Cooperative interaction of Angiopoietin-like proteins 1 and 2 in vascular development

Yoshiaki Kubota, Yuichi Oike, Shinya Satoh, Yoko Tabata, Yuichi Niikura, Tohru Morisada, Masaki Akao, Takashi Urano, Yasuhiro Ito, Takeshi Miyamoto, Norihiro Nagai, Gou Young Koh, Sumiko Watanabe, Toshio Suda

Research output: Contribution to journalArticlepeer-review

88 Citations (Scopus)


Angiopoietin-like protein (Angptl) 1 and Angptl2, which are considered orphan ligands, are highly homologous, particularly in the fibrinogen-like domain containing the putative receptor binding site. This similarity suggests potentially cooperative functions between the two proteins. In this report, the function of Angptl1 and Angptl2 is analyzed by using morpholino antisense technology in zebrafish. Knockdown of both Angptl1 and Angptl2 produced severe vascular defects due to increased apoptosis of endothelial cells at the sprouting stage. In vitro studies showed that Angptl1 and Angptl2 have antiapoptotic activities through the phosphatidylinositol 3-kinase Akt pathway, and coinjection of constitutively active Akt/protein kinase B mRNA rescued impaired vascular development seen in double knockdown embryos. These results provide a physiological demonstration of the cooperative interaction of Angptl1 and Angptl2 in endothelial cells through phosphatidylinositol 3-kinase/Akt mediated antiapoptotic activities.

Original languageEnglish
Pages (from-to)13502-13507
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number38
Publication statusPublished - Sept 20 2005
Externally publishedYes


  • Akt
  • Angiogenesis
  • Apoptosis
  • Morpholino
  • Phosphatidylinositol 3-kinase

ASJC Scopus subject areas

  • General


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