Disease relevance of VEGFA

• Moreover, elevated HES1 expression promotes progenitor cell proliferation and prevents overproduction of retinal ganglion cells owing to the loss of VEGF or sonic hedgehog (SHH), another signal that suppresses ganglion cell development [1].
• Hypoxia significantly increased both HIF-1alpha and VEGF protein production [2].
• Local application of 3-OH-GA alone or in combination with VEGF in chick chorioallantoic membrane induces abnormal vascular dilatation and hemorrhage in vivo [3].
• Dihydroartemisinin inhibits angiogenesis induced by multiple myeloma RPMI8226 cells under hypoxic conditions via downregulation of vascular endothelial growth factor expression and suppression of vascular endothelial growth factor secretion [4].
• Inhibition of vascular endothelial growth factor (VEGF)-165 and semaphorin 3A-mediated cellular invasion and tumor growth by the VEGF signaling inhibitor ZD4190 in human colon cancer cells and xenografts [5].

High impact information on VEGFA

• Vascular endothelial growth factor promotes endothelial cell differentiation, whereas mural cells are induced by platelet-derived growth factor-BB [6].
• Selective requirement for Src kinases during VEGF-induced angiogenesis and vascular permeability [7].
• Recent experiments show that chemotaxis, especially in response to members of the FGF, PDGF and VEGF families of growth factors, plays a key role in the guidance of mesoderm cells during gastrulation in chick, mouse and frog embryos [8].
• Signalling via vascular endothelial growth factor receptor-3 is sufficient for lymphangiogenesis in transgenic mice [9].
• In vitro treatments of human retinal pigment epithelial cells with CEP-dipeptide or CEP-HSA did not induce increased VEGF secretion [10].

Chemical compound and disease context of VEGFA

• BACKGROUND: Our previous study found that silymarin (SM) and its major pure component silibinin (SB) have anti-angiogenic effects via decreased vascular endothelium growth factor (VEGF) secretion of LoVo cells (colon cancer) [11].
• We recently showed that apigenin-inhibited hypoxia-inducible factor-1 (HIF-1) and vascular endothelial growth factor (VEGF) expression in human ovarian cancer cells under normoxic condition [12].
• METHODS: A chick embryo chorioallantoic membrane (CAM) model that bore human fibrosarcoma (HT1080) was used to determine whether the administration of physiologically relevant doses of ethanol could stimulate tumor growth, angiogenesis, metastasis, and vascular endothelial growth factor (VEGF) expression in tumors [13].
• 2,3,7,8-tetrachlorodibenzo-p-dioxin reduces myocardial hypoxia and vascular endothelial growth factor expression during chick embryo development [14].

Biological context of VEGFA

• Conversely, absorbing endogenous VEGF ligand or disrupting FLK1 activity attenuates cell proliferation and enhances retinal ganglion cell production [1].
• Gene expression of members of the VEGF and Angiopoietin families of angiogenic growth factors has been linked to haemorrhaging and oedema and we find widespread expression of VEGF-D, rigf and Ang2a in the talpid(3) limb [15].
• The in vivo cancer growth suppression was associated with a decreased microvessel density and VEGF abundance as well as an increased PARP cleavage and the TUNEL-positive apoptosis [16].
• Vascular endothelial growth factor D (VEGF-D) is a member of the VEGF/PDGF superfamily that has been implicated in angiogenesis and lymphangiogenesis [17].
• Vascular endothelial growth factor (VEGF) is a major regulator of endothelial cell proliferation, angiogenesis and vascular permeability, and its activities are mediated by two receptors, VEGFR-1 and VEGFR-2 [18].

Anatomical context of VEGFA

• VEGF activates divergent intracellular signaling components to regulate retinal progenitor cell proliferation and neuronal differentiation [1].
• Augmenting VEGF signals increases progenitor cell proliferation and decreases retinal ganglion cell genesis [1].
• Finally, we demonstrate that induction of VEGF and Ang2a expression by Shh in normal limb buds is accompanied by vascular remodelling [15].
• VEGF coordinates interaction of pericytes and endothelial cells during vasculogenesis and experimental angiogenesis [19].
• In vivo, VEGF-induced elongation and migration of desmin-positive pericytes and coverage of angiogenic capillaries, as revealed by analysis of Sambucus nigra lectin-stained vascular beds of the chick chorioallantoic membrane [19].

Associations of VEGFA with chemical compounds

• In a differential display screening for genes regulated by retinoic acid in the developing chick limb bud, we have isolated a novel gene, termed rigf, retinoic-acid induced growth factor, that encodes a protein belonging to the vascular endothelial growth factor (VEGF) family [20].
• We also demonstrated that VEGF was involved in CHO-ET-1-mediated angiogenesis, by using a specific inhibitor of VEGF tyrosine kinase receptor activity (PTK787/ZK 222584), which abolished CHO-ET-1 nodule formation and CAM neovascularization [21].
• CONCLUSIONS: The findings suggest that the induction of angiogenesis and VEGF expression by ethanol represents an important mechanism of cancer progression associated with alcoholic beverage consumption [13].
• PGE2 dose-dependently inhibited the expression of the differentiation-related genes, colX, VEGF, MMP-13, and alkaline phosphatase gene, and enzyme activity with significant effects at concentrations as low as 10(-10) M [22].
• Apigenin inhibits tumor angiogenesis through decreasing HIF-1{alpha} and VEGF expression [12].

Regulatory relationships of VEGFA

• These observations are in accordance with the proposal that Ang-2 induces angiogenesis in the presence of VEGF and vascular regression in its absence [23].

Other interactions of VEGFA

• Furthermore, although the capillary network initiated by VEGF and b-FGF lasts no more than 7 days, addition of a sulfated oligosaccharide significantly amplifies angiogenesis and stabilizes the capillary network of new blood vessels [24].
• This paper describes the expression of VEGF and of VEGFR-2 in the vasculature of the chorioallantoic membrane (CAM) as revealed by in situ hybridization and immunoelectron microscopy [25].
• Testicular regression is accompanied by high expression of Ang-2 and very low expression of VEGF [23].
• VEGF release kinetics from scCO(2)-VEGF incorporated PLA monolith scaffolds showed a cumulative release of VEGF (2837+/-761rhog/ml) over a 21 day period in culture [26].
• Furthermore, we cloned a novel FGF receptor-like molecule as well as two novel putative RTKs related to the vascular endothelial growth factor (VEGF) receptor [27].

Analytical, diagnostic and therapeutic context of VEGFA

• VEGF levels were quantified using ELISA [2].
• Conditioned medium was analyzed using Western blots for HIF-1alpha or VEGF [2].
• Several embryonic stages (e 13.5, 16, 19, and 20) are examined by means of light microscopy, electron microscopy (TEM), and immunohistochemistry (VEGF, type I and II collagen) [28].
• Electron microscopy demonstrated that VEGF-overexpressing cells modified the phenotype of the endothelium of the blood vessels at the boundary between the implant and the surrounding CAM mesenchyme [29].
• VEGF mRNA and protein were determined by Northern blot analysis and enzyme-linked immunosorbent assay [13].

References