Myositis
Abstract Number 1245 - Resistance Exercise Improves Muscle Function and Reduces the Expression of Inflammation and Fibrosis Genes in Skeletal Muscle of Patients With Polymyositis or Dermatomyositis
AUTHORS: Maryam Dastmalchi1, Gustavo Nader2, Helene Alexanderson1, Christina H. Stenström1, Kanneboyina Nagaraju2, Eric Hoffman2, Ingrid E. Lundberg1. 1Medicine, Stockholm, Sweden; 2Research Center for Genetic Medicine, Children's National Medical Center, WA
PURPOSE: To better understand whether resistive physical exercise has beneficial effects on patients with polymyositis (PM) or dermatomyositis (DM), this group carried out a seven week resistance training program in patients diagnosed with PM or DM. To further understand the molecular mechanisms underlying the effects of exercise, muscle biopsies were obtained and subjected to a genome-wide analysis of gene expression.
METHODS: Eight patients with stable PM or DM underwent a whole body resistance training program 3 times a week for 7 weeks. Muscles biopsies were obtained from the vastus lateralis muscle before and one week following the last training session and RNA was extracted and prepared for expression profiling using the Affymetrix Human Genome U133 Plus.2 chips. Absolute expression values were calculated using MAS.5 and data analysis carried out in Gene Spring. Statistical significance was determined for those genes that changed >1.5 fold and were significantly different at p<0.05.
RESULTS: The group improved significantly regarding muscle strength (10-15 VRM) in four muscle groups including quadriceps. Resistance training with improved muscle function in PM or DM patients resulted in the expression of genes involved in inflammation (e.g. MHC-1F, HMGB1, IRAK3, IL2R, IL10R), fibrosis (FGF1, CTGF, Collagens IA and XIVA), and also by modulating genes involved in protein degradation (Cathepsin C) as well as in muscle metabolism (AK3 and UCP3 ).
CONCLUSION: The authors concluded that regular physical activity can improve muscle function in PM or DM patients, suggesting that such improvement may result from the “coordinated” induction of skeletal muscle structural and metabolic remodeling together with a reduction in fibrosis and inflammation. This was studied at the genomic level by expression profiling.
COMMENT: This study suggests that supervised resistance exercise should be considered as a treatment for patients with PM or DM. It is a provocative study design which attempts to find an association of muscle strength improvement with down-regulated gene expression in clinically-relevant subsets, mainly the inflammation and fibrosis pathway as well as modulation of those involved in protein degradation and muscle metabolism. This was a bold study utilizing muscle tissue samples for the gene analysis and the first of its kind to demonstrate a correlation between exercise-related improved muscle strength and mechanistically relevant gene expression. The downside is that it lacks a control group, but because of the invasive nature of a muscle biopsy, appropriate controls may be difficult to recruit. It would be helpful to explore gene expression profiles in normal controls and patients with muscle diseases other than myositis who are subjected to the same resistance training exercise regimen.