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.

Neovasculature induced by vascular endothelial growth factor is fenestrated.

Abstract: We have reported previously that topical administration of vascular endothelial growth factor165 (VEGF) to a microvascular bed supplied with a continuous endothelium can rapidly induce the formation of endothelial fenestrations (W. G. Roberts and G. E. Palade, J. Cell Sci., 108: 2369-2379, 1995). From these results, we hypothesized that tumor vasculature, in general, may also be fenestrated because it has been reported that tumor secretion of VEGF causes the surrounding host vasculature to invade and feed the growing tumor. Using electron microscopy to characterize the endothelial cell morphology in tumor vessels from either the periphery or the core of the tumor and immunoblotting to detect secreted VEGF, we analyzed the vasculature of human and murine neoplastic tumors grown s.c. in male nude mice. To clarify the role of VEGF165 two models were used: (a) Chinese hamster ovary (CHO) cells stably transfected with hu VEGF165 and injected into mice (VEGF:CHO tumors); and (b) slow-release pellets containing purified VEGF or basic fibroblast growth factor implanted on the rat cremaster muscle. All tumors had vessels with fenestrated endothelium, open interendothelial junctions, and clustered fused caveolae. From all of the peripheral tumor vessels observed, fenestrated endothelium was observed in 41% from EMT, 35% from M1S, 37% from U87, and 56% from VEGF:CHO tumors, whereas surrounding skin and muscle, from which tumor vessels were derived, had fenestrated endothelium in 2 and 0% of all vessels, respectively. Additionally, further analysis revealed a substantial decrease in the anionic glycocalyx on the luminal face of the fenestral diaphragms in endothelium from tumors (especially VEGF:CHO) when compared to intestine or pancreas. Because the host tissue microvascular endothelium which supplies the tumor is not fenestrated, tumors can transform nonproliferating, nonfenestrated vessels into proliferating vessels, many of which have fenestrated endothelium. These data provide evidence that chronic VEGF exposure can induce fenestrations in nonfenestrated endothelium similar to the fenestrated endothelium found in tumor vessels.

Potentiated angiogenic effect of scatter factor/hepatocyte growth factor via induction of vascular endothelial growth factor: the case for paracrine amplification of angiogenesis

Abstract: Background —Scatter factor/hepatocyte growth factor (SF/HGF) is a pleiotropic growth factor that stimulates proliferation and migration of endothelial cells (ECs) via the c- Met receptor, present on ECs as well as other cell types, including smooth muscle cells (SMCs). We studied the effects of recombinant human (rh) SF/HGF in vitro and in vivo in a rabbit model of hindlimb ischemia. We further compared these effects with those of recombinant human vascular endothelial growth factor (rhVEGF 165 ), an EC–specific mitogen. Methods and Results —In vitro, rhSF/HGF and rhVEGF 165 exhibited similar effects on proliferation and migration of ECs. When both cytokines were administered together, the result was an additive effect on EC proliferation and a synergistic effect on EC migration. Application of rhSF/HGF to cultures of human SMCs resulted in the induction of VEGF mRNA and protein. In vivo, administration of rhSF/HGF (500 μg×3) was associated with significant improvements in collateral formation ( P P P 165 administered according to the same protocol ( P 165 . Conclusions —The pleiotropic effects of certain growth factors may potentiate angiogenesis via a combination of direct effects on EC proliferation and migration and indirect effects that result in the generation of other potent EC mitogens from non-EC populations. The synergistic effects demonstrated when SF/HGF and VEGF are administered together in vitro may be reproduced in vivo by SF/HGF-induced upregulation of VEGF in vascular SMCs.

Deletion of vascular endothelial growth factor in myeloid cells accelerates tumorigenesis

Abstract: Angiogenesis and the development of a vascular network are required for tumour progression, and they involve the release of angiogenic factors, including vascular endothelial growth factor (VEGF-A), from both malignant and stromal cell types Infiltration by cells of the myeloid lineage is a hallmark of many tumours, and in many cases the macrophages in these infiltrates express VEGF-A Here we show that the deletion of inflammatory-cell-derived VEGF-A attenuates the formation of a typical high-density vessel network, thus blocking the angiogenic switch in solid tumours in mice Vasculature in tumours lacking myeloid-cell-derived VEGF-A was less tortuous, with increased pericyte coverage and decreased vessel length, indicating vascular normalization In addition, loss of myeloid-derived VEGF-A decreases the phosphorylation of VEGF receptor 2 (VEGFR2) in tumours, even though overall VEGF-A levels in the tumours are unaffected However, deletion of myeloid-cell VEGF-A resulted in an accelerated tumour progression in multiple subcutaneous isograft models and an autochthonous transgenic model of mammary tumorigenesis, with less overall tumour cell death and decreased tumour hypoxia Furthermore, loss of myeloid-cell VEGF-A increased the susceptibility of tumours to chemotherapeutic cytotoxicity This shows that myeloid-derived VEGF-A is essential for the tumorigenic alteration of vasculature and signalling to VEGFR2, and that these changes act to retard, not promote, tumour progression