Tie1 controls angiopoietin function in vascular remodeling and inflammation

• DOI: 10.1172/jci84923
• Publication Date: 2016-08-21T22:00:33Z
• Authors: Emilia A. Korhonen; Anita Lampinen; Hemant Giri; Andrey Anisimov; Minah Kim; Breanna Allen; Shentong Fang; Gabriela D’Amico; Tuomas J. Sipilä; Marja Lohela; Tomas Strandin; Antti Vaheri; Seppo Ylä-Herttuala; Gou Young Koh; Donald M. McDonald; Kari Alitalo; Pipsa Saharinen
• Keywords: Angiopoietin receptor; Angiopoietin

The angiopoietin/Tie (ANG/Tie) receptor system controls developmental and tumor angiogenesis, inflammatory vascular remodeling, vessel leakage. ANG1 is a Tie2 agonist that promotes stabilization in inflammation sepsis, whereas ANG2 context-dependent or antagonist. A limited understanding of ANG signaling mechanisms the orphan Tie1 has hindered development ANG/Tie-targeted therapeutics. Here, we determined both binding to increases Tie1-Tie2 interactions β1 integrin-dependent manner regulates ANG-induced trafficking endothelial cells. Endothelial was essential for activity autocrine ANG2. Deletion mice reduced phosphorylation downstream Akt activation, increased FOXO1 nuclear localization transcriptional prevented ANG1- ANG2-induced capillary-to-venous remodeling. However, acute endotoxemia, ectodomain responsible interaction with rapidly cleaved, decreased, lost, which led suppression signaling. cleavage also occurred patients hantavirus infection. These results support model directly interacts promote responses under noninflammatory conditions, inflammation, contributes loss stability.