Long-term and sustained COMP-Ang1 induces long-lasting vascular enlargement and enhanced blood flow.
Vascular enlargement is a characteristic feature of angiopoietin-1 (Ang1)-induced changes in adult blood vessels. However, it is unknown whether tissues having Ang1-mediated vascular enlargement have more blood flow or whether the enlargement is reversible. We have recently created a soluble, stable and potent Ang1 variant, COMP-Ang1. In the present study, we investigated the effects of varied dose and duration of COMP-Ang1 on vascular enlargement and blood flow in the tracheal microvasculature of adult mice and explored a possible mechanism of long-lasting vascular enlargement. We found that COMP-Ang1 administered by adenoviral vector induced long-lasting vascular enlargement and increased tracheal blood flow. In contrast, short-term administration of COMP-Ang1 recombinant protein induced transient vascular enlargement that spontaneously reversed within a month. In both cases, the vascular enlargement resulted from endothelial proliferation. The COMP-Ang1-induced vascular remodeling is mediated mainly through Tie2 activation. Sustained overexpression of Tie2 could participate in the maintenance of vascular changes. Together, our findings indicate that sustained treatment with COMP-Ang1 can produce long-lasting vascular enlargement and increased blood flow.
Cho
Chung-Hyun
CH
Biomedical Research Center and Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Korea.
Kim
Kyung Eun
KE
Byun
Jonghoe
J
Jang
Hyung-Suk
HS
Kim
Duk-Kyung
DK
Baluk
Peter
P
Baffert
Fabienne
F
Lee
Gyun Min
GM
Mochizuki
Naoki
N
Kim
Jin
J
Jeon
Byeong Hwa
BH
McDonald
Donald M
DM
Koh
Gou Young
GY
D000256:Adenoviridae / Q000235:genetics; D042683:Angiopoietin-1 / Q000494:pharmacology*; D000818:Animals; D001160:Arterioles / Q000187:drug effects; D001808:Blood Vessels / Q000187:drug effects*; D016466:CHO Cells; D049109:Cell Proliferation; D006224:Cricetinae; D042783:Endothelial Cells / Q000166:cytology; D016326:Extracellular Matrix Proteins / Q000494:pharmacology*; D006023:Glycoproteins / Q000494:pharmacology*; D008297:Male; D064235:Matrilin Proteins; D051379:Mice; D008822:Mice, Transgenic; D042787:Receptor, TIE-2 / Q000502:physiology; D011994:Recombinant Proteins / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects*; D014132:Trachea / Q000098:blood supply; D014699:Venules / Q000187:drug effects
D042683:Angiopoietin-1; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; C577540:Matn1 protein, mouse; D064235:Matrilin Proteins; D011994:Recombinant Proteins; D042787:Receptor, TIE-2