Abstract
Angiopoietin-1 (Ang1) has potential therapeutic applications in inducing angiogenesis, enhancing endothelial cell survival, and preventing vascular leakage. However, production of Ang1 is hindered by aggregation and insolubility resulting from disulfide-linked higher-order structures. Here, by replacing the N-terminal portion of Ang1 with the short coiled-coil domain of cartilage oligomeric matrix protein (COMP), we have generated a soluble, stable, and potent Ang1 variant, COMP-Ang1. This variant is more potent than native Ang1 in phosphorylating the tyrosine kinase with Ig and epidermal growth factor homology domain 2 (Tie2) receptor and Akt in primary cultured endothelial cells, enhancing angiogenesis in vitro and increasing adult angiogenesis in vivo. Thus, COMP-Ang1 is an effective alternative to native Ang1 for therapeutic angiogenesis in vivo.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Angiogenesis Modulating Agents / chemistry
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Angiogenesis Modulating Agents / pharmacology*
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Angiopoietin-1 / chemistry
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Angiopoietin-1 / genetics*
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Angiopoietin-1 / pharmacology*
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Animals
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Apoptosis / drug effects
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Cartilage Oligomeric Matrix Protein
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Cell Movement / drug effects
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Cells, Cultured
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Cornea / blood supply
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Endothelium, Vascular / cytology
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Endothelium, Vascular / drug effects
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Extracellular Matrix Proteins / chemistry
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Extracellular Matrix Proteins / genetics*
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Glycoproteins / chemistry
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Glycoproteins / genetics*
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Humans
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Male
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Matrilin Proteins
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Mice
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Mice, Inbred Strains
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Molecular Sequence Data
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Phosphorylation
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Protein Structure, Quaternary
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Protein Structure, Tertiary
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Rats
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Receptor, TIE-2 / metabolism
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Recombinant Fusion Proteins / chemistry
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / pharmacology
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Recombinant Proteins / chemistry
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Recombinant Proteins / genetics
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Recombinant Proteins / pharmacology
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Umbilical Veins / cytology
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Umbilical Veins / drug effects
Substances
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Angiogenesis Modulating Agents
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Angiopoietin-1
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COMP-Ang1 fusion protein
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Cartilage Oligomeric Matrix Protein
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Extracellular Matrix Proteins
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Glycoproteins
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Matn1 protein, mouse
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Matrilin Proteins
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Recombinant Fusion Proteins
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Recombinant Proteins
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TSP5 protein, human
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Receptor, TIE-2