title: Angiogenic role of LYVE-1-positive macrophages in adipose tissue.
abstract: 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.
authors.affiliation: National Research Laboratory of Vascular Biology and Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Korea.
authors.forename: Chung-Hyun
authors.initials: CH
authors.lastname: Cho
authors.forename: Young Jun
authors.initials: YJ
authors.lastname: Koh
authors.forename: Jinah
authors.initials: J
authors.lastname: Han
authors.forename: Hoon-Ki
authors.initials: HK
authors.lastname: Sung
authors.forename: Hyuek
authors.initials: H
authors.lastname: Jong Lee
authors.forename: Tohru
authors.initials: T
authors.lastname: Morisada
authors.forename: Reto A
authors.initials: RA
authors.lastname: Schwendener
authors.forename: Rolf A
authors.initials: RA
authors.lastname: Brekken
authors.forename: Guson
authors.initials: G
authors.lastname: Kang
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Oike
authors.forename: Tae-Saeng
authors.initials: TS
authors.lastname: Choi
authors.forename: Toshio
authors.initials: T
authors.lastname: Suda
authors.forename: Ook-Joon
authors.initials: OJ
authors.lastname: Yoo
authors.forename: Gou Young
authors.initials: GY
authors.lastname: Koh
mesh_terms: D050156:Adipogenesis / Q000502:physiology; D000273:Adipose Tissue / Q000098:blood supply / Q000254:growth & development / Q000502:physiology*; D000818:Animals; D002465:Cell Movement / Q000502:physiology; D004822:Epididymis / Q000098:blood supply / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D006023:Glycoproteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D008264:Macrophages / Q000166:cytology / Q000502:physiology*; D008297:Male; D026901:Membrane Transport Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018919:Neovascularization, Physiologic / Q000502:physiology*
chemical_list: D006023:Glycoproteins; D026901:Membrane Transport Proteins; C492273:LYVE1 protein, mouse