Angiopoietins and angiopoietin-like proteins in angiogenesis.

Vascular network formation requires several endothelial cell growth factors. These factors have a potent angiogenic effect, and their precise coordination is essential for vascular development. Among them, angiopoietins function through the Tie2 receptor, whose signaling is critical to regulate vascular stabilization and remodeling. It has been reported that the angiopoietin/Tie2 signal is involved in survival and migration of endothelial cells and regulates vascular remodeling and maintenance of vascular integrity. More recent studies demonstrate that angiopoietin/Tie2 signaling is also required for lymphangiogenesis. The authors and several other groups have identified six angiopoietin-like proteins (Angptls) containing a coiled-coil domain and a fibrinogen-like domain, both of which are characteristic of angiopoietins. Interestingly, Angptls also function in angiogenesis through regulating survival and migration of endothelial cells, although Angptls do not bind the angiopoietin receptor Tie2. Currently, Angptls are orphan ligands, but they have been reported to have pleiotropic effects not only on vascular cells but also on metabolism and tumor biology. Here, the authors review current findings relating to the roles of angiopoietins and Angptls in vascular biology and discuss molecular mechanisms relevant to these factors and angiogenesis.