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Cellular studies in obstructive lung disease
S49 Increased skeletal muscle-specific microRNA-1 in the blood of COPD patients
  1. A V J Donaldson1,
  2. A Lewis2,
  3. A Natanek1,
  4. W D Man1,
  5. P Kemp2,
  6. M I Polkey1
  1. 1NIHR Respiratory Biomedical Research Unit of Royal Brompton and Harefield NHS Foundation Trust and Imperial College, London UK, London, UK
  2. 2Section of Molecular Medicine, National Heart and Lung Institute, Imperial College London, UK, London, UK

Abstract

Introduction Quadriceps muscle dysfunction is an important prognostic comorbidity in COPD. MicroRNAs (miRs) are small non-coding RNAs that regulate gene expression. Skeletal muscle expresses a number of tissue-specific microRNA including miR-1, which modulates muscle phenotype. MicroRNAs can be secreted from cells and maintained in blood within exosomes. Elevated levels of circulating miR-1 have been demonstrated in a number of human and animal models of muscle disease. We hypothesised that plasma levels of miR-1 would be elevated in COPD patients and would correlate with important physiological parameters.

Methods 103 COPD patients and 25 controls were studied. MiR-1 was quantified in stored plasma samples using q-RT PCR.1 MiR-16 and miR-122 were quantified as negative controls. Results were normalised to an exogenous spiked-in control.

Results Characteristics as mean (SD); COPD patients: M: 67, F: 36, age=66.47 (8.4), FEV1 % pred= 43.5 (18.6), 6-minute walk (6MW) = 394 (120). Controls: M: 14, F: 11, age=67 (8.1), FEV1 % pred=111.2 (13.1), 6MW=613 (83). Plasma miR-1 was significantly elevated in COPD patients, p=0.002. There was no difference in miR-16 and miR-122. MiR-1 was negatively associated with FEV1 % predicted (r =−0.3, p<0.001) and with Tlco (r=−0.3, p<0.001), but it was not possible to distinguish between GOLD stages using ANOVA. However, if patients were sub-divided into early GOLD stage COPD (1 and 2) or late GOLD stage COPD (3 and 4), miR-1 was significantly higher in the latter group (p=0.02). The plasma level of miR-1 was inversely correlated with daily activity measured as locomotion time (r= −0.25, p<0.01) but miR-1 levels were not associated with any muscle phenotype or with muscle-specific gene expression.

Conclusion Our results show that stable COPD patients have elevated plasma levels of muscle-specific miR-1. The increase in miR-1 may be due to increased muscle degradation or turnover in the COPD patients studied. Our work raises the possibility of using other muscle-specific microRNAs in the future as potential biomarkers of muscle dysfunction in patients with COPD.

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