Abstract
Angiogenesis is a process modulated by several endogenous vascular growth factors as well as by oxygen conditions. For example VEGF failed to induce useful therapeutic angiogenesis in clinical trials. We used a combinatory phage display peptide library screening on human umbilical endothelial cells under normoxia and hypoxia conditions in order to identify novel peptides that bind endothelial cells. The identified peptides induced angiogenesis as demonstrated by endothelial cell proliferation, migration and tube formation. Injection of peptides into the ears of mice resulted in increased numbers of blood vessels. Peptides did not induce VEGF receptor gene expression indicating a possible VEGF unrelated mechanism.
MeSH terms
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Amino Acid Sequence
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Animals
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Cell Hypoxia
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Cell Movement / drug effects
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Cell Proliferation / drug effects
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Cells, Cultured
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Drug Evaluation, Preclinical
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Endothelial Cells / drug effects*
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Endothelial Cells / physiology
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Gene Expression / drug effects
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Humans
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In Vitro Techniques
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Mice
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Mice, Inbred BALB C
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Neovascularization, Physiologic / drug effects*
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Neovascularization, Physiologic / genetics
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Neovascularization, Physiologic / physiology
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Oligopeptides / chemistry
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Oligopeptides / pharmacology*
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Peptide Library
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Vascular Endothelial Growth Factor Receptor-1 / genetics
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Vascular Endothelial Growth Factor Receptor-2 / genetics
Substances
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Oligopeptides
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Peptide Library
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FLT1 protein, human
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Vascular Endothelial Growth Factor Receptor-1
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Vascular Endothelial Growth Factor Receptor-2