Endurance Exercise Improves Molecular Pathways of Aerobic Metabolism in Patients With Myositis

Abstract

Objective Endurance exercise demonstrates beneficial effects in polymyositis/dermatomyositis (PM/DM); however, the molecular effects of exercise on skeletal muscle are incompletely understood. We undertook this controlled pilot study to investigate the effects of a 12‐week endurance exercise training program on the molecular profile of skeletal muscle in patients with established PM/DM compared to a nonexercised control group of patients with established PM/DM. Methods Fifteen patients (7 in the exercise group and 8 in the control group) with paired baseline and 12‐week follow‐up muscle biopsy samples were included. Messenger RNA expression profiling, mass spectrometry–based quantitative proteomics, and immunohistochemical analyses were performed on muscle biopsy samples to determine molecular adaptations associated with changes in clinical measurements induced by endurance exercise. Results Compared to the control group, the exercise group improved in minutes of cycling time (P < 0.01) and Vo2 max (P < 0.05). The exercise group also had reduced disease activity (P < 0.05) and reduced lactate levels at exhaustion (P < 0.05). Genes related to capillary growth, mitochondrial biogenesis, protein synthesis, cytoskeletal remodeling, and muscle hypertrophy were up‐regulated in the exercise group, while genes related to inflammation/immune response and endoplasmic reticulum stress were down‐regulated. Mitochondrial pathways including the oxidative phosphorylation metabolic pathway were most affected by the endurance exercise, as demonstrated by proteomics analysis. The exercise group also showed a higher number of capillaries per mm2 in follow‐up biopsy samples (P < 0.05). Conclusion Our data indicate that endurance exercise in patients with established PM and DM may activate an aerobic phenotype and promote muscle growth and simultaneously suppress the inflammatory response in these patients’ muscles, as supported by a combination of data on gene expression, proteomics, and capillary density in repeated muscle biopsies.

Mitochondrial dysfunction and role of harakiri in the pathogenesis of myositis

“…Previous studies have shown that endurance exercise improves mitochondrial function by increasing expression of components required for oxidative phosphorylation . This was seen at the functional level in myositis patients with exercise resulting in increased aerobic capacity after 12 week .…”

“…Deidentified PM and DM biopsies ( n = 8) and healthy muscle biopsies ( n = 4) were obtained from Dr Ingrid Lundberg, Karolinska Institutet for exercise studies as described previously . In brief, muscle biopsies were frozen in liquid nitrogen‐cooled isopentane, and stored at −80 °C until analysis.…”

“…Historically, due to the characteristic signs of muscle damage and inflammation, physicians have avoided prescribing exercise to improve mitochondrial function in myositis patients. Recently, by analyzing the transcriptomic and proteomic changes in myositis patients after 12 week of endurance exercise training, we described that genes related to mitochondrial health and biogenesis were upregulated, which correlated with improved measures of skeletal muscle performance in these patients . Aside from the widely recognized metabolic role of mitochondria in skeletal muscle, we have previously identified a role of mitochondria in facilitating the repair of injured skeletal myofibers .…”

Omics and Exercise: Global Approaches for Mapping Exercise Biological Networks

“…Although not discussed in detail, small noncoding RNA molecules such as microRNA are also important contributors to exercise-regulated posttranscriptional modulation and represent an exciting area for future investigation in epigenetic control of the exercise response (as systematically reviewed in Flowers et al 2015). (Schild et al 2015), myositis (Munters et al 2016), and type 2 diabetes (T2D) (Hussey et al 2013) relevant to muscle metabolic health has been uncovered using proteomics. Bioinformatics analysis of network adaptations has revealed important exercise variables underlying skeletal muscle (Padrao et al 2016) and heart (Ferreira et al 2015) plasticity.…”

The Clinical and Pathological Spectrum of Idiopathic Inflammatory Myopathies : Implications for pathogenesis, classification and diagnosis

“…For patients with a coexistent interstitial lung disease cyclophosphamide or tacrolimus are recommended [282,283]. Structured exercise programs have shown positive short term effects on muscle strength, and also to have favorable effects on gene expression and capillary density in muscles, of IIM patients [284,285].…”