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Biotech / Medical : Regeneron Pharmaceuticals -- Ignore unavailable to you. Want to Upgrade?

To: Miljenko Zuanic who wrote (720)	12/3/2002 8:44:18 PM
From: Miljenko Zuanic	Read Replies (1) \| Respond to of 3559

jci.org J. Clin. Invest. 110:1619-1628 (2002). doi:10.1172/JCI200215621. Copyright ©2002 by the American Society for Clinical Investigation -------------------------------------------------------------------------------- Article Recombinant angiopoietin-1 restores higher-order architecture of growing blood vessels in mice in the absence of mural cells Akiyoshi Uemura1,2, Minetaro Ogawa1, Masanori Hirashima1, Takashi Fujiwara3, Shinji Koyama2, Hitoshi Takagi2, Yoshihito Honda2, Stanley J. Wiegand4, George D. Yancopoulos4 and Shin-Ichi Nishikawa1,5 1 Department of Molecular Genetics, and 2 Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan 3 Laboratory Animal Center, Ehime University School of Medicine, Ehime, Japan 4 Regeneron Pharmaceuticals Inc., Tarrytown, New York, USA 5 Stem Cell Research Group, RIKEN Center for Developmental Biology, Kobe, Japan Address correspondence to: Akiyoshi Uemura, Department of Molecular Genetics, Kyoto University Graduate School of Medicine, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507 Japan. Phone: 81-75-751-4162; Fax: 81-75-751-4169; E-mail: auemura@kuhp.kyoto-u.ac.jp. Received for publication April 5, 2002, and accepted in revised form September 24, 2002. Interactions between endothelial cells (ECs) and perivascular mural cells (MCs) via signaling molecules or physical contacts are implicated both in vascular remodeling and maintenance of vascular integrity. However, it remains unclear how MCs regulate the morphogenic activity of ECs to form an organized vascular architecture, comprising distinct artery, vein, and capillary, from a simple mesh-like network. A clear elucidation of this question requires an experimental model system in which ECs are separated from MCs and yet form vascular structures. Here we report that injection of an antagonistic mAb against PDGFR-ß into murine neonates provides such an experimental system in the retina by completely blocking MC recruitment to developing vessels. While a vascular network was formed even in the absence of MCs, it was poorly remodeled and leaky. Using this vascular system ideal for direct assessment of the activities of MC-derived molecules, we show that addition of recombinant modified angiopoietin-1 restored a hierarchical vasculature, and also rescued retinal edema and hemorrhage in the complete absence of MCs. These observations demonstrate the potential of Ang1 as a new therapeutic modality for MC dropout in diseases such as diabetic retinopathies.