COMP-Ang1: A designed angiopoietin-1 variant with nonleaky angiogenic activity
AUTOR(ES)
Cho, Chung-Hyun
FONTE
National Academy of Sciences
RESUMO
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.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=397420Documentos Relacionados
- Designed angiopoietin-1 variant, COMP-Ang1, protects against radiation-induced endothelial cell apoptosis
- Contrasting Actions of Selective Inhibitors of Angiopoietin-1 and Angiopoietin-2 on the Normalization of Tumor Blood Vessels
- Mast cell–derived angiopoietin-1 plays a critical role in the growth of plasma cell tumors
- Angiopoietin-1 modulates endothelial cell function and gene expression via the transcription factor FKHR (FOXO1)
- Recombinant angiopoietin-1 restores higher-order architecture of growing blood vessels in mice in the absence of mural cells