Rat brain VEGF expression in alveolar hypoxia: possible role in high-altitude cerebral edema

1998 ◽  
Vol 85 (1) ◽  
pp. 53-57 ◽  
Author(s):  
Fengping Xu ◽  
John W. Severinghaus
Keyword(s):  
High Altitude ◽  
Cerebral Edema ◽  
Northern Blot Analysis ◽  
Capillary Permeability ◽  
Vascular Endothelial ◽  
Vegf Expression ◽  
Vegf Mrna ◽  
High Altitude Cerebral Edema ◽  
Alveolar Hypoxia ◽  
Endothelial Growth Factor

The mechanism by which hypoxia causes high-altitude cerebral edema (HACE) is unknown. Tissue hypoxia triggers angiogenesis, initially by expressing vascular endothelial growth factor (VEGF), which has been shown to increase extracerebral capillary permeability. This study investigated brain VEGF expression in 32 rats exposed to progressively severe normobaric hypoxia (9–6% O2) for 0 (control), 3, 6, or 12 h or 1, 2, 3, or 6 days. O2concentration was adjusted intermittently to the limit of tolerance by activity and intake, but no attempt was made to detect HACE. Northern blot analysis demonstrated that two molecular bands of transcribed VEGF mRNA (∼3.9 and 4.7 kb) were upregulated in cortex and cerebellum after as little as 3 h of hypoxia, with a threefold increase peaking at 12–24 h. Western blot revealed that VEGF protein was increased after 12 h of hypoxia, reaching a maximum in ∼2 days. The expression of flt-1 mRNA was enhanced after 3 days of hypoxia. We conclude that VEGF production in hypoxia is consistent with the hypothesis that angiogenesis may be involved in HACE.

scholarly journals VEGF, VEGF165b and EG-VEGF expression is specifically related with hormone profile in pituitary adenomas

2019 ◽  
Vol 63 (1) ◽  
Author(s):  
Ana Silvia Corlan ◽  
Anca Maria Cîmpean ◽  
Eugen Melnic ◽  
Marius Raica ◽  
Simona Sarb
Keyword(s):  
Pituitary Adenomas ◽  
P Value ◽  
Endocrine Gland ◽  
Vascular Endothelial ◽  
Vegf Expression ◽  
Vegf Mrna ◽  
Folliculostellate Cells ◽  
Hormone Profile ◽  
Hormonal Milieu ◽  
Endothelial Growth Factor

Vascular endothelial growth factor (VEGF), its inhibitory splice variant, VEGF165b and Endocrine Gland derived VEGF (EG-VEGF) have a controversial role in pituitary gland. We aim to study VEGF, VEGF165b and EG-VEGF expression in pituitary adenomas. A significant correlation was found between growth hormone (GH) and VEGF secretion (P=0.024). For prolactinomas, VEGF and prolactin expression, had a P-value of 0.02 for Kendall coefficient and a P-value of 0.043 for the Spearman coefficient. VEGF-mRNA amplification was detected in both tumor cells and folliculostellate cells. VEGF165b was positive in 16.66% of pituitary adenomas. EG-VEGF was significantly correlated with prolactin (P=0.025) and luteinizing hormone (P=0.028). Our data strongly support VEGF, VEGF165b and EG-VEGF as important players of pituitary adenomas tumorigenesis. Particular hormonal milieu heterogeneity, special vascular network with an unusual reactivity to tumor growth correlated with variability of VEGF, VEGF165b and EG-VEGF secretion may stratify pituitary adenomas in several molecular groups with a direct impact on therapy and prognosis.

Transforming growth factor-β1 modulates the expression of vascular endothelial growth factor by osteoblasts

1999 ◽  
Vol 277 (4) ◽  
pp. C628-C637 ◽  
Author(s):  
Pierre B. Saadeh ◽  
Babak J. Mehrara ◽  
Douglas S. Steinbrech ◽  
Matthew E. Dudziak ◽  
Joshua A. Greenwald ◽  
...  
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Vascular Endothelial ◽  
Vegf Expression ◽  
Vegf Mrna ◽  
Endothelial Growth Factor ◽  
Dose Dependent ◽  
Tgf Β1 ◽  
Vegf Protein

Angiogenesis is essential to both normal and pathological bone physiology. Vascular endothelial growth factor (VEGF) has been implicated in angiogenesis, whereas transforming growth factor-β1 (TGF-β1) modulates bone differentiation, matrix formation, and cytokine expression. The purpose of this study was to investigate the relationship between TGF-β1 and VEGF expression in osteoblasts and osteoblast-like cells. Northern blot analysis revealed an early peak of VEGF mRNA (6-fold at 3 h) in fetal rat calvarial cells and MC3T3-E1 osteoblast-like cells after stimulation with TGF-β1 (2.5 ng/ml). The stability of VEGF mRNA in MC3T3-E1 cells was not increased after TGF-β1 treatment. Actinomycin D inhibited the TGF-β1-induced peak in VEGF mRNA, whereas cycloheximide did not. Blockade of TGF-β1 signal transduction via a dominant-negative receptor II adenovirus significantly decreased TGF-β1 induction of VEGF mRNA. Additionally, TGF-β1 induced a dose-dependent increase in VEGF protein expression by MC3T3-E1 cells ( P < 0.01). Dexamethasone similarly inhibited VEGF protein expression. Both TGF-β1 mRNA and VEGF mRNA were concurrently present in rat membranous bone, and both followed similar patterns of expression during rat mandibular fracture healing (mRNA and protein). In summary, TGF-β1-induced VEGF expression by osteoblasts and osteoblast-like cells is a dose-dependent event that may be intimately related to bone development and fracture healing.

scholarly journals Hypoxic Regulation of Vascular Endothelial Growth Factor mRNA Stability Requires the Cooperation of Multiple RNA Elements

1999 ◽  
Vol 10 (4) ◽  
pp. 907-919 ◽  
Author(s):  
J. A. Dibbens ◽  
D. L. Miller ◽  
A. Damert ◽  
W. Risau ◽  
M. A. Vadas ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Vascular Endothelial ◽  
Coding Region ◽  
Vegf Gene ◽  
Vegf Expression ◽  
Vegf Mrna ◽  
Rapid Degradation ◽  
Multiple Regions ◽  
Endothelial Growth Factor

Vascular endothelial growth factor (VEGF) is a key regulator of developmental, physiological, and tumor angiogenesis. Upregulation of VEGF expression by hypoxia appears to be a critical step in the neovascularization of solid cancers. The VEGF mRNA is intrinsically labile, but in response to hypoxia the mRNA is stabilized. We have systematically analyzed the regions in the VEGF mRNA that are responsible for its lability under normoxic conditions and for stabilization in response to hypoxia. We find that the VEGF mRNA not only contains destabilizing elements in its 3′ untranslated region (3′UTR), but also contains destabilizing elements in the 5′UTR and coding region. Each region can independently promote mRNA degradation, and together they act additively to effect rapid degradation under normoxic conditions. Stabilization of the mRNA in response to hypoxia is completely dependent on the cooperation of elements in each of the 5′UTR, coding region, and 3′UTR. Combinations of any of two of these three regions were completely ineffective in responding to hypoxia, whereas combining all three regions allowed recapitulation of the hypoxic stabilization seen with the endogenous VEGF mRNA. We conclude that multiple regions in the VEGF mRNA cooperate both to ensure the rapid degradation of the mRNA under normoxic conditions and to allow stabilization of the mRNA in response to hypoxia. Our findings highlight the complexity of VEGF gene expression and also reveal a mechanism of gene regulation that could become the target for strategies of therapeutic intervention.

scholarly journals Greater free plasma VEGF and lower soluble VEGF receptor-1 in acute mountain sickness

2005 ◽  
Vol 98 (5) ◽  
pp. 1626-1629 ◽  
Author(s):  
Martha C. Tissot van Patot ◽  
Guy Leadbetter ◽  
Linda E. Keyes ◽  
Jamie Bendrick-Peart ◽  
Virginia E. Beckey ◽  
...  
Keyword(s):  
High Altitude ◽  
Acute Mountain Sickness ◽  
Significant Rise ◽  
Vegf Receptor ◽  
Vascular Endothelial ◽  
High Altitude Cerebral Edema ◽  
Mountain Sickness ◽  
Low Altitude ◽  
Endothelial Growth Factor ◽  
Free Plasma

Vascular endothelial growth factor (VEGF) is a hypoxia-induced protein that produces vascular permeability, and limited evidence suggests a possible role for VEGF in the pathophysiology of acute mountain sickness (AMS) and/or high-altitude cerebral edema (HACE). Previous studies demonstrated that plasma VEGF alone does not correlate with AMS; however, soluble VEGF receptor (sFlt-1), not accounted for in previous studies, can bind VEGF in the circulation, reducing VEGF activity. In the present study, we hypothesized that free VEGF is greater and sFlt-1 less in subjects with AMS compared with well individuals at high altitude. Subjects were exposed to 4,300 m for 19–20 h (baseline 1,600 m). The incidence of AMS was determined by using a modified Lake Louise symptom score and the Environmental Symptoms Questionnaire for cerebral effects. Plasma was collected at low altitude and after 24 h at high altitude, or at time of illness, and then analyzed by ELISA for VEGF and for soluble VEGF receptor, sFlt-1. AMS subjects had lower sFlt-1 at both low and high altitude compared with well subjects and a significant rise in free plasma VEGF on ascent to altitude compared with well subjects. We conclude that increased free plasma VEGF on ascent to altitude is associated with AMS and may play a role in pathophysiology of AMS.

scholarly journals Effects of high glucose on vascular endothelial growth factor expression in vascular smooth muscle cells

1997 ◽  
Vol 273 (5) ◽  
pp. H2224-H2231 ◽  
Author(s):  
Rama Natarajan ◽  
Wei Bai ◽  
Linda Lanting ◽  
Noe Gonzales ◽  
Jerry Nadler
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Smooth Muscle ◽  
Growth Factor ◽  
Vascular Smooth Muscle Cells ◽  
Vascular Endothelial ◽  
Ang Ii ◽  
Vegf Expression ◽  
Vegf Mrna ◽  
Mrna And Protein Expression ◽  
Endothelial Growth Factor

Vascular endothelial growth factor (VEGF), in addition to its growth-promoting effects on endothelial cells, can also increase vascular permeability and monocyte migration. It has therefore been implicated in the pathogenic neovascularization associated with diabetic retinopathy and atherosclerosis. However, the factors regulating VEGF expression in the vascular wall are not fully understood. In this study, we examined the regulation of VEGF expression in vascular smooth muscle cells (VSMC) by hyperglycemia as well as by angiotensin II (ANG II). We also examined whether the 12-lipoxygenase (12-LO) product 12-hydroxyeicosatetraenoic acid (12-HETE) can alter VEGF expression, since 12-LO products of arachidonic acid have angiogenic properties, and ANG II as well as high glucose (HG, 25 mM) can increase 12-LO activity and expression in VSMC. Studies were carried out in human (HSMC) or porcine VSMC (PSMC), which were cultured for at least two passages under normal glucose (NG, 5.5 mM) or HG conditions. HG culture alone increased the expression of VEGF mRNA and protein in both HSMC and PSMC. Furthermore, ANG II treatment significantly induced VEGF mRNA and protein expression only in VSMC cultured in HG and not NG. In addition, 12-HETE significantly increased VEGF mRNA and protein expression in HSMC cultured in NG as well as in HG. Cells cultured in HG also secreted significantly greater amounts of VEGF into the culture medium. These results suggest that elevated VEGF production under HG conditions may play a role in the accelerated vascular disease observed in diabetes.

Expression of Vascular Endothelial Growth Factor in Human Monocyte/Macrophages Stimulated with Lipopolysaccharide

2001 ◽  
Vol 85 (01) ◽  
pp. 171-176 ◽  
Author(s):  
Hiroyuki Itaya ◽  
Hidemi Yoshida ◽  
Masayuki Koyama ◽  
Sohei Suzuki ◽  
Kei Satoh ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Endothelial Cells ◽  
Growth Factor ◽  
Map Kinase ◽  
Human Monocyte ◽  
P38 Map Kinase ◽  
Vascular Endothelial ◽  
Vegf Expression ◽  
Vegf Mrna ◽  
Endothelial Growth Factor

SummaryVascular endothelial growth factor (VEGF) is a mitogen for endothelial cells. We have studied the production of VEGF by human macrophages in response to lipopolysaccharide (LPS). Macrophages stimulated with LPS expressed VEGF mRNA and protein in concentration- and time-dependent manners. The LPS-induced expression of VEGF was inhibited by cycloheximide pretreatment, which suggested that synthesis of certain factor(s) is required for the LPS activity. The induction of VEGF was also suppressed by SB203580, an inhibitor of p38 mitogen-activated protein (MAP) kinase. These results suggest that the LPS-induced VEGF expression depends on the p38-mediated expression of c-Jun, which constitutes the AP-1 complex and binds to the AP-1 site in the VEGF promoter. Pretreatment of the cells with dexamethasone did not affect the LPS-induced upregulation of VEGF mRNA but strongly inhibited VEGF protein production, and the involvement of posttranscriptional regulation on VEGF expression by dexamethasone was suggested. The conditioned medium of LPS-stimulated macrophages enhanced the growth of cultured endothelial cells and it was inhibited by an antibody against VEGF. We conclude that macrophages produce VEGF in response to the stimulation with LPS, which may be partly mediated by the p38 MAP kinase pathway.

scholarly journals The Effect of HRE-Regulated VEGF Expression and Transfection on Neural Stem Cells in Rats

2020 ◽  
Vol 8 ◽  
Author(s):  
Bo Dou ◽  
Xiangrong Zheng ◽  
Danfeng Tan ◽  
Xixi Yin
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Target Cells ◽  
Vascular Endothelial ◽  
Rt Pcr ◽  
Vegf Gene ◽  
Vegf Expression ◽  
Vegf Mrna ◽  
Endothelial Growth Factor ◽  
Vegf Protein

In this study, we analyzed neural stem cells transfected with the HRE-VEGF gene in groups experiencing different periods of hypoxia. The results of RT-PCR showed that the expression of vascular endothelial growth factor (VEGF) mRNA gradually increased with the prolonged period of hypoxia (p &lt; 0.05). The results from the western-blot test showed that expression of the VEGF protein increased with as the period of hypoxia increased (p &lt; 0.05). The results of MTT combined with Elisa reagent showed that with the prolonged period of hypoxia, the secretion of VEGF protein increased, and that the proliferation of target cells and neural stem cells was better promoted (p &lt; 0.05). These results imply that HRE can safely and effectively regulate VEGF expression. By controlling the period of hypoxia, we can increase the expression level, and limit it in more safe values to avoid the possibility of cancer caused by the over-enhancement of proliferation of target cells due to the overexpression of the VEGF protein.

scholarly journals Retinoic Acid Pathway Regulation of Vascular Endothelial Growth Factor in Ovine Amnion

2018 ◽  
Vol 26 (10) ◽  
pp. 1351-1359 ◽  
Author(s):  
Cecilia Y. Cheung ◽  
Debra F. Anderson ◽  
Marion Rouzaire ◽  
Loïc Blanchon ◽  
Vincent Sapin ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Retinoic Acid ◽  
Growth Factor ◽  
Mrna Levels ◽  
Vascular Endothelial ◽  
Gene Promoters ◽  
Vegf Expression ◽  
Vegf Mrna ◽  
Pregnant Sheep ◽  
Endothelial Growth Factor

Vascular endothelial growth factor (VEGF) has been proposed as an important regulator of amniotic fluid absorption across the amnion into the fetal vasculature on the surface of the placenta. However, the activators of VEGF expression and action in the amnion have not been identified. Using the pregnant sheep model, we aimed to investigate the presence of the retinoic acid (RA) pathway in ovine amnion and to determine its effect on VEGF expression. Further, we explored relationships between RA receptors and VEGF and tested the hypothesis that RA modulates intramembranous absorption (IMA) through induction of amnion VEGF in sheep fetuses subjected to altered IMA rates. Our study showed that RA receptor isoforms were expressed in sheep amnion, and RA response elements (RAREs) were identified in ovine RARβ and VEGF gene promoters. In ovine amnion cells, RA treatment upregulated RARβ messenger RNA (mRNA) and increased VEGF transcript levels. In sheep fetuses, increases in IMA rate was associated with elevated VEGF mRNA levels in the amnion but not in the chorion. Further, RARβ mRNA was positively correlated with VEGF mRNA levels in the amnion and not chorion. We conclude that an RA pathway is present in ovine fetal membranes and that RA is capable of inducing VEGF. The finding of a positive relationship between amnion VEGF and RARβ during altered IMA rate suggests that the retinoid pathway may play a role through VEGF in regulating intramembranous transport across the amnion.

scholarly journals Expression and localization of vascular endothelial growth factor and its receptors in pig corpora lutea during the oestrous cycle

Reproduction ◽  
2003 ◽  
pp. 393-405 ◽  
Author(s):  
U Boonyaprakob ◽  
JE Gadsby ◽  
V Hedgpeth ◽  
P Routh ◽  
GW Almond
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Northern Blot ◽  
Luteal Phase ◽  
Northern Blot Analysis ◽  
Corpora Lutea ◽  
Vegf Receptor ◽  
Vascular Endothelial ◽  
Vegf Mrna ◽  
Endothelial Growth Factor

Expression and localization of mRNAs for vascular endothelial growth factor (VEGF), VEGF receptor 1 (Flt) and VEGF receptor 2 (KDR) (VEGFR-1 and VEGFR-2, respectively) were investigated in pig corpora lutea. Northern blot analysis of total RNA indicated hybridization of pig VEGF, VEGFR-1 and VEGFR-2 cDNA probes to mRNA transcripts of approximately 3.9, 7.0 and 5.0 kb, respectively. The expression of mRNAs for VEGF and its receptors during the luteal phase (days 4, 7, 10, 13 and 15 after the onset of oestrus) were assessed by northern blot analysis, and hybridization signals were normalized to expression of pig 18S rRNA. Relative hybridization signals of expression of VEGF mRNA appeared to be constant; however, expression of VEGFR-1 mRNA was low on day 4, increased on day 7, and was higher on days 10, 13 and 15 (P<0.05, compared with day 4). In contrast, no changes in expression of mRNA for VEGFR-2 were evident on days 4-13, but a decrease was detected (P<0.05) at day 15. In situ hybridization revealed that VEGF mRNA was localized predominantly in large luteal cells, whereas both VEGFR-1 and VEGFR-2 were localized to small cells. These data indicate that the VEGF system may be involved in the regulation of luteal vasculature throughout the lifespan of the corpus luteum. Although the expression of VEGF mRNA was unchanged during the luteal phase, variations in the expression of VEGFR-1 and VEGFR-2 mRNAs indicate that differential regulation of expression of the VEGF receptors may play a role in the control of VEGF-mediated vascular growth at different phases of development and maturation of the pig corpus luteum.

scholarly journals Tristetraprolin Inhibits Ras-dependent Tumor Vascularization by Inducing Vascular Endothelial Growth Factor mRNA Degradation

2007 ◽  
Vol 18 (11) ◽  
pp. 4648-4658 ◽  
Author(s):  
Khadija Essafi-Benkhadir ◽  
Cercina Onesto ◽  
Emmanuelle Stebe ◽  
Christoph Moroni ◽  
Gilles Pagès
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Antitumor Agent ◽  
Mrna Degradation ◽  
Vascular Endothelial ◽  
Vegf Expression ◽  
Vegf Mrna ◽  
Angiogenic Potential ◽  
Angiogenic Switch ◽  
Endothelial Growth Factor

Vascular endothelial growth factor (VEGF) is one of the most important regulators of physiological and pathological angiogenesis. Constitutive activation of the extracellular signal-regulated kinase (ERK) pathway and overexpression of VEGF are common denominators of tumors from different origins. We have established a new link between these two fundamental observations converging on VEGF mRNA stability. In this complex phenomenon, tristetraprolin (TTP), an adenylate and uridylate-rich element-associated protein that binds to VEGF mRNA 3′-untranslated region, plays a key role by inducing VEGF mRNA degradation, thus maintaining basal VEGF mRNA amounts in normal cells. ERKs activation results in the accumulation of TTP mRNA. However, ERKs reduce the VEGF mRNA-destabilizing effect of TTP, leading to an increase in VEGF expression that favors the angiogenic switch. Moreover, TTP decreases RasVal12-dependent VEGF expression and development of vascularized tumors in nude mice. As a consequence, TTP might represent a novel antiangiogenic and antitumor agent acting through its destabilizing activity on VEGF mRNA. Determination of TTP and ERKs status would provide useful information for the evaluation of the angiogenic potential in human tumors.

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