Published online before print June 16, 2005, doi: 10.1161/01.RES.0000174093.64855.a6
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Submitted on March 29, 2005
Revised on June 8, 2005
Accepted on June 8, 2005
Long-Term and Sustained COMP-Ang1 Induces Long-Lasting Vascular Enlargement and Enhanced Blood Flow
Chung-Hyun Cho ;
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.
* To whom correspondence should be addressed. 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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