Peptides encoded by exon 6 of VEGF inhibit endothelial cell biological responses and angiogenesis induced by VEGF

Autor: David L. Selwood, Dana Davis, Haiyan Jia, Sylvie Jezequel, Shay Soker, Shaheda Shaikh, Marianne Löhr, Ian Zachary
Rok vydání: 2001
Předmět:
Vascular Endothelial Growth Factor A
Angiogenesis
Cell Survival
Swine
Biophysics
Neovascularization
Physiologic
Angiogenesis Inhibitors
Nerve Tissue Proteins
Endothelial Growth Factors
Biology
Biochemistry
Binding
Competitive
Neovascularization
Exon
chemistry.chemical_compound
Cell Movement
Proto-Oncogene Proteins
Neuropilin 1
medicine
Animals
Humans
Receptors
Growth Factor
Receptor
Molecular Biology
Cells
Cultured
Lymphokines
Vascular Endothelial Growth Factor Receptor-1
Vascular Endothelial Growth Factors
Receptor Protein-Tyrosine Kinases
Cell Biology
Exons
Fibroblasts
Coculture Techniques
Neuropilin-1
Peptide Fragments
Vascular endothelial growth factor
Endothelial stem cell
Vascular endothelial growth factor A
Receptors
Vascular Endothelial Growth Factor
chemistry
cardiovascular system
Cancer research
Fibroblast Growth Factor 2
Endothelium
Vascular
medicine.symptom
Mitogen-Activated Protein Kinases
Cell Division
Protein Binding
Zdroj: Biochemical and biophysical research communications. 283(1)
ISSN: 0006-291X
Popis: 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.
Databáze: OpenAIRE
Externí odkaz: