title: Change of walking distance in intermittent claudication: impact on inflammation, oxidative stress and mononuclear cells: a pilot study.
abstract: BACKGROUND
  Atherosclerosis is a chronic inflammatory process involving the immune system and formation of reactive oxygen species (ROS). We investigated changes of mononuclear blood cells and ROS production in relation to the walking distance of patients with intermittent claudication during home-based exercise training.
  
  
  METHODS
  Forty patients with intermittent claudication were asked to perform a home-based exercise training for a mean time of 12 months. ROS formation was measured using the luminol analogue L-012. Peripheral blood leucocytes [monocytes, polymorphonuclear neutrophils (PMN) and dendritic cells (DC)] were analysed by flow cytometry and analysed for the expression of major inflammatory surface molecules.
  
  
  RESULTS
  At follow-up, patients showed an increased walking distance and reduced ROS production upon stimulation with a phorbol ester derivative (PDBu) (p < 0.01). Monocytes changed their inflammatory phenotype towards an increased anti-inflammatory CD14(++)CD16(-) subpopulation (p < 0.0001). Adhesion molecules CD11b, CD11c and TREM-1 on monocytes and PMN decreased (all p < 0.01). On DC expression of HLA-DR, CD86 or CD40 decreased at follow-up. Inflammatory markers like fibrinogen, C-reactive protein or soluble TREM-1 (sTREM-1) decreased over the observation period. Finally, we found a close relation of sTREM-1 with the walking distance, fibrinogen and ROS production.
  
  
  CONCLUSIONS
  We observed an amelioration of the proinflammatory phenotype on monocytes, DC and PMN, as well as a reduced ROS production in PAD patients under home-based exercise, paralleled by an increased walking distance. Our data suggest that a reduced inflammatory state might be achieved by regular walking exercise, possibly in a dimension proportionately to changes in walking distance.
authors.affiliation: Department of Internal Medicine II, University Medical Center of the Johannes Gutenberg-University Mainz, Langenbeckstr. 1, 55131, Mainz, Germany, dopheide@uni-mainz.de.
authors.forename: Jörn F
authors.initials: JF
authors.lastname: Dopheide
authors.forename: Martin
authors.initials: M
authors.lastname: Scheer
authors.forename: Christopher
authors.initials: C
authors.lastname: Doppler
authors.forename: Viviane
authors.initials: V
authors.lastname: Obst
authors.forename: Pamela
authors.initials: P
authors.lastname: Stein
authors.forename: Markus
authors.initials: M
authors.lastname: Vosseler
authors.forename: Nico
authors.initials: N
authors.lastname: Abegunewardene
authors.forename: Tommaso
authors.initials: T
authors.lastname: Gori
authors.forename: Thomas
authors.initials: T
authors.lastname: Münzel
authors.forename: Andreas
authors.initials: A
authors.lastname: Daiber
authors.forename: Markus P
authors.initials: MP
authors.lastname: Radsak
authors.forename: Christine
authors.initials: C
authors.lastname: Espinola-Klein
mesh_terms: D015415:Biomarkers / Q000097:blood; D015815:Cell Adhesion Molecules / Q000097:blood; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D005080:Exercise Test; D005081:Exercise Therapy; D017079:Exercise Tolerance; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D007383:Intermittent Claudication / Q000097:blood / Q000175:diagnosis / Q000276:immunology / Q000503:physiopathology / Q000628:therapy*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism*; D008297:Male; D018384:Oxidative Stress; D058729:Peripheral Arterial Disease / Q000097:blood / Q000175:diagnosis / Q000276:immunology / Q000503:physiopathology / Q000628:therapy*; D010641:Phenotype; D010865:Pilot Projects; D017382:Reactive Oxygen Species / Q000097:blood; D020127:Recovery of Function; D013997:Time Factors; D016896:Treatment Outcome; D016138:Walking
chemical_list: D015415:Biomarkers; D015815:Cell Adhesion Molecules; D018836:Inflammation Mediators; D017382:Reactive Oxygen Species