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PMID:9202027

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Citation

Pedram, A, Razandi, M, Hu, RM and Levin, ER (1997) Vasoactive peptides modulate vascular endothelial cell growth factor production and endothelial cell proliferation and invasion. J. Biol. Chem. 272:17097-103

Abstract

The proliferation of vascular endothelial cells (EC) is an important event in angiogenesis. The synthesis of the EC growth factor, vascular endothelial cell growth factor (VEGF), is stimulated by a variety of activators; but the effects of important vasoactive peptides are not well understood, and there are no known natural inhibitors of VEGF production. We found that the vasoactive peptides endothelin (ET)-1 and ET-3 stimulated the synthesis of VEGF protein 3-4-fold in cultured human vascular smooth muscle cells, comparable in magnitude to hypoxia. ET-1 and ET-3 acted through the ETA and ETB receptors, respectively, and signaling through protein kinase C was important. Atrial natriuretic peptide (ANP), C-type natriuretic peptide, and C-ANP-(4-23), a ligand for the natriuretic peptide clearance receptor, equipotently inhibited production of VEGF by as much as 88% and inhibited ET- or hypoxia-stimulated VEGF transcription. EC proliferation and invasion of matrix were stimulated by VEGF secreted into the medium by ET-incubated vascular smooth muscle cells. This was inhibited by ANP. Our results identify the natriuretic peptides as the first peptide inhibitors of VEGF synthesis and indicate a novel mechanism by which vasoactive peptides could modulate angiogenesis.

Links

PubMed

Keywords

Animals; Atrial Natriuretic Factor/metabolism; Cattle; Cell Division; Endothelial Growth Factors/biosynthesis; Endothelial Growth Factors/genetics; Endothelin-1/metabolism; Endothelin-3/metabolism; Endothelium, Vascular/cytology; Endothelium, Vascular/metabolism; GTP-Binding Proteins/metabolism; Humans; Lymphokines/biosynthesis; Lymphokines/genetics; Muscle, Smooth, Vascular/cytology; Muscle, Smooth, Vascular/metabolism; Natriuretic Peptide, C-Type; Neovascularization, Physiologic; Protein Biosynthesis; Protein Sorting Signals/metabolism; Proteins/metabolism; RNA, Messenger/metabolism; Receptors, Endothelin/metabolism; Transcription, Genetic; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:VEGFA

located_in

GO:0005615: extracellular space

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:VEGFA

involved_in

GO:0043536: positive regulation of blood vessel endothelial cell migration

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:VEGFA

involved_in

GO:0001938: positive regulation of endothelial cell proliferation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:VEGFA

part_of

GO:0005615: extracellular space

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:VEGFA

enables

GO:0008083: growth factor activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete


See also

References

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