title: Effects of obesity and weight loss on the functional properties of early outgrowth endothelial progenitor cells.
abstract: OBJECTIVE
  The purpose of this study was to examine the impact of obesity and weight loss on the angiogenic and regenerative capacity of endothelial progenitor cells (EPCs).
  
  
  BACKGROUND
  EPCs participate in angiogenesis and tissue repair. Several cardiovascular risk factors are associated with EPC dysfunction.
  
  
  METHODS
  Early outgrowth EPCs were isolated from 49 obese (age 42 +/- 14 years; body mass index 42 +/- 7 kg/m(2)) normoglycemic participants in a professional weight reduction program and compared with those from 49 age-matched lean controls. EPC function was tested both in vitro and in vivo.
  
  
  RESULTS
  EPCs expanded from the obese possessed reduced adhesive, migratory, and angiogenic capacity, and mice treated with obese EPCs exhibited reduced EPC homing in ischemic hind limbs in vivo. EPCs from the obese subjects failed to respond to conditioned medium of lean controls or to potent angiogenic factors such as vascular endothelial growth factor. Although no differences existed between lean and obese EPCs regarding the surface expression of vascular endothelial growth factor or chemokine receptors, basal p38 mitogen-activated protein kinase (MAPK) phosphorylation was elevated in obese EPCs (3.7 +/- 2.1-fold increase; p = 0.006). These cells also showed reduced secretion of the angiogenic chemokines interleukin-8 (p = 0.047) and monocyte chemoattractant protein-1 (p = 0.012). By inhibiting p38 MAPK, we could restore chemokine levels to those of lean control EPCs and also improve the angiogenic properties of obese EPCs. Accordingly, 6-month follow-up of 26 obese persons who achieved significant weight reduction revealed normalization of p38 MAPK phosphorylation levels and improved EPC function.
  
  
  CONCLUSIONS
  Obesity is associated with a reversible functional impairment of EPCs. This involves reduced secretion of angiogenic chemokines and increased basal phosphorylation of signaling molecules, notably p38 MAPK.
authors.affiliation: Department of Cardiology and Pulmonology, University of Göttingen, Göttingen, Germany.
authors.forename: Nana-Maria
authors.initials: NM
authors.lastname: Heida
authors.forename: Jan-Peter
authors.initials: JP
authors.lastname: Müller
authors.forename: I-Fen
authors.initials: IF
authors.lastname: Cheng
authors.forename: Maren
authors.initials: M
authors.lastname: Leifheit-Nestler
authors.forename: Vivien
authors.initials: V
authors.lastname: Faustin
authors.forename: Joachim
authors.initials: J
authors.lastname: Riggert
authors.forename: Gerd
authors.initials: G
authors.lastname: Hasenfuss
authors.forename: Stavros
authors.initials: S
authors.lastname: Konstantinides
authors.forename: Katrin
authors.initials: K
authors.lastname: Schäfer
mesh_terms: D000328:Adult; D042783:Endothelial Cells / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D018919:Neovascularization, Physiologic / Q000502:physiology*; D009765:Obesity / Q000503:physiopathology*; D012038:Regeneration / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D013234:Stem Cells / Q000502:physiology*; D015431:Weight Loss / Q000502:physiology*