Cited by 112Angiogenesis and VEGF in CancerAdipose Tissue and MetabolismAdipokines, Inflammation, and Metabolic Diseases

FOXC2 controls Ang-2 expression and modulates angiogenesis, vascular patterning, remodeling, and functions in adipose tissue

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Xue, Yuan, Cao, Renhai, Nilsson, Daniel, Chen, Shaohua, Westergren, Rickard, Hedlund, Eva-Maria, Martijn, Cecile, Rondahl, Lena +4 more·2008·Proceedings of the National Academy of Sciences

Abstract

Adipogenesis is spatiotemporally coupled to angiogenesis throughout adult life, and the interplay between these two processes is communicated by multiple factors. Here we show that in a transgenic mouse model, increased expression of forkhead box C2 (FOXC2) in the adipose tissue affects angiogenesis, vascular patterning, and functions. White and brown adipose tissues contain a considerably high density of microvessels appearing as vascular plexuses, which show redistribution of vascular smooth muscle cells and pericytes. Dysfunction of these primitive vessels is reflected by impairment of skin wound healing. We further provide a mechanistic insight of the vascular phenotype by showing that FOXC2 controls Ang-2 expression by direct activation of its promoter in adipocytes. Remarkably, an Ang-2-specific antagonist almost completely reverses this vascular phenotype. Thus, the FOXC2–Ang-2 signaling system is crucial for controlling adipose vascular function, which is part of an adaptation to increased adipose tissue metabolism.

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Crossref · 10.1073/pnas.0802486105

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  • Ang-2 is an established transcriptional target of FOXC2.

    “Given that Ang-2 is an established transcriptional target of FOXC2 (90)”

    From Adipose tissue remodeling and obesity (2011) · cites this paper as [90]

  • Xue and colleagues reported that AT FOXC2 can mediate certain aspects of angiogenesis and vascular patterning.

    “Xue and colleagues recently reported that AT FOXC2 can mediate certain aspects of angiogenesis and vascular patterning (90)”

    From Adipose tissue remodeling and obesity (2011) · cites this paper as [90]

  • When inhibiting the function of Ang-2 with a neutralizing antibody, the effects caused by FOXC2 are equally blocked.

    “When inhibiting the function of Ang-2 with a neutralizing antibody, the effects caused by FOXC2 are equally blocked (90)”

    From Adipose tissue remodeling and obesity (2011) · cites this paper as [90]

  • It is likely that Ang-2 plays an important role in FOXC2-mediated angiogenesis and vascular patterning in AT.

    “it is likely that Ang-2 plays an important role in this pathway”

    From Adipose tissue remodeling and obesity (2011) · cites this paper as [90]

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Authors
Xue, Y., Cao, R., Nilsson, D., Chen, S., Westergren, R., Hedlund, E.-M., Martijn, C., Rondahl, L., Krauli, P., Walum, E., Enerbäck, S., & Cao, Y.
Affiliations
  • Karolinska Institutet (SE)
  • University of Gothenburg (SE)
  • Biovitrum AB, Strandbergsgatan 49, P12-4, SE-112 76 Stockholm, Sweden
  • University of Toronto (CA)
  • Swedish Orphan Biovitrum (Sweden) (SE)
Corresponding author
Cao, Yihai
Venue
Proceedings of the National Academy of Sciences
Published
2008-07-22
Volume
105
Issue
29
Pages
10167-10172
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W1966561876
Cited by
112
References
55
Citations by year
2026: 2 · 2025: 8 · 2024: 3 · 2023: 2 · 2022: 6 · 2021: 4 · 2020: 4 · 2019: 6 · 2018: 3 · 2017: 5 · 2016: 3 · 2015: 6 · 2014: 8 · 2013: 14 · 2012: 10
FWCI
3.84
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Amgen
  • Swedish Cancer Foundation
  • European Commission
  • Stiftelsen för Strategisk Forskning
  • Karolinska Institutet
  • Vetenskapsrådet
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
  • Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
Keywords
FOXC2, angiopoietin-2, adipose tissue angiogenesis, vascular patterning, vascular remodeling, vascular smooth muscle cells, pericytes, wound healing, adipocytes, promoter activation, white adipose tissue, brown adipose tissue, adipose tissue metabolism
MeSH terms
Adipose Tissue, Animals, Adipose Tissue, Brown, Gene Expression Regulation, Mice, Transgenic, Phenotype, Promoter Regions, Genetic, Signal Transduction, Adipocytes, Neovascularization, Physiologic, Angiopoietin-2, Adipogenesis, Mice, Forkhead Transcription Factors

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