Investigating circulating microRNAs as potential biomarkers of quadriceps weakness in COPD

Abstract

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