title: Growth differentiation factor-15 is associated with muscle mass in chronic obstructive pulmonary disease and promotes muscle wasting in vivo.
abstract: BACKGROUND
  Loss of muscle mass is a co-morbidity common to a range of chronic diseases including chronic obstructive pulmonary disease (COPD). Several systemic features of COPD including increased inflammatory signalling, oxidative stress, and hypoxia are known to increase the expression of growth differentiation factor-15 (GDF-15), a protein associated with muscle wasting in other diseases. We therefore hypothesized that GDF-15 may contribute to muscle wasting in COPD.
  
  
  METHODS
  We determined the expression of GDF-15 in the serum and muscle of patients with COPD and analysed the association of GDF-15 expression with muscle mass and exercise performance. To determine whether GDF-15 had a direct effect on muscle, we also determined the effect of increased GDF-15 expression on the tibialis anterior of mice by electroporation.
  
  
  RESULTS
  Growth differentiation factor-15 was increased in the circulation and muscle of COPD patients compared with controls. Circulating GDF-15 was inversely correlated with rectus femoris cross-sectional area (P < 0.001) and exercise capacity (P < 0.001) in two separate cohorts of patients but was not associated with body mass index. GDF-15 levels were associated with 8-oxo-dG in the circulation of patients consistent with a role for oxidative stress in the production of this protein. Local over-expression of GDF-15 in mice caused wasting of the tibialis anterior muscle that expressed it but not in the contralateral muscle suggesting a direct effect of GDF-15 on muscle mass (P < 0.001).
  
  
  CONCLUSIONS
  Together, the data suggest that GDF-15 contributes to the loss of muscle mass in COPD.
authors.affiliation: NIHR Respiratory Biomedical Research Unit Royal Brompton & Harefield NHS Foundation Trust and Imperial College London UK.
authors.forename: Mehul S
authors.initials: MS
authors.lastname: Patel
authors.affiliation: Section of Molecular Medicine National Heart and Lung Institute, Imperial College London London UK.
authors.forename: Jen
authors.initials: J
authors.lastname: Lee
authors.affiliation: NIHR Respiratory Biomedical Research Unit Royal Brompton & Harefield NHS Foundation Trust and Imperial College London UK.
authors.forename: Manuel
authors.initials: M
authors.lastname: Baz
authors.affiliation: Institute of Infection and Immunity St George's, University of London London UK.
authors.forename: Claire E
authors.initials: CE
authors.lastname: Wells
authors.affiliation: NIHR Respiratory Biomedical Research Unit Royal Brompton & Harefield NHS Foundation Trust and Imperial College London UK.
authors.forename: Susannah
authors.initials: S
authors.lastname: Bloch
authors.affiliation: Section of Molecular Medicine National Heart and Lung Institute, Imperial College London London UK.
authors.forename: Amy
authors.initials: A
authors.lastname: Lewis
authors.affiliation: NIHR Respiratory Biomedical Research Unit Royal Brompton & Harefield NHS Foundation Trust and Imperial College London UK.
authors.forename: Anna V
authors.initials: AV
authors.lastname: Donaldson
authors.affiliation: NIHR Respiratory Biomedical Research Unit Royal Brompton & Harefield NHS Foundation Trust and Imperial College London UK.
authors.forename: Benjamin E
authors.initials: BE
authors.lastname: Garfield
authors.affiliation: NIHR Respiratory Biomedical Research Unit Royal Brompton & Harefield NHS Foundation Trust and Imperial College London UK.
authors.forename: Nicholas S
authors.initials: NS
authors.lastname: Hopkinson
authors.affiliation: NIHR Respiratory Biomedical Research Unit Royal Brompton & Harefield NHS Foundation Trust and Imperial College London UK.
authors.forename: Amanda
authors.initials: A
authors.lastname: Natanek
authors.affiliation: NIHR Respiratory Biomedical Research Unit Royal Brompton & Harefield NHS Foundation Trust and Imperial College London UK.
authors.forename: William D-C
authors.initials: WD
authors.lastname: Man
authors.affiliation: Comparative Biomedical Sciences Royal Veterinary College London UK.
authors.forename: Dominic J
authors.initials: DJ
authors.lastname: Wells
authors.affiliation: Institute of Infection and Immunity St George's, University of London London UK.
authors.forename: Emma H
authors.initials: EH
authors.lastname: Baker
authors.affiliation: NIHR Respiratory Biomedical Research Unit Royal Brompton & Harefield NHS Foundation Trust and Imperial College London UK.
authors.forename: Michael I
authors.initials: MI
authors.lastname: Polkey
authors.affiliation: Section of Molecular Medicine National Heart and Lung Institute, Imperial College London London UK.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Kemp
keywords: Atrophy; COPD; Electroporation; GDF‐15; Muscle mass