title: Exercise training increases endothelial progenitor cells and decreases asymmetric dimethylarginine in peripheral arterial disease: a randomized controlled trial.
abstract: BACKGROUND
  Supervised exercise training (SET) is recommended as initial treatment to improve walking capacity in peripheral arterial disease (PAD) patients with intermittent claudication. Various mechanisms by which SET yields beneficial effects are postulated, however data regarding its influence on angiogenesis are scarce. Thus, we designed a prospective randomized controlled trial to study the impact of SET on markers of angiogenesis and endothelial function in PAD.
  
  
  METHODS
  Forty PAD patients were randomized to SET on top of best medical treatment (SET+BMT) for 6 months versus best medical treatment (BMT) only. Endothelial progenitor cells (EPC) were assessed by whole-blood flow cytometry (co-expression of CD34+ CD133+ KDR+) and cell culture assays (endothelial cell-colony forming units, circulating angiogenic cells, migration assay) at baseline, 3, 6 and 12-months after inclusion. Changes of plasma levels of asymmetric dimethylarginine (ADMA), vascular endothelial growth factor (VEGF), stromal cell-derived factor-1 (SDF-1) and maximum walking distance were determined.
  
  
  RESULTS
  EPC - measured by flow cytometric and cell culture techniques - increased significantly upon training paralleled by a significant decrease of ADMA when compared to the BMT group (p<0.05). Six months after training cessation, the beneficial effect of SET on EPC diminished, but maximum walking distance was significantly improved compared to baseline and controls (p<0.05). No significant changes were observed for VEGF and SDF-1 plasma levels in time course.
  
  
  CONCLUSIONS
  SET increases circulating EPC counts and decreases ADMA levels reflecting enhanced angiogenesis and improved endothelial function, which might contribute to cardiovascular risk reduction.
authors.affiliation: Department of Internal Medicine II, Division of Angiology, Medical University Vienna, Vienna, Austria.
authors.forename: Oliver
authors.initials: O
authors.lastname: Schlager
authors.forename: Aura
authors.initials: A
authors.lastname: Giurgea
authors.forename: Othmar
authors.initials: O
authors.lastname: Schuhfried
authors.forename: Daniela
authors.initials: D
authors.lastname: Seidinger
authors.forename: Alexandra
authors.initials: A
authors.lastname: Hammer
authors.forename: Marion
authors.initials: M
authors.lastname: Gröger
authors.forename: Veronika
authors.initials: V
authors.lastname: Fialka-Moser
authors.forename: Michael
authors.initials: M
authors.lastname: Gschwandtner
authors.forename: Renate
authors.initials: R
authors.lastname: Koppensteiner
authors.forename: Sabine
authors.initials: S
authors.lastname: Steiner
mesh_terms: D000368:Aged; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D002465:Cell Movement; D054377:Chemokine CXCL12 / Q000097:blood; D042783:Endothelial Cells / Q000166:cytology*; D015444:Exercise; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D007383:Intermittent Claudication / Q000175:diagnosis / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D058729:Peripheral Arterial Disease / Q000097:blood* / Q000628:therapy*; D013234:Stem Cells / Q000166:cytology*; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D054377:Chemokine CXCL12; D042461:Vascular Endothelial Growth Factor A; C018524:N,N-dimethylarginine; D001120:Arginine