Objective— We investigated and compared the in vivo effects of all four angiopoietins (COMP-Ang1, Ang2, Ang3, and Ang4) on blood and lymphatic vascular remodeling in adult mice. We analyzed the microvasculature of trachea and ear skin, and compared quiescent skin microvasculature with that during wound healing.

Methods and Results— We were able to achieve similar levels of relatively long-term and sustained circulating expression of each angiopoietin using an adenoviral delivery system. Two weeks after treatment, we observed tracheal blood and lymphatic vascular enlargement, and lymphatic filopodia formation, with the following order of potency: COMP-Ang1>Ang3=Ang4>Ang2. Co-treatment with Ang2 attenuated Ang1-induced tracheal blood and lymphatic remodeling. In the normal ear skin, all angiopoietins induced blood vessel enlargement, whereas none induced lymphatic vascular remodeling. However, in the healing margin of ear skin wounds, all angiopoietins strongly induced lymphatic vascular enlargement and formation of lymphatic sprouts and filopodia, while they potentiated blood vascular enlargement. Co-treatment of Ang2 with Ang1 produced an additive effect on these changes.

Conclusion— This study, one of the first to our knowledge to characterize the in vivo actions of all 4 angiopoietins, may expand the current concepts for use of angiopoietins for therapeutic angiogenesis and lymphangiogenesis.