title: A longitudinal, integrated, clinical, histological and mRNA profiling study of resistance exercise in myositis.
abstract: Polymyositis and dermatomyositis are orphan, chronic skeletal muscle disorders characterized by weakness, infiltrations by mononuclear inflammatory cells, and fibrosis. Until recently, patients were advised to refrain from physical activity because of fears of exacerbation of muscle inflammation. However, recent studies have shown that moderate exercise training in combination with immunosuppressive drugs can improve muscle performance. Despite the positive effects of exercise training, the molecular mechanisms underlying the exercise-associated clinical improvements remain poorly understood. The present study was designed to define, at the molecular level, the effects of resistance exercise training on muscle performance and disease progression in myositis patients. We evaluated changes in muscle strength, histology and genome-wide mRNA profiles to determine the beneficial effects of exercise and determine the possible molecular changes associated with improved muscle performance. A total of 8 myositis patients underwent a 7-wk resistance exercise training program that resulted in improved muscle strength and increased maximal oxygen uptake (VO(2max)). Training also resulted in marked reductions in gene expression, reflecting reductions in proinflammatory and profibrotic gene networks, changes that were also accompanied by a reduction in tissue fibrosis. Consistent with the exercise-associated increase in VO(2max), a subset of transcripts was associated with a shift toward oxidative metabolism. The changes in gene expression reported in the present study are in agreement with the performance improvements induced by exercise and suggest that resistance exercise training can induce a reduction in inflammation and fibrosis in skeletal muscle.
authors.affiliation: Research Center for Genetic Medicine, Children's National Medical Center, Washington, DC, USA.
authors.forename: Gustavo A
authors.initials: GA
authors.lastname: Nader
authors.forename: Maryam
authors.initials: M
authors.lastname: Dastmalchi
authors.forename: Helene
authors.initials: H
authors.lastname: Alexanderson
authors.forename: Cecilia
authors.initials: C
authors.lastname: Grundtman
authors.forename: Ramkishore
authors.initials: R
authors.lastname: Gernapudi
authors.forename: Mona
authors.initials: M
authors.lastname: Esbjörnsson
authors.forename: Zuyi
authors.initials: Z
authors.lastname: Wang
authors.forename: Johan
authors.initials: J
authors.lastname: Rönnelid
authors.forename: Eric P
authors.initials: EP
authors.lastname: Hoffman
authors.forename: Kanneboyina
authors.initials: K
authors.lastname: Nagaraju
authors.forename: Ingrid E
authors.initials: IE
authors.lastname: Lundberg
mesh_terms: D000328:Adult; D005355:Fibrosis / Q000378:metabolism; D020869:Gene Expression Profiling; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007249:Inflammation / Q000378:metabolism; D008137:Longitudinal Studies; D008875:Middle Aged; D053580:Muscle Strength; D018482:Muscle, Skeletal / Q000378:metabolism; D009220:Myositis / Q000628:therapy*; D010101:Oxygen Consumption / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism*; D055070:Resistance Training
chemical_list: D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D012333:RNA, Messenger
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