COMP-Ang1: a designed angiopoietin-1 variant with nonleaky angiogenic activity |
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Authors: | Cho Chung-Hyun Kammerer Richard A Lee Hyuek Jong Steinmetz Michel O Ryu Young Shin Lee Sung Ho Yasunaga Kunio Kim Kyung-Tae Kim Injune Choi Han-Ho Kim Won Kim Sung Hyun Park Sung Kwang Lee Gyun Min Koh Gou Young |
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Institution: | Biomedical Research Center and Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea. |
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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. |
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