Peptides encoded by exon 6 of VEGF inhibit endothelial cell biological responses and angiogenesis induced by VEGF.
Biochem Biophys Res Commun
; 283(1): 164-73, 2001 Apr 27.
Article
in En
| MEDLINE
| ID: mdl-11322784
ABSTRACT
VEGF induces pathological angiogenesis and is an important target for the development of novel antiangiogenic molecules. In this study, we tested synthetic peptides based on the sequence of VEGF(189) for their ability to inhibit VEGF receptor binding and biological responses. We identified 12-amino acid peptides derived from exon 6 that inhibited VEGF binding to HUVECs, VEGF-stimulated ERK activation, and prostacyclin production. These peptides inhibited VEGF-induced mitogenesis, migration, and VEGF-dependent survival of endothelial cells, but caused no increase in apoptosis in the absence of VEGF. Exon 6-encoded peptides also caused a marked inhibition of VEGF-induced angiogenesis in vitro. Studies of effects of peptides on cross-linking of VEGF to its receptors and on binding of VEGF to porcine aortic endothelial cells expressing either KDR or neuropilin-1 showed that exon 6-encoded peptides effectively blocked the interaction of VEGF with both receptors. Exon 6-derived peptides caused release of bFGF from endothelial cells but inhibited bFGF-dependent ERK activation, cell proliferation and angiogenesis. Our findings indicate that VEGF exon 6-encoded peptides inhibit VEGF-induced angiogenesis, at least in part through inhibition of VEGF binding to KDR. In addition, exon 6-encoded peptides are also effective inhibitors of bFGF-mediated angiogenesis.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Peptide Fragments
/
Endothelium, Vascular
/
Endothelial Growth Factors
/
Lymphokines
/
Neovascularization, Physiologic
Type of study:
Prognostic_studies
Language:
En
Journal:
Biochem Biophys Res Commun
Year:
2001
Document type:
Article
Affiliation country:
Reino Unido