title: Chronic heart failure and aging - effects of exercise training on endothelial function and mechanisms of endothelial regeneration: Results from the Leipzig Exercise Intervention in Chronic heart failure and Aging (LEICA) study.
abstract: BACKGROUND
  A reduction in number and function of endothelial progenitor cells (EPCs) occurs in both physiologic aging and chronic heart failure (CHF). We assessed whether disease and aging have additive effects on EPCs or whether beneficial effects of exercise training are diminished in old age.
  
  
  METHODS
  We randomized 60 patients with stable CHF and 60 referent controls to a training or a control group. To detect possible aging effects we included subjects below 55 (young) and above 65 years (older). Subjects in the training group exercised four times daily at 60% to 70% of VO2max for four weeks under supervision. At baseline and after the intervention the number and function of EPCs were assessed.
  
  
  RESULTS
  As compared with young referent controls, older referent controls showed at baseline a reduced EPC number (young: 190 ± 37 CD34/KDR positive cells/ml blood; older: 131 ± 26 CD34/KDR positive cells/ml blood; p < 0.05) and function (young: 230 ± 41 migrated cells/1000 plated cells; older: 185 ± 28 cells/1000 plated cells; p < 0.05). In young and older CHF patients EPC-number (young: 85 ± 21 CD34/KDR positive cells/ml blood; older: 78 ± 20 CD34/KDR positive cells/ml blood) and EPC-function (young: 113 ± 26 cells/1000 plated cells; older: 120 ± 27 cells/1000 plated cells) were impaired. As a result of exercise training, EPC function improved by 24% in older referent controls (p < 0.05), while it remained unchanged in young training referent controls and controls respectively. In young and older patients with CHF four weeks of exercise training resulted in a significant improvement in EPC numbers and EPC function (young: number +66% function +43%; p < 0.05; older: number +69% function +36%; p < 0.05). These results were accompanied by a significant increase in flow mediated dilatation in the training groups of young/older CHF patients and in older referent controls.
  
  
  CONCLUSIONS
  Four weeks of exercise training are effective in improving EPC number and EPC function in CHF patients. These training effects were not impaired among older patients, emphasizing the potentials of rehabilitation interventions in a patient group where CHF has a high prevalence.
authors.affiliation: University of Leipzig, Heart Centre, Department of Internal Medicine/Cardiology, Germany marcus.sandri@medizin.uni-leipzig.de.
authors.forename: Marcus
authors.initials: M
authors.lastname: Sandri
authors.affiliation: University of Leipzig, Heart Centre, Department of Internal Medicine/Cardiology, Germany.
authors.forename: Manuel
authors.initials: M
authors.lastname: Viehmann
authors.affiliation: University of Leipzig, Heart Centre, Department of Internal Medicine/Cardiology, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Adams
authors.affiliation: University of Leipzig, Heart Centre, Department of Internal Medicine/Cardiology, Germany.
authors.forename: Kristin
authors.initials: K
authors.lastname: Rabald
authors.affiliation: University of Leipzig, Heart Centre, Department of Internal Medicine/Cardiology, Germany.
authors.forename: Norman
authors.initials: N
authors.lastname: Mangner
authors.affiliation: University of Leipzig, Heart Centre, Department of Internal Medicine/Cardiology, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Höllriegel
authors.affiliation: University of Leipzig, Heart Centre, Department of Internal Medicine/Cardiology, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Lurz
authors.affiliation: University of Leipzig, Heart Centre, Department of Internal Medicine/Cardiology, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Erbs
authors.affiliation: University of Leipzig, Heart Centre, Department of Internal Medicine/Cardiology, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Linke
authors.affiliation: University of Leipzig, Heart Centre, Department of Internal Medicine/Cardiology, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Kirsch
authors.affiliation: Klinikum Weißenfels, Department of Cardiology and Angiology, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Möbius-Winkler
authors.affiliation: University of Leipzig, Institute for Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Thiery
authors.affiliation: University of Leipzig, Institute for Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Teupser
authors.affiliation: Klinikum Links der Weser, Department of Cardiology and Angiology, Bremen, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Hambrecht
authors.affiliation: Martin-Luther-University Halle/Wittenberg, University Hospital, Department of Internal Medicine III, Halle/Saale, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Schuler
authors.affiliation: Martin-Luther-University Halle/Wittenberg, University Hospital, Department of Internal Medicine III, Halle/Saale, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Gielen
mesh_terms: D000368:Aged; D000375:Aging / Q000502:physiology; D001120:Arginine / Q000031:analogs & derivatives / Q000097:blood; D001783:Blood Flow Velocity; D002452:Cell Count; D054377:Chemokine CXCL12 / Q000097:blood; D066026:Endothelial Progenitor Cells / Q000166:cytology / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology*; D005081:Exercise Therapy; D006333:Heart Failure / Q000097:blood / Q000503:physiopathology / Q000534:rehabilitation*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D008875:Middle Aged; D011446:Prospective Studies; D017534:Radial Artery / Q000000981:diagnostic imaging; D012038:Regeneration; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood; D042461:Vascular Endothelial Growth Factor A
chemical_list: C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019010:Vascular Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A; D018799:Intercellular Adhesion Molecule-1; C018524:N,N-dimethylarginine; D001120:Arginine
keywords: Heart failure; aging; endothelial progenitor cells; exercise; regeneration; vascular endothelial growth factors