Publications
514 results found
Lewis A, Donaldson AV, Natanek SA, et al., 2016, Increased expression of H19/miR-675 is associated with a low fat free mass index in patients with COPD, Journal of Cachexia, Sarcopenia and Muscle, Vol: 7, Pages: 330-344, ISSN: 2190-6009
BackgroundLoss of muscle mass and strength is a significant comorbidity in patients with chronic obstructive pulmonary disease (COPD) that limits their quality of life and has prognostic implications but does not affect everyone equally. To identify mechanisms that may contribute to the susceptibility to a low muscle mass, we investigated microRNA (miRNA) expression, methylation status, and regeneration in quadriceps muscle from COPD patients and the effect of miRNAs on myoblast proliferation in vitro. The relationships of miRNA expression with muscle mass and strength was also determined in a group of healthy older men.MethodsWe identified miRNAs associated with a low fat-free mass (FFM) phenotype in a small group of patients with COPD using a PCR screen of 750 miRNAs. The expression of two differentially expressed miRNAs (miR-675 and miR-519a) was determined in an expanded group of COPD patients and their associations with FFM and strength identified. The association of these miRNAs with FFM and strength was also explored in a group of healthy community-dwelling older men. As the expression of the miRNAs associated with FFM could be regulated by methylation, the relative methylation of the H19 ICR was determined. Furthermore, the proportion of myofibres with centralized nuclei, as a marker of muscle regeneration, in the muscle of COPD patients was identified by immunofluorescence.ResultsImprinted miRNAs (miR-675 and from a cluster, C19MC which includes miR-519a) were differentially expressed in the quadriceps of patients with a low fat-free mass index (FFMI) compared to those with a normal FFMI. In larger cohorts, miR-675 and its host gene (H19) were higher in patients with a low FFMI and strength. The association of miR-519a expression with FFMI was present in male patients with severe COPD. Similar associations of miR expression with lean mass and strength were not observed in healthy community dwelling older men participating in the Hertfordshire Sarcopenia Stu
Curtis KJ, Meyrick VM, Mehta B, et al., 2016, Angiotensin-Converting Enzyme Inhibition As An Adjunct To Pulmonary Rehabilitation: A Randomised Controlled Trial, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Buttery SC, Mohan D, Fisk M, et al., 2016, Longitudinal Follow-Up Of A Chronic Obstructive Pulmonary Disease Cohort After 3 Years: Changes In Quadriceps Strength, Aortic Pulse Wave Velocity And Blood Biomarkers, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Boutou AK, Polkey MI, Hopkinson NS, 2016, Erratum: Non-anaemic iron deficiency in COPD: A potential therapeutic target? (Respirology (2015) 20 (1004-1005)), Respirology, Vol: 21, Pages: 196-196, ISSN: 1323-7799
Patel MS, Lee J, Baz M, et al., 2015, Growth differentiation factor-15 is associated with muscle mass in chronic obstructive pulmonary disease and promotes muscle wasting in vivo, Journal of Cachexia, Sarcopenia and Muscle, Vol: 7, Pages: 436-448, ISSN: 2190-6009
BackgroundLoss of muscle mass is a co-morbidity common to a range of chronic diseases including chronic obstructive pulmonary disease (COPD). Several systemic features of COPD including increased inflammatory signalling, oxidative stress, and hypoxia are known to increase the expression of growth differentiation factor-15 (GDF-15), a protein associated with muscle wasting in other diseases. We therefore hypothesized that GDF-15 may contribute to muscle wasting in COPD.MethodsWe determined the expression of GDF-15 in the serum and muscle of patients with COPD and analysed the association of GDF-15 expression with muscle mass and exercise performance. To determine whether GDF-15 had a direct effect on muscle, we also determined the effect of increased GDF-15 expression on the tibialis anterior of mice by electroporation.ResultsGrowth differentiation factor-15 was increased in the circulation and muscle of COPD patients compared with controls. Circulating GDF-15 was inversely correlated with rectus femoris cross-sectional area (P < 0.001) and exercise capacity (P < 0.001) in two separate cohorts of patients but was not associated with body mass index. GDF-15 levels were associated with 8-oxo-dG in the circulation of patients consistent with a role for oxidative stress in the production of this protein. Local over-expression of GDF-15 in mice caused wasting of the tibialis anterior muscle that expressed it but not in the contralateral muscle suggesting a direct effect of GDF-15 on muscle mass (P < 0.001).ConclusionsTogether, the data suggest that GDF-15 contributes to the loss of muscle mass in COPD.
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