Molecular and Biological Properties of the Vascular Endothelial Growth Factor Family of Proteins

Ferrara, Napoleone; Houck, Keith A.; Jakeman, Lyn B.; Leung, David W. M.

doi:10.1210/edrv-13-1-18

Cited by 1,415 publications

(450 citation statements)

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“…Among the various angiogenic factors identified to date, VEGF is unique because it specifically acts on endothelial cells (Connolly, 1991;Ferrara et al, 1992) and its cell-surface receptors are exclusively expressed in endothelial cells Plate et al, 1993). The overexpression of VEGF and its receptors are associated with chronic inflammation, tumour growth and other angiogenic diseases.…”

Section: Discussionmentioning

confidence: 99%

“…However, vascular endothelial growth factor (VEGF) has attracted much attention recently because it is the only angiogenic factor that specifically acts on endothelial cells (Connolly, 1991;Ferrara et al, 1992;Senger et al, 1993). The isolation of VEGF from several tumour cell lines and macrophages has implicated it as a major tumour angiogenesis factor in some human gliomas Author for correspondence.…”

Section: Introductionmentioning

confidence: 99%

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Suppression of VEGF‐induced angiogenesis by the protein tyrosine kinase inhibitor, lavendustin A

Fan

1995

British J Pharmacology

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3 Daily local administration of 250 ng VEGF165 accelerated the rate of "33Xe clearance from the sponges and induced an intense neovascularisation. This VEGF165-induced angiogenesis was inhibited by daily co-administration of the selective PTK inhibitor, lavendustin A (10 jig), but not its negative control, lavendustin B (10 jig). Blood flow measurements and morphometric analysis of 8-day-old sponges showed that lavendustin A reduced the "33Xe clearance of VEGF165-treated sponges from 32.9 ± 1.5% to 20.9 ± 1.6% and the total fibrovascular growth area from 62.4 ± 6.1% to 21.6 ± 6.8% (n = 1 2, P < 0.05). 4 Co-injection of suramin (3 mg), an inhibitor of heparin-binding growth factors, also suppressed the VEGF165-elicited neovascular response. In contrast, neither lavendustin A nor suramin produced any effect on the basal sponge-induced angiogenesis. 5 When given alone, low doses of VEGF 165 (25 ng) or basic fibroblast growth factor (bFGF; 10 ng) did not modify the basal sponge-induced neovascularisation. However, co-administration of these two peptides to a single sponge together caused a significant increase in the rate of '33Xe clearance and angiogenesis similar to that seen with the high dose of VEGF165 (250 ng) acting alone. This VEGF/ bFGF neovascular response was also blocked by daily co-administration of lavendustin A (10 jig), suramin (3 mg) or a monoclonal anti-bFGF antibody (DG2, I jig), but not lavendustin B (10 g). 6 These results suggest that selective inhibition of PTK could have therapeutic potential in angiogenic diseases where VEGF plays a dominant role. Furthermore, blockade of the angiogenic activity of VEGF and VEGF,/bFGF by suramin reveals an alternative strategy in angiosuppression.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Suppression of VEGF‐induced angiogenesis by the protein tyrosine kinase inhibitor, lavendustin A

Fan

1995

British J Pharmacology

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“…4, the anti-AGE-RNase A antiserum was found to completely neutralize the AGE-induced synthesis of endothelial cell DNA at 1%, while the same concentration of the antiserum did not affect DNA synthesis in endothelial cells not exposed to AGE-BSA. (29,30). Since Northern blot analysis cannot clearly discriminate the four mRNA species, we employed a more sensitive RT-PCR technique as described previously (20).…”

Section: Stimulation Of the Growth Of Microvascular Endothelialmentioning

confidence: 99%

Advanced Glycation End Products-driven Angiogenesis in Vitro

Yamagishi

Yonekura

Yamamoto

et al. 1997

Journal of Biological Chemistry

260

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This study was undertaken to determine whether and how advanced glycation end products (AGE), senescent macroproteins accumulated in various tissues under hyperglycemic states, cause angiogenesis, the principal vascular derangement in diabetic microangiopathy. We first prepared AGE-bovine serum albumin (BSA) and anti-AGE antiserum using AGE-RNase A. Then AGE-BSA was administered to human skin microvascular endothelial cells in culture, and their growth was examined. The AGE-BSA, but not nonglycated BSA, was found to induce a statistically significant increase in the number of viable endothelial cells as well as their synthesis of DNA. The increase in DNA synthesis by AGE-BSA was abolished by anti-AGE antibodies. AGE-BSA also stimulated the tube formation of endothelial cells on Matrigel. We obtained the following evidence that it is vascular endothelial growth factor (VEGF) that mainly mediates the angiogenic activities of AGE. Glucose and other reducing sugars can react nonenzymatically with the amino groups of proteins to form reversible Schiff bases and, then, Amadori products. These early glycation products undergo further complex reactions such as rearrangement, dehydration, and condensation to become irreversibly crosslinked, heterogeneous fluorescent derivatives termed advanced glycation end products (AGE) 1 (1). The formation and accumulation of AGE in various tissues have been known to progress during normal aging and at an extremely accelerated rate in diabetes mellitus. This has been implicated in the development of diabetic micro-and macro-vascular complications (1), which may account for the disabilities and high mortality rate in patients with this disease (2).Microvessels are composed of only two types of cells, endothelial cells and pericytes, and have been known to show both functional and structural abnormalities during prolonged diabetic exposure, resulting in the deleterious effects on the organs that they supply (3-5). Using pericyte-endothelial cell co-culture systems, we have shown previously that pericytes can not only regulate the growth but also preserve the prostacyclin-producing ability and protect against lipid peroxide-induced injury of endothelial cells (6). This has provided a basis for understanding how diabetic retinopathy develops consequent to "pericyte loss," the earliest histopathological hallmark in diabetic retinopathy (5, 7).Recently, we have found that AGE exert a growth inhibitory effect and a cell type-specific immediate toxicity on pericytes through interactions with their receptor for AGE (RAGE), a cell surface receptor belonging to the immunoglobulin superfamily (8), and have proposed a novel mechanism for pericyte loss (9). The AGE-induced, RAGE-mediated decrease in pericyte number would then indirectly cause angiogenesis (6,9).In the present study, we investigated the effects of AGE on the growth and tube formation of human skin microvascular endothelial cells, the key steps of angiogenesis. We demonstrate that AGE exert angiogenic activities directly on microvasc...

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“…cyte migration, vascular permeability, and procoagulant functions in endothelium (34,35). Moreover, the presence of significant VEGF mRNA and protein in various tissues of the adult suggests an additional role for VEGF in the maintenance of normal vascular cell integrity and/or behavior (4).…”

Section: Fig 7 Analysis Of the Mouse Vegf 3 -Endmentioning

confidence: 99%