Published online before print February 1, 2007, doi: 10.1161/01.RES.0000259564.92792.93
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Submitted on October 10, 2006
Revised on January 16, 2007
Accepted on January 23, 2007
Angiogenic Role of LYVE-1-positive Macrophages in Adipose Tissue
Chung-Hyun Cho ;
From the National Research Laboratory of Vascular Biology and Department of Biological Sciences (C-H.C., Y.J.K., J.H., H-K. S., H.J.L., O-J.Y., G.Y.K.), Korea Advanced Institute of Science and Technology, Daejeon, Korea; Department of Cell Differentiation (T.M.,Y.O., T.S.), The Sakaguchi Laboratory, Keio University Internal Medicine, Tokyo, Japan; Laboratory of Liposome Research (R.A.S.), Institute of Molecular Cancer Research, University of Zurich, Switzerland; Departments of Surgery and Pharmacology (R.A.B), Hamon Center for Therapeutic Oncology Research, UT-Southwestern Medical Center, Dallas, Tex; Department of Biochemistry and Biophysics (G.K.), University of California, San Francisco; Department of Microbiology (T-S.C), College of Medicine, Dankook University, Chonan, Korea.
* To whom correspondence should be addressed. E-mail: gykoh{at}kaist.ac.kr.
Here we report the discovery of a characteristic dense vascular network (DVN) in the tip portion of epididymal adipose tissue in adult mice. The DVN is formed by angiogenesis rather than by vasculogenesis, and has functional blood circulation. This DVN and its subsequent branching may provide a new functional route for adipogenesis. The recruitment, infiltration, and accumulation of bone marrow-derived LYVE-1+ macrophages in the tip region are crucial for the formation of the DVN. Matrix metalloproteinases (MMPs) and the VEGF-VEGFR2 system are responsible not only for the formation of the DVN, but also for the recruitment and infiltration of LYVE-1+ macrophages into the epididymal adipose tissue tip region. SDF-1, but not the MCP-1-CCR2 system, is a critical factor in recruitment and ongoing retention of macrophages in this area. We also demonstrate that the tip region of epididymal adipose tissue is highly hypoxic, and thus provides a microenvironment conducive to the high expression and enhanced activities of VEGF, VEGFR2, MMPs, and SDF-1 in autocrine and paracrine manners, to create an ideal niche for the recruitment, retention, and angiogenic action of macrophages. These findings shed light on the complex interplay between macrophage infiltration, angiogenesis, and adipogenesis in the tip region of adult epididymal adipose tissue, and provide novel insight into the regulation of alternative outgrowth of adipose tissue.
Key words: adipogenesis • angiogenesis • endothelial cell differentiation • endothelial cell growth • lymphatic vessel hyaluronan receptor 1 • macrophages • matrix metalloproteinases • monocyte chemoattractant protein-1 • vascular endothelial growth factor • vascular endothelial growth factor receptors
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