Angiogenic Role of LYVE-1–Positive Macrophages in Adipose Tissue
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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.
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Hypoxic regions at the tip of the mouse epididymal fat pad promote infiltration of macrophages expressing LYVE-1.
“The hypoxic regions at the tip of the mouse epididymal fat pad have been shown to promote infiltration of a specific species of macrophage expressing the lymphatic endothelial marker LYVE-1.”
From The ominous triad of adipose tissue dysfunction: inflammation, fibrosis, and impaired angiogenesis. (2017) · cites this paper as [52]
The new vasculature provides a framework for adipogenesis and growth of the fat pad.
“This new vasculature provides the framework for adipogenesis and growth of the fat pad (52).”
From The ominous triad of adipose tissue dysfunction: inflammation, fibrosis, and impaired angiogenesis. (2017) · cites this paper as [52]
LYVE-1+ macrophages promote angiogenesis by secreting MMP-9, -12, and -7 to remodel ECM and angiogenic factors such as VEGF to stimulate a dense vascular network.
“These LYVE-1 + macrophages promote angiogenesis through secretion of MMP-9, -12, and -7 to remodel the ECM and angiogenic factors like VEGF to stimulate the growth of a dense vascular network.”
From The ominous triad of adipose tissue dysfunction: inflammation, fibrosis, and impaired angiogenesis. (2017) · cites this paper as [52]
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- Authors
- Cho, C.-H., Jun Koh, Y., Han, J., Sung, H.-K., Jong Lee, H., Morisada, T., Schwendener, R. A., Brekken, R. A., Kang, G., Oike, Y., Choi, T.-S., Suda, T., Yoo, O.-J., & Koh, G. Y.
- Affiliations
- Korea Advanced Institute of Science and Technology (KR)
- 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...
- ORCID
- Venue
- Circulation Research
- Published
- 2007-03-02
- Volume
- 100
- Issue
- 4
- Pages
- e47-57
- ISSN
- 0009-7330 (ISSN-L)
- 1524-4571
- OpenAlex
- W2150586369
- Cited by
- 309
- References
- 64
- Citations by year
- 2026: 8 · 2025: 14 · 2024: 30 · 2023: 13 · 2022: 19 · 2021: 19 · 2020: 13 · 2019: 12 · 2018: 19 · 2017: 7 · 2016: 12 · 2015: 10 · 2014: 14 · 2013: 27 · 2012: 14
- FWCI
- 7.81
- Type
- journal article
- Language
- en
- Open access
- green
- www.zora.uzh.ch
- Licence
- other-oa
- Locations
- Circulation Research (publishedVersion)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- Korea Advanced Institute of Science and Technology
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
- Keywords
- adipose tissue angiogenesis, epididymal adipose tissue, adipogenesis, macrophage recruitment, CXCL12, VEGF/VEGFR2 signaling, matrix metalloproteinases, hypoxia, bone marrow-derived macrophages
- MeSH terms
- Adipose Tissue, Animals, Cell Movement, Epididymis, Glycoproteins, Macrophages, Male, Mice, Inbred C57BL, Mice, Knockout, Gene Expression Regulation, Developmental, Neovascularization, Physiologic, Membrane Transport Proteins, Adipogenesis, Mice
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