COMP-Ang1: a designed angiopoietin-1 variant with nonleaky angiogenic activity.
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.
Cho
Chung-Hyun
CH
Biomedical Research Center and Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea.
Kammerer
Richard A
RA
Lee
Hyuek Jong
HJ
Steinmetz
Michel O
MO
Ryu
Young Shin
YS
Lee
Sung Ho
SH
Yasunaga
Kunio
K
Kim
Kyung-Tae
KT
Kim
Injune
I
Choi
Han-Ho
HH
Kim
Won
W
Kim
Sung Hyun
SH
Park
Sung Kwang
SK
Lee
Gyun Min
GM
Koh
Gou Young
GY
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
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