Tamura ◽  
H Kogo
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Mrna Expression ◽  
Corpus Luteum ◽  
Prostaglandin E ◽  
Vascular Endothelial ◽  
Vegf Mrna ◽  
Luteal Cells ◽  
Endothelial Growth Factor ◽  
Vegf Mrna Expression

Vascular endothelial growth factor (VEGF) is known to be necessary for the vascularization of the developing corpus luteum. Our recent data suggested that cyclooxygenase-II (COX-II) may play a role in the formation of vascular plexuses in developing corpora lutea of the rat. Here we examined the relationship between VEGF and the expression of prostaglandin (PG)- metabolizing enzymes in rat ovarian luteal cells. VEGF treatment caused a dose-dependent increase in the expression of COX-II and membrane-associated PGE synthase (mPGES) mRNA in cultured rat luteal cells. However, pretreatment of the luteal cells with a selective COX-II inhibitor, NS-398, abolished the VEGF-enhanced mPGES mRNA expression. VEGF also increased PGE2 secretion. Conversely, PGE2 dose-dependently stimulated VEGF mRNA expression. Furthermore, VEGF induced VEGF mRNA expression, but this effect was abolished by NS-398 pretreatment. These findings suggest that VEGF enhances PGE2 production by stimulating COX-II and mPGES expression in rat corpus luteum and that the effect of VEGF on luteal cells may be partially mediated by this stimulation of PGE2 production.

scholarly journals Antagonistic Functions of Tetradecanoyl Phorbol Acetate-Inducible-Sequence 11b and HuR in the Hormonal Regulation of Vascular Endothelial Growth Factor Messenger Ribonucleic Acid Stability by Adrenocorticotropin

2006 ◽  
Vol 20 (4) ◽  
pp. 916-930 ◽  
Author(s):  
Nadia Cherradi ◽  
Cyrille Lejczak ◽  
Agnes Desroches-Castan ◽  
Jean-Jacques Feige
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Nuclear Export ◽  
Mrna Levels ◽  
Vascular Endothelial ◽  
Vegf Mrna ◽  
Adrenocortical Cells ◽  
Tetradecanoyl Phorbol Acetate ◽  
Endothelial Growth Factor ◽  
Vegf Mrna Expression

Abstract Expression of vascular endothelial growth factor (VEGF), an endothelial cell-specific mitogen and a potent angiogenic factor, is up-regulated by a variety of factors including hypoxia, growth factors, and hormones. In the adrenal cortex, regulation of VEGF expression by the pituitary hormone ACTH ensures the maintenance of the organ vasculature. We have previously shown that ACTH evokes a rapid and transient increase in VEGF mRNA levels in primary adrenocortical cells through transcription-independent mechanisms. We further demonstrated that the zinc finger RNA-binding protein Tis11b (tetradecanoyl phorbol acetate-inducible-sequence 11b) destabilizes VEGF mRNA through its 3′-untranslated region (3′-UTR) and that Tis11b is involved in the decay phase of ACTH-induced VEGF mRNA expression. In the present study, we attempted to determine the mechanisms underlying ACTH-elicited increase in VEGF mRNA levels in adrenocortical cells. We show that ACTH triggers an increase in the levels of the mRNA-stabilizing protein HuR in the cytoplasm and a concomitant decrease in the levels of HuR in the nucleus. This process is accompanied by an increased association of HuR with the nucleocytoplasmic shuttling protein pp32, indicating that ACTH induces HuR translocation from the nuclear to the cytoplasmic compartment. Leptomycin B, a specific inhibitor of CRM1-dependent nuclear export of pp32, significantly reduced ACTH-induced VEGF mRNA levels. Furthermore, RNA interference-mediated depletion of HuR in adrenocortical cells abrogated ACTH-induced VEGF mRNA expression. Finally, we show that Tis11b and HuR exert antagonistic effects on VEGF 3′-UTR in vitro. Although both proteins could bind simultaneously on VEGF 3′-UTR, Tis11b markedly decreases HuR-binding to this RNA sequence. Altogether, these results suggest that the RNA-stabilizing protein HuR is instrumental to ACTH-induced expression of VEGF mRNA and that the nuclear export of HuR is a rate-limiting step in this process. HuR appears to transiently stabilize VEGF transcripts after ACTH stimulation of adrenocortical cells, and Tis11b appears to subsequently trigger their degradation.

scholarly journals Lipopolysaccharide Enhances the Production of Vascular Endothelial Growth Factor by Human Pulp Cells in Culture

1999 ◽  
Vol 67 (4) ◽  
pp. 1633-1639 ◽  
Author(s):  
K. Matsushita ◽  
R. Motani ◽  
T. Sakuta ◽  
S. Nagaoka ◽  
T. Matsuyama ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Protein Synthesis ◽  
Growth Factor ◽  
Mrna Expression ◽  
Skin Fibroblasts ◽  
Vascular Endothelial ◽  
Vegf Mrna ◽  
Pulp Cells ◽  
Endothelial Growth Factor ◽  
Vegf Mrna Expression

ABSTRACT We investigated whether vascular endothelial growth factor (VEGF) production by human pulp cells (HPC) is regulated by lipopolysaccharide (LPS) in relation to the pathogenesis of pulpitis. Although HPC incubated with medium alone only marginally expressed VEGF mRNA and produced a low level of VEGF as detected by enzyme-linked immunosorbent assay, the VEGF mRNA expression and VEGF production were markedly enhanced upon stimulation with LPS from Escherichia coli. Prevotella intermedia LPS, phorbol 12-myristate 13-acetate, and interleukin-6 also induced VEGF mRNA expression in HPC. A simian virus 40-infected HPC line also exhibited increased VEGF mRNA expression in response to E. coli LPS, but lung and skin fibroblasts did not. Fetal bovine serum (FBS) increased the sensitivity of HPC to LPS in a dose-dependent manner. HPC did not express membrane CD14 on their surfaces. However, the anti-CD14 monoclonal antibody MY4 inhibited VEGF induction upon stimulation with LPS in HPC cultures in the presence of 10% FBS but not in the absence of FBS. LPS augmented the VEGF production in HPC cultures in the presence of recombinant human soluble CD14 (sCD14). To clarify the mechanisms of VEGF induction by LPS, we examined the possible activation of the transcription factor AP-1 in HPC stimulated with LPS, by a gel mobility shift assay. AP-1 activation in HPC was clearly observed, whereas that in skin fibroblasts was not. The AP-1 inhibitor curcumin strongly inhibited LPS-induced VEGF production in HPC cultures. In addition, a protein synthesis inhibitor, cycloheximide, inhibited VEGF mRNA accumulation in response to LPS. These results suggest that the enhanced production of VEGF in HPC induced by LPS takes place via an sCD14-dependent pathway which requires new protein synthesis and is mediated in part through AP-1 activation.

scholarly journals Stimulatory effects of fasting on vascular endothelial growth factor (VEGF) production by growing pig ovarian follicles

Reproduction ◽  
2003 ◽  
pp. 647-652 ◽  
Author(s):  
G Galeati ◽  
M Spinaci ◽  
N Govoni ◽  
A Zannoni ◽  
P Fantinati ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Follicular Fluid ◽  
Ovarian Follicles ◽  
Vascular Endothelial ◽  
Vegf Mrna ◽  
Vessel Permeability ◽  
Growing Pig ◽  
Endothelial Growth Factor ◽  
Vegf Mrna Expression

The aim of this study was to investigate the effect of fasting on both vascular endothelial growth factor (VEGF) production and VEGF mRNA expression in growing ovarian follicles (>5 mm in diameter) from gilts at 48 h after equine chorionic gonadotrophin (eCG) treatment. The concentrations of VEGF and albumin were measured in the follicular fluid of single follicles, and VEGF mRNA was determined in the follicle wall. Fasting resulted in a significant increase in VEGF concentrations in follicular fluid (20.64+/-0.72 versus 10.79+/-0.86 ng ml(-1), P<0.001), but it did not affect the total amount of VEGF mRNA in the follicle wall compared with that of fed animals. However, VEGF mRNA in the theca and granulosa compartments increased and decreased, respectively, compared with that of fed animals. The concentrations of albumin measured in follicular fluid as an index of vessel permeability were higher in fasted than in animals fed normally, most likely as a result of the increased VEGF production. Follicular steroidogenesis was impaired in fasted animals. Progesterone was the most abundant steroid in the follicular fluid and oestradiol was present in lower concentrations, thus indicating an alteration in the steroidogenic enzymatic cascade. In conclusion, fasting induces an increase in both VEGF production and vessel permeability. Such a reaction is unable under severe food deprivation to preserve follicle function, but may represent a mechanism that regulates blood vessel extension and distribution in relation to tissue requirements and availability of systemic nutrient.

A reassessment of vascular endothelial growth factor in central nervous system pathology

2005 ◽  
Vol 103 (5) ◽  
pp. 853-868 ◽  
Author(s):  
Marsha J. Merrill ◽  
Edward H. Oldfield
Keyword(s):  
Central Nervous System ◽  
Vascular Endothelial Growth Factor ◽  
Nervous System ◽  
Growth Factor ◽  
Causative Factor ◽  
Vascular Endothelial ◽  
Cns Disorders ◽  
Content Type ◽  
Endothelial Growth Factor ◽  
Fine Print

✓ Overexpression of vascular endothelial growth factor (VEGF) is associated with several central nervous system (CNS) diseases and abnormalities, and is often postulated as a causative factor and promising therapeutic target in these settings. The authors' goal was to reassess the contribution of VEGF to the biology and pathology of the CNS. The authors review the literature relating to the following aspects of VEGF: 1) the biology of VEGF in normal brain; 2) the involvement of VEGF in CNS disorders other than tumors (traumatic and ischemic injuries, arteriovenous malformations, inflammation); and 3) the role of VEGF in brain tumor biology (gliomas and the associated vasogenic edema, and hemangioblastomas). The authors conclude the following: first, that VEGF overexpression contributes to the phenotype associated with many CNS disorders, but VEGF is a reactive rather than a causative factor in many cases; and second, that use of VEGF as a therapeutic agent or target is complicated by the effects of VEGF not only on the cerebral vasculature, but also on astrocytes, neurons, and inflammatory cells. In many cases, therapeutic interventions targeting the VEGF/VEGF receptor axis are likely to be ineffective or even detrimental. Clinical manipulation of VEGF levels in the CNS must be approached with caution.

scholarly journals Statins Augment Vascular Endothelial Growth Factor Expression in Osteoblastic Cells via Inhibition of Protein Prenylation

Endocrinology ◽  
2003 ◽  
Vol 144 (2) ◽  
pp. 681-692 ◽  
Author(s):  
Toyonobu Maeda ◽  
Tetsuya Kawane ◽  
Noboru Horiuchi
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Mrna Expression ◽  
Osteoblastic Cells ◽  
Vascular Endothelial ◽  
Protein Prenylation ◽  
Vegf Expression ◽  
Vegf Mrna ◽  
Endothelial Growth Factor ◽  
Vegf Mrna Expression

Statins such as simvastatin are 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors that inhibit cholesterol synthesis. We presently investigated statin effects on vascular endothelial growth factor (VEGF) expression in osteoblastic cells. Hydrophobic statins including simvastatin, atorvastatin, and cerivastatin–but not a hydrophilic statin, pravastatin–markedly increased VEGF mRNA abundance in nontransformed osteoblastic cells (MC3T3-E1). Simvastatin (10−6m) time-dependently augmented VEGF mRNA expression in MC3T3-E1 cells, mouse stromal cells (ST2), and rat osteosarcoma cells (UMR-106). According to heterogeneous nuclear RNA and Northern analyses, 10−6m simvastatin stimulated gene expression for VEGF in MC3T3-E1 cells without altering mRNA stability. Transcriptional activation of a VEGF promoter-luciferase construct (−1128 to +827), significantly increased by simvastatin administration. As demonstrated by gel mobility shift assay, simvastatin markedly enhanced the binding of hypoxia-responsive element-protein complexes. These results indicate that the stimulation of the VEGF gene by simvastatin in MC3T3-E1 cells is transcriptional in nature. VEGF secretion into medium was increased in MC3T3-E1 by 10−6m simvastatin. Pretreating MC3T3-E1 cells with mevalonate or geranylgeranyl pyrophosphate, a mevalonate metabolite, abolished simvastatin-induced VEGF mRNA expression; manumycin A, a protein prenylation inhibitor, mimicked statin effects on VEGF expression. The effect of simvastatin was blocked by pretreatment with wortmannin and LY294002, specific phosphatidylinositide-3 kinase inhibitors. Simvastatin enhanced mineralized nodule formation in culture, whereas coincubation with mevalonate, geranylgeranyl pyrophosphate, LY294002, or VEGF receptor 2 inhibitor (SU1498) abrogated statin-induced mineralization. Thus, statins stimulate VEGF expression in osteoblasts via reduced protein prenylation and the phosphatidylinositide-3 kinase pathway, promoting osteoblastic differentiation.

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