RT Journal Article
SR Electronic
T1 Investigating circulating microRNAs as potential biomarkers of quadriceps weakness in COPD
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 206
VO 38
IS Suppl 55
A1 Donaldson, Anna
A1 Lewis, Amy
A1 Natanek, Samantha
A1 Man, William
A1 Kemp, Paul
A1 Polkey, Michael
YR 2011
UL https://publications.ersnet.org//content/38/Suppl_55/206.abstract
AB Introduction: Non-invasive biomarkers of quadriceps phenotype in COPD are needed. MicroRNAs (mirs) are small non-coding RNA that modulate gene expression. They circulate in blood as exosomes and are promising biomarkers. We hypothesised that muscle specific mir-499, which controls slow myosin expression, would be differentially expressed and correlate with physiological parameters.Methods: We studied 101 COPD patients and 24 controls. Mir-499 was quantified in stored plasma samples using q-RT PCR1. Mir-16 and mir-122 were quantified as negative controls. Results were normalised to a spiked-in control. All subjects had paired quadriceps biopsy samples.Results: Characteristics as mean (SD); COPD patients: 66 M: 35 F, age= 66 (8), FEV1% pred= 44 (19), six-minute walk (6MW)= 394 (121). Controls: 14 M: 10 F, age 66 (8), FEV1% pred= 112 (13), 6MW= 616 (83).Plasma mir-499 was significantly elevated in COPD patients, p= 0.0036. There was no difference in mir-16 and mir-122.Mir-499 levels negatively correlated with total fibre cross sectional area (P= 0.03 R2= 0.04) and in the patients there was a weak positive correlation with 6MW (p=0.047 R2= 0.0016). Patients with no quadriceps muscle fibre type shift (defined from the control samples) had higher mir-499 (p= 0.02).Conclusion: We have demonstrated a difference in plasma mir-499 levels between COPD patients and controls. Higher mir-499 in patients with no fibre type shift is consistent with its proposed role of maintaining a high endurance skeletal myofibre phenotype. Our results may reflect higher protein turnover in COPD and contribute towards developing a blood-borne biomarker to stratify treatment.1Kroh, Methods 50 (2010)298–301