In vivo actions of angiopoietins on quiescent and remodeling blood and lymphatic vessels in mouse airways and skin.
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.


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.


CONCLUSIONS
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.
Kim
Kyung Eun
KE
National Research Laboratory of Vascular Biology and Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Korea.
Cho
Chung-Hyun
CH
Kim
Hak-Zoo
HZ
Baluk
Peter
P
McDonald
Donald M
DM
Koh
Gou Young
GY
D042682:Angiopoietins / Q000494:pharmacology*; D000818:Animals; D001808:Blood Vessels / Q000187:drug effects* / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D042583:Lymphangiogenesis / Q000187:drug effects*; D042601:Lymphatic Vessels / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000502:physiology; D011336:Probability; D042787:Receptor, TIE-2 / Q000187:drug effects* / Q000378:metabolism; D012038:Regeneration / Q000187:drug effects; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D012680:Sensitivity and Specificity; D012867:Skin / Q000098:blood supply / Q000187:drug effects; D014132:Trachea / Q000098:blood supply / Q000187:drug effects
D042682:Angiopoietins; D042787:Receptor, TIE-2