Impact of transcutaneous neuromuscular electrical stimulation or resistance exercise on skeletal muscle mRNA expression in COPD

Abstract

Lorna E Latimer,1,2,* Despina Constantin,3–5,* Neil J Greening,1,2 Lori Calvert,6 Manoj K Menon,7 Michael C Steiner,1,2,* Paul L Greenhaff3–5,*1Department of Respiratory Sciences, University of Leicester, Leicester, UK; 2Institute for Lung Health, National Institute for Health Research (NIHR) Leicester Biomedical Research Centre - Respiratory, Glenfield Hospital, Leicester, UK; 3Medical Research Council/Arthritis Research UK (MRC/ARUK) Centre for Musculoskeletal Ageing Research, University of Nottingham, Nottingham, UK; 4Centre for Sport, Exercise and Osteoarthritis Research, University of Nottingham, Nottingham, UK; 5NIHR Nottingham Biomedical Research Centre, University of Nottingham, Nottingham, UK; 6Peterborough and Stamford Hospitals NHS Foundation Trust, Peterborough City Hospital, Bretton, UK; 7Barking, Havering and Redbridge University Hospitals NHS Trust, Chest Clinic, King George Hospital, Ilford, UK*These authors contributed equally to this work Background: Voluntary resistance exercise (RE) training increases muscle mass and strength in patients with chronic obstructive pulmonary disease (COPD). Nonvolitional transcutaneous neuromuscular electrical stimulation (NMES) may be an alternative strategy for reducing ambulatory muscle weakness in patients unable to perform RE training, but little comparative data are available. This study, therefore, investigated changes in muscle mRNA abundance of a number of gene targets in response to a single bout of NMES compared with RE.Methods: Twenty-six patients with stable COPD (15 male; FEV1, 43±18% predicted; age, 64±8 years; fat free mass index, 16.6±1.8 kg/m2,) undertook 30 minutes of quadriceps NMES (50 Hz, current at the limit of tolerance) or 5×30 maximal voluntary isokinetic knee extensions. Vastus lateralis muscle biopsies were obtained at rest immediately before and 24 hours after intervention. Expression of 384 targeted mRNA transcripts was assessed by real time TaqMan PCR. Significant change in expression from baseline was determined using the ΔΔCT method with a false discovery rate (FDR) of <5%.Results: NMES and RE altered mRNA abundance of 18 and 68 genes, respectively (FDR <5%), of which 14 genes were common to both interventions and of the same magnitude of fold change. Biological functions of upregulated genes included inflammation, hypertrophy, muscle protein turnover, and muscle growth, whilst downregulated genes included mitochondrial and cell signaling functions.Conclusions: Compared with NMES, RE had a broader impact on mRNA abundance and, therefore, appears to be the superior intervention for maximizing transcriptional responses in the quadriceps of patients with COPD. However, if voluntary RE is not feasible in a clinical setting, NMES by modifying expression of genes known to impact upon muscle mass and strength may have a positive influence on muscle function.Keywords: COPD, NMES, skeletal muscle, gene expression, resistance exercise

Keywords

• COPD
• NMES
• skeletal muscle
• gene expression
• resistance exercise.