Vascular Endothelial Growth Factor Is the Major Angiogenic Factor in Omentum: Mechanism of the Omentum-Mediated Angiogenesis

Vascular endothelial growth factor (VEGF) is a well-known angiogenic factor that plays a critical role in various physiological and pathological processes. VEGF also contributes to the process of embryo implantation by enhancing embryo development, improving endometrial receptivity, and facilitating the interactions between the developing embryo and the endometrium. There is a correlation between the alteration of VEGF expression and reproductive failure, including recurrent implantation failure (RIF) and recurrent miscarriage (RM). In order to clarify the role of VEGF in embryo implantation, we reviewed recent literature concerning the expression and function of VEGF in the reproductive system around the time of embryo implantation and we provide a summary of the findings reported so far. We also explored the effects and the possible underlying mechanisms of action of VEGF in embryo implantation.

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Effect of directly acting anti-viral agents on immunological imprints in chronic HCV-4a patients: interleukin-10 and vascular endothelial growth factor genes expression level

Egyptian Liver Journal ◽

10.1186/s43066-021-00108-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Iman S. Naga ◽

Amel Abdel Fattah Kamel ◽

Said Ahmed Ooda ◽

Hadeer Muhammad Fath Elbab ◽

Rania Mohamed El-Sharkawy

Keyword(s):

Gene Expression ◽

Vascular Endothelial Growth Factor ◽

Hepatitis C Virus ◽

Hepatitis C ◽

Growth Factor ◽

Angiogenic Factor ◽

Vascular Endothelial ◽

Wide Range ◽

Chronic Hcv ◽

Endothelial Growth Factor

Abstract Background Hepatitis C virus infection is a global health challenge with Egypt being one of the highly affected countries. IL-10 has been suggested as a suitable marker to assess necroinflammation and to monitor the progression of liver damage. Vascular endothelial growth factor (VEGF) is a potent angiogenic factor playing a central role in many physiological as well as pathological processes. Several factors can be predictive of the response to treatment and achievement of SVR; some of which are host-related, and others are virus-related. The gene expression of IL-10 and VEGF have multiple effects for treatment response. The aim of the present work was to study the effect of treatment with directly acting agents (DAA) on the expression of VEGF and IL-10 genes in chronic hepatitis C virus-infected Egyptian genotype-4a patients. Twenty-five HCV subjects where evaluated for IL-10 and VEGF gene expression before and after treatment with DAA. Results IL-10 expression was downregulated in 92% of the cases. VEGF expression was heterogeneous showing spreading of values along a wide range with 64% of the cases being downregulated. Conclusion DAAs do not completely reverse the immunological imprints established upon chronic HCV infection.

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P0590ADVERSE RENAL OUTCOME FOLLOWING ADMINISTRATION OF INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR INHIBITORS IN A SINGLE TERTIARY CENTRE IN MALAYSIA

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p0590 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Maisarah Jalalonmuhali ◽

Tengku Ain Fathlun Tengku Kamalden ◽

Nurul 'Ain Sham Ismail ◽

See Yen Yong ◽

Wei Ting Teo ◽

...

Keyword(s):

Blood Pressure ◽

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Serum Creatinine ◽

Post Treatment ◽

Angiogenic Factor ◽

Renal Outcome ◽

Vascular Endothelial ◽

Anti Vegf ◽

Endothelial Growth Factor

Abstract Background and Aims Intravenous (IV) anti-vascular endothelial growth factor(VEGF) is a potent anti-angiogenic factor for the treatment of solid tumours. While, intravitreal anti-VEGF injection is used in the treatment for macular and retinal diseases. The effects of IV anti-VEGF agents are well documented to cause hypertension, renal impairment and proteinuria. However only few reports showed the significance of intravitreal anti-VEGF injection causing minimal change disease (MCD) and acute kidney injury (AKI). Hence, this study is to determine the outcome of renal function following intravitreal anti-VEGF injection. Method This is a prospective, cross sectional study recruiting patients from ophthalmology day-care operation theatre that were scheduled for intravitreal anti-VEGF injection in University Malaya Medical Centre (UMMC). On the day of the injection of anti-VEGF, patients’ demographic data (age, gender, medical background, medications), blood pressure, height, weight and investigations for serum creatinine and urine protein creatinine ratio (PCR) were collected. Following these, they will receive the intravitreal anti-VEGF as per schedule. All these patients were given a follow-up within 72hours to reassess blood pressure, serum creatinine and urine PCR. Results A total of 90 patients were recruited. However, 15 patients were subsequently excluded as there was no repeated serum creatinine at 72-hours post treatment. Their mean age was 67.25 ± 10.41. Among all, 3 patients had significance increased in serum creatinine (4%) with significance changed of urine PCR post treatment. Table 1 showed baseline parameters prior to treatment and table 2 was post treatment parameters. Higher serum creatinine and proteinuria pre intravitreal anti-VEGF were identified to have higher OR of 1.018 (95% CI 1.001-1.035) (p=0.043) and OR 1.004 (1.000-1.007) (p=0.025) respectively among those who developed AKI. In assessing the association between higher pre-treatment creatinine and proteinuria (independent variable) and development of AKI (dependent variable) estimated by logistic regression with no AKI as a reference group we found that there were no significance. Conclusion Following intravitreal anti-VEGF administration, there were no significant changes in blood pressure. However, 4% from our cohort had AKI and worsening proteinuria at 72 hours post treatment. These patients had higher serum creatinine and proteinuria prior to treatment. However, our study is underpowered to establish the relationship between intravitreal anti-VEGF and development of AKI. Further study with larger sample size and longer-term outcome is needed.

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Vascular Endothelial Growth Factor (VEGF) Serum Levels during Cancer Immunotherapy with IL-2: Preliminary Considerations

The International Journal of Biological Markers ◽

10.1177/172460089801300206 ◽

1998 ◽

Vol 13 (2) ◽

pp. 98-101 ◽

Cited By ~ 5

Author(s):

P. Lissoni ◽

L. Fumagalli ◽

L. Giani ◽

F. Rovelli ◽

G Confalonieri ◽

...

Keyword(s):

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Cancer Immunotherapy ◽

Cancer Patients ◽

Cell Cancer ◽

Free Fraction ◽

Serum Levels ◽

Angiogenic Factor ◽

Vascular Endothelial ◽

Endothelial Growth Factor

Neoangiogenesis has been proven to play a fundamental role in promoting cancer spread, and vascular endothelial growth factor (VEGF) is known to represent one of the most important angiogenic factors. The present study was planned to investigate changes in VEGF secretion in cancer patients undergoing immunotherapy with IL-2, with the aim of establishing whether VEGF variations play a role in mediating the IL-2-induced control of neoplastic diseases. The study involved 14 metastatic renal cell cancer patients treated with IL-2 immunotherapy (6 million IU/day subcutaneously for 6 days/week for 4 weeks). The clinical response consisted of partial response (PR) in 3, stable disease (SD) in 6 and progressive disease (PD) in the remaining 5 patients. VEGF serum levels were measured by an enzyme immunoassay designed to determine both bound and unbound VEGF. No significant changes in VEGF mean levels occurred during IL-2 therapy. Moreover, neither in patients with PR or SD nor in those with PD did the mean serum levels of VEGF change significantly in response to IL-2. This preliminary study seems to exclude that changes in the angiogenic factor VEGF may play a role in mediating the therapeutic efficacy of IL-2 cancer immunotherapy. However, since the method of measurement used in our study was designed to detect the total amount of VEGF, it cannot be excluded that changes in the free fraction of the molecule may occur during IL-2 cancer immunotherapy.

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Expression of Vascular Endothelial Growth Factor at the Human Gastric Ulcer Margin and in Cultured Gastric Fibroblasts: A New Angiogenic Factor for Gastric Ulcer Healing

Biochemical and Biophysical Research Communications ◽

10.1006/bbrc.1997.5974 ◽

1997 ◽

Vol 234 (2) ◽

pp. 493-498 ◽

Cited By ~ 46

Author(s):

Morio Takahashi ◽

Takao Kawabe ◽

Keiji Ogura ◽

Shin Maeda ◽

Yasuyo Mikami ◽

...

Keyword(s):

Vascular Endothelial Growth Factor ◽

Gastric Ulcer ◽

Growth Factor ◽

Ulcer Healing ◽

Angiogenic Factor ◽

Vascular Endothelial ◽

Gastric Ulcer Healing ◽

Ulcer Margin ◽

Endothelial Growth Factor

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Bone Morphogenetic Proteins Stimulate Angiogenesis through Osteoblast-Derived Vascular Endothelial Growth Factor A

Endocrinology ◽

10.1210/endo.143.4.8719 ◽

2002 ◽

Vol 143 (4) ◽

pp. 1545-1553 ◽

Cited By ~ 328

Author(s):

Martine M. L. Deckers ◽

Rutger L. van Bezooijen ◽

Geertje van der Horst ◽

Jakomijn Hoogendam ◽

Chris van der Bent ◽

...

Keyword(s):

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Bone Formation ◽

Bone Morphogenetic Proteins ◽

Cross Talk ◽

Osteoblast Differentiation ◽

Angiogenic Factor ◽

Vascular Endothelial ◽

Endothelial Growth Factor

Abstract During bone formation and fracture healing there is a cross-talk between endothelial cells and osteoblasts. We previously showed that vascular endothelial growth factor A (VEGF-A) might be an important factor in this cross-talk, as osteoblast-like cells produce this angiogenic factor in a differentiation-dependent manner. Moreover, exogenously added VEGF-A enhances osteoblast differentiation. In the present study we investigated, given the coupling between angiogenesis and bone formation, whether bone morphogenetic proteins (BMPs) stimulate osteoblastogenesis and angiogenesis through the production of VEGF-A. For this we used the murine preosteoblast-like cell line KS483, which forms mineralized nodules in vitro, and an angiogenesis assay comprising 17-d-old fetal mouse bone explants that have the ability to form tube-like structures in vitro. Treatment of KS483 cells with BMP-2, -4, and -6 enhanced nodule formation, osteocalcin mRNA expression, and subsequent mineralization after 18 d of culture. This was accompanied by a dose-dependent increase in VEGF-A protein levels throughout the culture period. BMP-induced osteoblast differentiation, however, was independent of VEGF-A, as blocking VEGF-A activity by a VEGF-A antibody or a VEGF receptor 2 tyrosine kinase inhibitor did not affect BMP-induced mineralization. To investigate whether BMPs stimulate angiogenesis through VEGF-A, BMPs were assayed for their angiogenic activity. Treatment of bone explants with BMPs enhanced angiogenesis. This was inhibited by soluble BMP receptor 1A or noggin. In the presence of a VEGF-A antibody, both unstimulated and BMP-stimulated angiogenesis were arrested. Conditioned media of KS483 cells treated with BMPs also induced a strong angiogenic response, which was blocked by antimouse VEGF-A but not by noggin. These effects were specific for BMPs, as TGFβ inhibited osteoblast differentiation and angiogenesis while stimulating VEGF-A production. These findings indicate that BMPs stimulate angiogenesis through the production of VEGF-A by osteoblasts. In conclusion, VEGF-A produced by osteoblasts in response to BMPs is not involved in osteoblast differentiation, but couples angiogenesis to bone formation.

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Adenovirus-mediated expression of vascular endothelial growth factor-a potentiates bone morphogenetic protein9-induced osteogenic differentiation and bone formation

Biological Chemistry ◽

10.1515/hsz-2015-0296 ◽

2016 ◽

Vol 397 (8) ◽

pp. 765-775 ◽

Cited By ~ 2

Author(s):

Chang-jun Pi ◽

Kai-lu Liang ◽

Zhen-yong Ke ◽

Fu Chen ◽

Yun Cheng ◽

...

Keyword(s):

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Bone Formation ◽

Osteogenic Differentiation ◽

Bone Repair ◽

Osteoporotic Fractures ◽

Angiogenic Factor ◽

Vascular Endothelial ◽

Akt Inhibitor ◽

Endothelial Growth Factor

Abstract Mesenchymal stem cells (MSCs) are suitable seed cells for bone tissue engineering because they can self-renew and undergo differentiation into osteogenic, adipogenic, chondrogenic, or myogenic lineages. Vascular endothelial growth factor-a (VEGF-a), an angiogenic factor, is also involved in osteogenesis and bone repair. However, the effects of VEGF-a on osteogenic MSCs differentiation remain unknown. It was previously reported that bone morphogenetic protein9 (BMP9) is one of the most important osteogenic BMPs. Here, we investigated the effects of VEGF-a on BMP9-induced osteogenesis with mouse embryo fibroblasts (MEFs). We found that endogenous VEGF-a expression was undetectable in MSCs. Adenovirus-mediated expression of VEGF-a in MEFs potentiated BMP9-induced early and late osteogenic markers, including alkaline phosphatase (ALP), osteocalcin (OCN), and osteopontin (OPN). In stem cell implantation assays, VEGF-a augmented BMP9-induced ectopic bone formation. VEGF-a in combination with BMP9 effectively increased the bone volume and osteogenic activity. However, the synergistic effect was efficiently abolished by the phosphoinositide 3-kinase (PI3K)/AKT inhibitor LY294002. These results demonstrated that BMP9 may crosstalk with VEGF-a through the PI3K/AKT signaling pathway to induce osteogenic differentiation in MEFs. Thus, our findings demonstrate the effects of VEGF-a on BMP9-induced bone formation and provide a new potential strategy for treating nonunion fractures, large segmental bony defects, and/or osteoporotic fractures.

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Association of Vascular Endothelial Growth Factor Gene Polymorphisms With Susceptibility to Epithelial Ovarian Cancer

International Journal of Gynecological Cancer ◽

10.1111/igc.0b013e3181dbd32b ◽

2010 ◽

Vol 20 (5) ◽

pp. 717-723 ◽

Cited By ~ 10

Author(s):

Yan Li ◽

Yan Wang ◽

Shan Kang ◽

Na Wang ◽

Rong-Miao Zhou ◽

...

Keyword(s):

Ovarian Cancer ◽

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Confidence Interval ◽

Epithelial Ovarian Cancer ◽

Odds Ratio ◽

Gene Polymorphisms ◽

Angiogenic Factor ◽

Vascular Endothelial ◽

Endothelial Growth Factor

Background:Vascular endothelial growth factor (VEGF) is a major angiogenic factor involved in a number of pathological processes, including neovascularization, a crucial step in the development of solid malignancies. The aim of this study was to investigate the association of polymorphisms in the VEGF gene with susceptibility to epithelial ovarian cancer (EOC).Methods:This case-control study included 303 EOC patients and 303 healthy controls. Genotyping of the VEGF gene polymorphisms at −460C/T, −1154G/A, −2578C/A, and +936C/T were performed by polymerase chain reaction and restriction fragment length polymorphism analysis.Results:No significant difference was found in allele and genotype distributions of the −460C/T, +936C/T, and −2578C/A polymorphisms between patients and controls. However, the frequencies of −1154G/A genotype and allele were significantly different between the two groups (P = 0.037, P = 0.013). Compared with the G/A + A/A genotype, the G/G genotype could significantly increase the risk of developing EOC (odds ratio, 1.64; 95% confidence interval, 1.12-2.39). The haplotype analysis suggested that the −460T/−1154A/−2578C haplotype exhibited a decrease in the risk of developing EOC compared with the −460T/−1154G/−2578C haplotype (odds ratio, 0.644; 95% confidence interval, 0.415-0.999).Conclusions:The study suggested a possible association between the VEGF −1154G/A polymorphism with susceptibility to EOC, but there is no support for an association of the VEGF −460C/T, +936C/T, and −2578C/A polymorphisms with the risk for EOC.

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Stabilization of vascular endothelial growth factor mRNA by hypoxia and hypoglycemia and coregulation with other ischemia-induced genes.

Molecular and Cellular Biology ◽

10.1128/mcb.15.10.5363 ◽

1995 ◽

Vol 15 (10) ◽

pp. 5363-5368 ◽

Cited By ~ 315

Author(s):

I Stein ◽

M Neeman ◽

D Shweiki ◽

A Itin ◽

E Keshet

Keyword(s):

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Half Life ◽

Angiogenic Factor ◽

Dependent Manner ◽

Vascular Endothelial ◽

Vegf Mrna ◽

Glut 1 ◽

Induced Genes ◽

Endothelial Growth Factor

Expression of vascular endothelial growth factor (VEGF), an endothelial cell-specific mitogen and a potent angiogenic factor, is upregulated in response to a hypoxic or hypoglycemic stress. Here we show that the increase in steady-state levels of VEGF mRNA is partly due to transcriptional activation but mostly due to increase in mRNA stability. Both oxygen and glucose deficiencies result in extension of the VEGF mRNA half-life in a protein synthesis-dependent manner. Viewing VEGF as a stress-induced gene, we compared its mode of regulation with that of other stress-induced genes. Results showed that under nonstressed conditions, VEGF shares with the glucose transporter GLUT-1 a relatively short half-life (0.64 and 0.52 h, respectively), which is extended fourfold and more than eightfold, respectively, when cells are deprived of either oxygen or glucose. In contrast, the mRNAs of another hypoxia-inducible and hypoglycemia-inducible gene, grp78, as well as that of HSP70, were not stabilized by these metabolic insults. To show that VEGF and GLUT-1 are coinduced in differentially stressed microenvironments, multicell spheroids representing a clonal population of glioma cells in which each cell layer is differentially stressed were analyzed by in situ hybridization. Cellular microenvironments conducive to induction of VEGF and GLUT-1 were completely coincidental. These findings show that two different consequences of tissue ischemia, namely, hypoxia and glucose deprivation, induce VEGF and GLUT-1 expression by similar mechanisms. These proteins function, in turn, to satisfy the tissue needs through expanding its vasculature and improving its glucose utilization, respectively.

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