Distinct Intramuscular Extracellular Matrix Protein Responses to Exercise Training in COPD and Healthy Adults and Their Association with Muscle Remodeling

Background: The skeletal muscle extracellular matrix (ECM) is critical for muscle force and the regulation of important physiological processes. A growing body of evidence demonstrates that in aging, altered ECM composition profoundly hinders the capacity for muscle adaptation in response to exercise training. We evaluated the pattern of ECM expression in response to exercise training between healthy young participants and patients with chronic obstructive pulmonary disease (COPD), to provide insight into how normal adaptive processes differ under conditions of chronic disease. Methods: Vastus lateralis muscle biopsies from 29 patients (mean ± SD FEV1: 43 ± 16% predicted) and 14 healthy subjects were analyzed before and after an interval exercise training program for myofiber distribution and size. A selection of ECM molecules was quantified using ELISA. Results: Compared to healthy participants, patients exhibited a lower capacity to increase myofiber type I distribution (by 4.7 ± 3.4 vs. 1.3 ± 2.2%) and mean fiber cross-sectional area (by 13.6 ± 3.2 vs. 9.1 ± 1.9%). Exercise training induced a diverse protein expression between the two cohorts in ECMs regulating tissue structure (collagens: up-regulated only in COPD), myogenesis (SPARC: up-regulated only in healthy), necroptosis (tenascin C: up-regulated only in COPD), adherence to muscle-cell precursors (Fibronectin: up-regulated only in healthy) and tissue integrity (biglycan: down-regulated only in COPD). Conclusions: Impaired ECM remodeling may underlie the reduced exercise training muscle adaptation observed in COPD patients.