Abstract
Introduction
Klotho (KL) was discovered in transgenic rodents, mice deficient in KL develop sarcopenia and emphysema. KL is expressed both as a circulating hormone and a transmembrane protein. Limited data is available in COPD; where the quadriceps are particularly prone to dysfunction.
Aims
To assess the systemic and quadriceps expression of KL in COPD and healthy controls and to compare KL expression in the locomotor and respiratory muscles.
Methods
KL protein levels were determined from serum in 24 controls and 54 COPD patients and from vastus lateralis biopsies in 15 controls and 63 COPD patients. Other tests were FEV1%pred, fat-free mass index, quadriceps strength (QMVC/BMI) and six-minute walk. 12 COPD patients had vastus lateralis, external intercostal and diaphragm biopsies during routine thoracic surgery, sufficient protein was extracted from 12, 11 and 9 biopsies respectively. KL levels were log transformed, relationship to other parameters was assessed by Pearson’s and differences by t-test or Kruskal-Wallis and post-test Dunn’s.
Results
Serum KL (mean (SD)) was lower in COPD, 2.24 (0.19) v 2.38 (0.19); p=0.003. In COPD, serum KL weakly related to QMVC/BMI (r=0.33, p=0.02), but not with other parameters. Quadriceps KL did not relate to other measurements.
Quadriceps KL was not lower in COPD, 1.56 (0.30) v 1.66 (0.37) p=0.27. Quadriceps KL 1.58 (0.22) was lower than intercostal KL (n=11) 1.86 (0.44); p<0.01 and trended to be lower than diaphragm KL (n=9) 1.76 (0.08).
Conclusions
Serum KL is reduced in COPD and relates to muscle strength. In COPD, the locomotor muscles express lower KL levels than the respiratory muscles; possibly due to different levels of chronic activation. KL may be involved in skeletal muscle adaptation in COPD.
- © 2013 ERS