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.
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Authors | A Pedram, M Razandi, R M Hu, E R Levin |
Journal | The Journal of biological chemistry
(J Biol Chem)
Vol. 272
Issue 27
Pg. 17097-103
(Jul 04 1997)
ISSN: 0021-9258 [Print] United States |
PMID | 9202027
(Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Endothelial Growth Factors
- Endothelin-1
- Endothelin-3
- Lymphokines
- Protein Sorting Signals
- Proteins
- RNA, Messenger
- Receptors, Endothelin
- Vascular Endothelial Growth Factor A
- Vascular Endothelial Growth Factors
- Natriuretic Peptide, C-Type
- Atrial Natriuretic Factor
- GTP-Binding Proteins
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Topics |
- Animals
- Atrial Natriuretic Factor
(metabolism)
- Cattle
- Cell Division
- Endothelial Growth Factors
(biosynthesis, genetics)
- Endothelin-1
(metabolism)
- Endothelin-3
(metabolism)
- Endothelium, Vascular
(cytology, metabolism)
- GTP-Binding Proteins
(metabolism)
- Humans
- Lymphokines
(biosynthesis, genetics)
- Muscle, Smooth, Vascular
(cytology, 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
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