scholarly journals Vascular Endothelial Growth Factor Induces Abnormal Microvasculature in the Endoglin Heterozygous Mouse Brain

2004 ◽  
Vol 24 (2) ◽  
pp. 237-244 ◽  
Author(s):  
Bin Xu ◽  
Yong Qin Wu ◽  
Madeleine Huey ◽  
Helen M. Arthur ◽  
Douglas A. Marchuk ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Mouse Brain ◽  
Disease Model ◽  
Cell Types ◽  
Saline Group ◽  
Vegf Receptor ◽  
Vascular Endothelial ◽  
Loss Of Function ◽  
Endothelial Growth Factor

Hereditary hemorrhagic telangiectasia (HHT), associated with brain arteriovenous malformations, is caused by a loss of function mutation in either the endoglin (HHT1) or activin receptor-like kinase 1 gene (ALK-1, HHT2). Endoglin heterozygous ( Eng+/−)mice have been proposed as a disease model. To better understand the role of endoglin in vascular malformation development, we examined the effect of vascular endothelial growth factor (VEGF) hyperstimulation on microvessels in adult endoglin heterozygous ( Eng+/−) mice using an adenoviral vector to deliver recombinant human VEGF165 cDNA (Ad hVEGF) into basal ganglia. VEGF expression was increased in Ad hVEGF mice compared with the Ad lacZ and saline group ( P < 0.05) and localized to multiple cell types (neurons, astrocytes, endothelial cells, and smooth muscle cells) by double-labeled immunostaining. VEGF overexpression increased microvessel count for up to 4 weeks in both the Eng+/+ and Eng+/+ groups ( Eng+/+ 185 ± 14 vs. Eng+/− 201 ± 10 microvessels/mm2). Confocal microscopic examination revealed grossly abnormal microvessels in eight of nine Eng+/− mouse brains compared with zero of nine in Eng+/+ mice ( P < 0.05). Abnormal microvessels featured enlargement, clustering, twist, or spirals. VEGF receptor Flk-1 and TGF-β receptor 1 (TβR1) expression were reduced in the Eng+/− mouse brain compared with control. Excessive VEGF stimulation may play a pivotal role in the initiation and development of brain vessel malformations in states of relative endoglin insufficiency in adulthood. These observations are relevant to our general understanding of the maintenance of vascular integrity.

Signal transduction by vascular endothelial growth factor receptors

2003 ◽  
Vol 31 (1) ◽  
pp. 20-24 ◽  
Author(s):  
L. Claesson-Welsh
Keyword(s):  
Signal Transduction ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Cell Types ◽  
Vegf Receptor ◽  
Vascular Endothelial ◽  
Lymphatic Endothelial Cells ◽  
Vascular Permeability Factor ◽  
Wide Range ◽  
Endothelial Growth Factor

Vascular endothelial growth factor (VEGF)/vascular permeability factor is the prototype for a growing family of dimeric growth factors, which exert their effects on vascular and lymphatic endothelial cells, as well as on a wide range of other cell types. Gene targeting shows that most, if not all, of the factors and receptors in this family serve critical functions during vascular development or in adult physiological and pathological angiogenesis. Growing tumours produce VEGF, and many different strategies for inhibiting tumour growth by inhibiting VEGF production are being tested in clinical trials at present. This review focuses on the signal transduction properties of VEGF receptor-1 and VEGF receptor-2.

Vascular endothelial growth factor-induced secretion of fibronectin is ERK dependent

2004 ◽  
Vol 286 (3) ◽  
pp. L539-L545 ◽  
Author(s):  
Altaf S. Kazi ◽  
Shidan Lotfi ◽  
Elena A. Goncharova ◽  
Omar Tliba ◽  
Yassine Amrani ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Vascular Endothelial Growth Factor ◽  
Smooth Muscle ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Airway Remodeling ◽  
Vegf Receptor ◽  
Vascular Endothelial ◽  
Matrix Deposition ◽  
Endothelial Growth Factor

In severe asthma, cytokines and growth factors contribute to the proliferation of smooth muscle cells and blood vessels, and to the increased extracellular matrix deposition that constitutes the process of airway remodeling. Vascular endothelial growth factor (VEGF), which regulates vascular permeability and angiogenesis, also modulates the function of nonendothelial cell types. In this study, we demonstrate that VEGF induces fibronectin secretion by human airway smooth muscle (ASM) cells. In addition, stimulation of ASM with VEGF activates ERK, but not p38MAPK, and fibronectin secretion is ERK dependent. Both ERK activation and fibronectin secretion appear to be mediated through the VEGF receptor flt-1, as evidenced by the effects of the flt-1-specific ligand placenta growth factor. Finally, we demonstrate that ASM cells constitutively secrete VEGF, which is increased in response to PDGF, transforming growth factor-β, IL-1β, and PGE2. We conclude that ASM-derived VEGF, through modulation of the extracellular matrix, may play an important role in airway remodeling seen in asthma.

scholarly journals Correlation of vascular endothelial growth factor and vascular endothelial growth factor receptor-1 levels in serum and thyroid nodules with histopathological and radiological variables

2019 ◽  
Vol 11 (01) ◽  
pp. 051-057 ◽  
Author(s):  
Gurkan Haytaoglu ◽  
Fatih Kuzu ◽  
Dilek Arpaci ◽  
Ayfer Altas ◽  
Murat Can ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Thyroid Nodules ◽  
Statistical Significance ◽  
Growth Factor Receptor ◽  
Needle Aspiration ◽  
Vegf Receptor ◽  
Vascular Endothelial ◽  
Number Of Patients ◽  
Endothelial Growth Factor

Abstract BACKGROUND/AIM: Vascular endothelial growth factor (VEGF) is a major cytokine in angiogenesis and has a role on aggressivity of various tumors. The expression of VEGF has been shown to increase in differential thyroid cancer. The aim of the study was to evaluate serum and intranodular VEGF (nVEGF) and VEGF receptor-1 (VEGFR-1) levels in patients with thyroid nodules and their relevance to ultrasonographic and pathological results. MATERIALS AND METHODS: A total of eighty patients were included in the study. Thyroid fine-needle aspiration biopsies were performed, and the levels of serum and nVEGF and VEGFR-1 were measured. Any possible correlations between serum and nVEGF, VEGFR-1, and biochemical/radiological variables were investigated. RESULTS: There were no significant differences between serum VEGF (sVEGF), nVEGF, sVEGFR-1, nVEGFR-1 levels, number of nodules, size of nodules, and benign and malignant ultrasonographic features. sVEGF and nVEGF were higher in malignant or suspicious nodules than that in benign nodules, but did not reach statistical significance (P > 0.05). sVEGFR-1 and nVEGFR-1 levels were higher in hyperthyroid patients than that in euthyroid patients (P < 0.05 and P = 0.003, respectively). nVEGFR-1 level was higher in hypothyroid patients than that in euthyroid patients (P = 0.016). sVEGF level was found to be higher in hyperactive nodules than that in others. Both sVEGFR-1 (P = 0.008) and nVEGF levels (P = 0.01) significantly increased with increasing age. nVEGFR-1 decreased with increasing body mass index (BMI) (P = 0.004). CONCLUSIONS: Our study showed the relationships of sVEGF, nVEGF, sVEGFR-1, and nVEGFR-1 levels with age, gender, BMI, and hyperthyroidism. To determine the role of VEGF/VEGFR-1 in thyroid nodules, further studies are required with a large number of patients.

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