Vascular endothelial growth factor A

About: Vascular endothelial growth factor A is a research topic. Over the lifetime, 15203 publications have been published within this topic receiving 1271498 citations. The topic is also known as: vascular endothelial growth factor A & vascular endothelial growth factor A165.

Rapid induction of vascular endothelial growth factor gene expression after transient middle cerebral artery occlusion in rats.

Abstract: Background and Purpose Vascular endothelial growth factor (VEGF) is a mitogen for endothelial cells and also has the potential to increase vascular permeability. Therefore, it may contribute to the recovery of brain cells from ischemic insult through potentiating neovascularization or may exacerbate brain damage by forming brain edema. However, the exact role of this protein in cerebral ischemia is not fully understood. We investigated temporal, spatial, and cellular profiles of the induction of VEGF gene expression after transient focal cerebral ischemia at both mRNA and protein levels. Methods We used a transient middle cerebral artery (MCA) occlusion model. Northern blot analysis was performed to assess the chronological pattern of induction and the impact of length of ischemia on mRNA expression. Western blot analysis was performed to ensure the selective detection of immunoreactive VEGF with an antibody. Temporal, spatial, and cellular changes of immunohistochemical VEGF expression were compared with...

Cooperative effect of TNFalpha, bFGF, and VEGF on the formation of tubular structures of human microvascular endothelial cells in a fibrin matrix. Role of urokinase activity.

Abstract: In angiogenesis associated with tissue repair and disease, fibrin and inflammatory mediators are often involved. We have used three-dimensional fibrin matrices to investigate the humoral requirements of human microvascular endothelial cells (hMVEC) to form capillary-like tubular structures. bFGF and VEGF165 were unable to induce tubular structures by themselves. Simultaneous addition of one or both of these factors with TNFalpha induced outgrowth of tubules, the effect being the strongest when bFGF, VEGF165, and TNFalpha were added simultaneously. Exogenously added u-PA, but not its nonproteolytic amino-terminal fragment, could replace TNFalpha, suggesting that TNFalpha-induced u-PA synthesis was involved. Soluble u-PA receptor (u-PAR) or antibodies that inhibited u-PA activity prevented the formation of tubular structures by 59-99%. epsilon-ACA and trasylol which inhibit the formation and activity of plasmin reduced the extent of tube formation by 71-95%. TNFalpha or u-PA did not induce tubular structures without additional growth factors. bFGF and VEGF165 enhanced of the u-PAR by 72 and 46%, but TNFalpha itself also increased u-PAR in hMVEC by 30%. Induction of mitogenesis was not the major contribution of bFGF and VEGF165 because the cell number did not change significantly in the presence of TNFalpha, and tyrphostin A47, which inhibited mitosis completely, reduced the formation of tubular structures only by 28-36%. These data show that induction of cell-bound u-PA activity by the cytokine TNFalpha is required in addition to the angiogenic factors VEGF165 and/or bFGF to induce in vitro formation of capillary-like structures by hMVEC in fibrin matrices. These data may provide insight in the mechanism of angiogenesis as occurs in pathological conditions.

EGCG, a major component of green tea, inhibits tumour growth by inhibiting VEGF induction in human colon carcinoma cells.

Abstract: Catechins are key components of teas that have antiproliferative properties. We investigated the effects of green tea catechins on intracellular signalling and VEGF induction in vitro in serum-deprived HT29 human colon cancer cells and in vivo on the growth of HT29 cells in nude mice. In the in vitro studies, (-)-epigallocatechin gallate (EGCG), the most abundant catechin in green tea extract, inhibited Erk-1 and Erk-2 activation in a dose-dependent manner. However, other tea catechins such as (-)-epigallocatechin (EGC), (-)-epicatechin gallate (ECG), and (-)-epicatechin (EC) did not affect Erk-1 or 2 activation at a concentration of 30 μM. EGCG also inhibited the increase of VEGF expression and promoter activity induced by serum starvation. In the in vivo studies, athymic BALB/c nude mice were inoculated subcutaneously with HT29 cells and treated with daily intraperitoneal injections of EC (negative control) or EGCG at 1.5 mg day−1mouse−1starting 2 days after tumour cell inoculation. Treatment with EGCG inhibited tumour growth (58%), microvessel density (30%), and tumour cell proliferation (27%) and increased tumour cell apoptosis (1.9-fold) and endothelial cell apoptosis (3-fold) relative to the control condition (P< 0.05 for all comparisons). EGCG may exert at least part of its anticancer effect by inhibiting angiogenesis through blocking the induction of VEGF. © 2001 Cancer Research Campaign http://www.bjcancer.com

Influence of Photodynamic Therapy on Expression of Vascular Endothelial Growth Factor (VEGF), VEGF Receptor 3, and Pigment Epithelium–Derived Factor

Abstract: Purpose To evaluate the impact of photodynamic therapy (PDT) on expression and distribution of vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR)-3, and pigment epithelium-derived factor (PEDF). Methods Eyes of patients scheduled for enucleation due to untreatable malignancy served as study eyes (n = 4), age-matched donor eyes were used as the control (n = 4). PDT using verteporfin with the recommended standard parameters was applied to intact areas of the perimacular region. Lesions were classified by ophthalmoscopy, fluorescein angiography (FA), and indocyanine green angiography (ICGA), as well as light and electron microscopic (LM/EM) histology. Immunolabeling using specific antibodies against VEGF, VEGFR-3, and PEDF was performed in PDT-treated areas, untreated collateral areas in study eyes, and untreated areas of control eyes. Specimens were fixed in 4% paraformaldehyde and 1% glutaraldehyde and embedded in paraffin. Four-micrometer-thick sections were stained using the peroxidase-labeled streptavidin-biotin method. Results All PDT-treated areas demonstrated characteristic choroidal hypofluorescence by FA and ICGA. LM/EM histology revealed selective damage of choriocapillary endothelial cells. VEGF was expressed in the endothelial layer of choriocapillaries and focally within larger choroidal vessels in treated areas, but not in untreated areas. Sites with positive VEGF labeling also demonstrated upregulation of VEGFR-3. PEDF expression was localized to retinas in all eyes; however, PEDF staining of choroidal endothelial cells was specific for treated areas of study eyes. Conclusions PDT using verteporfin induces a reproducible angiogenic response in elderly human eyes. VEGF, VEGFR-3, and PEDF expression is enhanced after PDT. Choroidal endothelial cells appear to be the primary site of angiogenic stimulation.