Angiopoietin-2, a Natural Antagonist for Tie2 That Disrupts in vivo Angiogenesis

TLDR

Angiogenesis requires a precise balance of positive and negative signals, with Ang1 promoting vessel growth through Tie2 while Ang2 acts as a natural antagonist, underscoring the need for tight regulation of this receptor system. Ang2 was identified as a natural antagonist of Ang1/Tie2, and its transgenic overexpression in mice disrupts embryonic blood vessel formation.

Abstract

Angiogenesis is thought to depend on a precise balance of positive and negative regulation. Angiopoietin-1 (Ang1) is an angiogenic factor that signals through the endothelial cell–specific Tie2 receptor tyrosine kinase. Like vascular endothelial growth factor, Ang1 is essential for normal vascular development in the mouse. An Ang1 relative, termed angiopoietin-2 (Ang2), was identified by homology screening and shown to be a naturally occurring antagonist for Ang1 and Tie2. Transgenic overexpression of Ang2 disrupts blood vessel formation in the mouse embryo. In adult mice and humans, Ang2 is expressed only at sites of vascular remodeling. Natural antagonists for vertebrate receptor tyrosine kinases are atypical; thus, the discovery of a negative regulator acting on Tie2 emphasizes the need for exquisite regulation of this angiogenic receptor system.