title: COMP-Ang1: a designed angiopoietin-1 variant with nonleaky angiogenic activity.
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.
authors.affiliation: Biomedical Research Center and Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea.
authors.forename: Chung-Hyun
authors.initials: CH
authors.lastname: Cho
authors.forename: Richard A
authors.initials: RA
authors.lastname: Kammerer
authors.forename: Hyuek Jong
authors.initials: HJ
authors.lastname: Lee
authors.forename: Michel O
authors.initials: MO
authors.lastname: Steinmetz
authors.forename: Young Shin
authors.initials: YS
authors.lastname: Ryu
authors.forename: Sung Ho
authors.initials: SH
authors.lastname: Lee
authors.forename: Kunio
authors.initials: K
authors.lastname: Yasunaga
authors.forename: Kyung-Tae
authors.initials: KT
authors.lastname: Kim
authors.forename: Injune
authors.initials: I
authors.lastname: Kim
authors.forename: Han-Ho
authors.initials: HH
authors.lastname: Choi
authors.forename: Won
authors.initials: W
authors.lastname: Kim
authors.forename: Sung Hyun
authors.initials: SH
authors.lastname: Kim
authors.forename: Sung Kwang
authors.initials: SK
authors.lastname: Park
authors.forename: Gyun Min
authors.initials: GM
authors.lastname: Lee
authors.forename: Gou Young
authors.initials: GY
authors.lastname: Koh
mesh_terms: D000595:Amino Acid Sequence; D043924:Angiogenesis Modulating Agents / Q000737:chemistry / Q000494:pharmacology*; D042683:Angiopoietin-1 / Q000737:chemistry / Q000235:genetics* / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D064236:Cartilage Oligomeric Matrix Protein; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D003315:Cornea / Q000098:blood supply; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D016326:Extracellular Matrix Proteins / Q000737:chemistry / Q000235:genetics*; D006023:Glycoproteins / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D008297:Male; D064235:Matrilin Proteins; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D010766:Phosphorylation; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D051381:Rats; D042787:Receptor, TIE-2 / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology; D014471:Umbilical Veins / Q000166:cytology / Q000187:drug effects
chemical_list: D043924:Angiogenesis Modulating Agents; D042683:Angiopoietin-1; C515576:COMP-Ang1 fusion protein; D064236:Cartilage Oligomeric Matrix Protein; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; C577540:Matn1 protein, mouse; D064235:Matrilin Proteins; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; C577553:TSP5 protein, human; D042787:Receptor, TIE-2