title: FOXC2 controls Ang-2 expression and modulates angiogenesis, vascular patterning, remodeling, and functions in adipose tissue.
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.
authors.affiliation: Department of Microbiology, Laboratory of Angiogenesis Research, Tumor and Cell Biology, Karolinska Institute, Stockholm, Sweden.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Xue
authors.forename: Renhai
authors.initials: R
authors.lastname: Cao
authors.forename: Daniel
authors.initials: D
authors.lastname: Nilsson
authors.forename: Shaohua
authors.initials: S
authors.lastname: Chen
authors.forename: Rickard
authors.initials: R
authors.lastname: Westergren
authors.forename: Eva-Maria
authors.initials: EM
authors.lastname: Hedlund
authors.forename: Cecile
authors.initials: C
authors.lastname: Martijn
authors.forename: Lena
authors.initials: L
authors.lastname: Rondahl
authors.forename: Per
authors.initials: P
authors.lastname: Krauli
authors.forename: Erik
authors.initials: E
authors.lastname: Walum
authors.forename: Sven
authors.initials: S
authors.lastname: Enerbäck
authors.forename: Yihai
authors.initials: Y
authors.lastname: Cao
mesh_terms: D017667:Adipocytes / Q000378:metabolism; D050156:Adipogenesis / Q000235:genetics / Q000502:physiology; D000273:Adipose Tissue / Q000098:blood supply* / Q000502:physiology*; D002001:Adipose Tissue, Brown / Q000098:blood supply / Q000502:physiology; D042702:Angiopoietin-2 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000502:physiology; D000818:Animals; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000502:physiology*; D005786:Gene Expression Regulation; D051379:Mice; D008822:Mice, Transgenic; D018919:Neovascularization, Physiologic / Q000235:genetics; D010641:Phenotype; D011401:Promoter Regions, Genetic; D015398:Signal Transduction
chemical_list: D042702:Angiopoietin-2; D051858:Forkhead Transcription Factors; C082078:mesenchyme fork head 1 protein