title: Adipose tissue endothelial cells from obese human subjects: differences among depots in angiogenic, metabolic, and inflammatory gene expression and cellular senescence.
abstract: OBJECTIVE
  Regional differences among adipose depots in capacities for fatty acid storage, susceptibility to hypoxia, and inflammation likely contribute to complications of obesity. We defined the properties of endothelial cells (EC) isolated from subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) biopsied in parallel from obese subjects.
  
  
  METHODS
  The architecture and properties of the fat tissue capillary network were analyzed using immunohistochemistry and flow cytometry. CD34(+)/CD31(+) EC were isolated by immunoselection/depletion. Expression of chemokines, adhesion molecules, angiogenic factor receptors, as well as lipogenic and senescence-related genes were assayed by real-time PCR. Fat cell size and expression of hypoxia-dependent genes were determined in adipocytes from both fat depots.
  
  
  RESULTS
  Hypoxia-related genes were more highly expressed in VAT than SAT adipocytes. VAT adipocytes were smaller than SAT adipocytes. Vascular density and EC abundance were higher in VAT. VAT-EC exhibited a marked angiogenic and inflammatory state with decreased expression of metabolism-related genes, including endothelial lipase, GPIHBP1, and PPAR gamma. VAT-EC had enhanced expression of the cellular senescence markers, IGFBP3 and γ-H2AX, and decreased expression of SIRT1. Exposure to VAT adipocytes caused more EC senescence-associated β-galactosidase activity than SAT adipocytes, an effect reduced in the presence of vascular endothelial growth factor A (VEGFA) neutralizing antibodies.
  
  
  CONCLUSIONS
  VAT-EC exhibit a more marked angiogenic and proinflammatory state than SAT-EC. This phenotype may be related to premature EC senescence. VAT-EC may contribute to hypoxia and inflammation in VAT.
authors: Institut National de la Santé et de la Recherche Médicale, U858, Institut de Médecine Moléculaire de Rangueil, Toulouse, France.
authors: Aurélie
authors: A
authors: Villaret
authors: Jean
authors: J
authors: Galitzky
authors: Pauline
authors: P
authors: Decaunes
authors: David
authors: D
authors: Estève
authors: Marie-Adeline
authors: MA
authors: Marques
authors: Coralie
authors: C
authors: Sengenès
authors: Patrick
authors: P
authors: Chiotasso
authors: Tamara
authors: T
authors: Tchkonia
authors: Max
authors: M
authors: Lafontan
authors: James L
authors: JL
authors: Kirkland
authors: Anne
authors: A
authors: Bouloumié
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D000273:Adipose Tissue / Q000378:metabolism* / Q000473:pathology*; D000328:Adult; D001706:Biopsy; D015992:Body Mass Index; D016922:Cellular Senescence / Q000502:physiology*; D054418:Chemokine CCL20 / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D006937:Hypercholesterolemia / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006973:Hypertension / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry / Q000379:methods; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D050152:Intra-Abdominal Fat / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D012016:Reference Values; D050151:Subcutaneous Fat / Q000378:metabolism / Q000473:pathology
chemical_list: D054418:Chemokine CCL20