Angiogenic role of LYVE-1-positive macrophages in adipose tissue.
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.
Cho
Chung-Hyun
CH
National Research Laboratory of Vascular Biology and Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Korea.
Koh
Young Jun
YJ
Han
Jinah
J
Sung
Hoon-Ki
HK
Jong Lee
Hyuek
H
Morisada
Tohru
T
Schwendener
Reto A
RA
Brekken
Rolf A
RA
Kang
Guson
G
Oike
Yuichi
Y
Choi
Tae-Saeng
TS
Suda
Toshio
T
Yoo
Ook-Joon
OJ
Koh
Gou Young
GY
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*
D006023:Glycoproteins; D026901:Membrane Transport Proteins; C492273:LYVE1 protein, mouse