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(Circulation Research. 2005;97:86.)
© 2005 American Heart Association, Inc.

Integrative Physiology

Long-Term and Sustained COMP-Ang1 Induces Long-Lasting Vascular Enlargement and Enhanced Blood Flow

Chung-Hyun Cho, Kyung Eun Kim, Jonghoe Byun, Hyung-Suk Jang, Duk-Kyung Kim, Peter Baluk, Fabienne Baffert, Gyun Min Lee, Naoki Mochizuki, Jin Kim, Byeong Hwa Jeon, Donald M. McDonald, Gou Young Koh

From the Biomedical Research Center and Department of Biological Sciences (C.-H.C., K.E.K., G.M.L., G.Y.K), Korea Advanced Institute of Science and Technology, Daejeon, Korea; the Department of Medicine (J.B., H.-S.J., D.-K.K.), Samsung Medical Center and Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, Korea; the Cardiovascular Research Institute, Comprehensive Cancer Center, and Department of Anatomy (P.B., F.B., D.M.M.), University of California, San Francisco; the Department of Structural Analysis (N.M.), National Cardiovascular Center Research Institute, Suita, Osaka, Japan; the Department of Anatomy (J.K.), College of Medicine, The Catholic University of Korea Seoul; and the Department of Physiology (B.H.J), College of Medicine, Chungnam National University Daejeon, Korea.

Correspondence to Gou Young Koh, Biomedical Research Center, Korea Advanced Institute of Science and Technology, 373-1, Guseong-dong, Daejeon, 305-701, Republic of Korea. E-mail gykoh{at}kaist.ac.kr

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.

Key Words: angiopoietin-1 • COMP-Ang1 • vascular enlargement • blood flow

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