Abstract
Introduction: Pulmonary hypertension is a common complication in patients with severe chronic obstructive pulmonary disease (COPD) but the pathogenesis of its development is not completely understood. MicroRNAs (miRNAs) are small, non-coding gene regulators that have been associated with the pathogenesis of pulmonary hypertension. Here we investigated the signature from miRNAs in lung tissue slides from patients with end-stage COPD with and without elevated pulmonary pressure.
Methods: Paraffin-embedded lung tissue specimens from COPD patients undergoing lung volume reduction surgery (LVRS) or lung transplantation were used. Pulmonary hemodynamics was invasively assessed in all patients before surgery. miRNA isolation was performed using the recoverall total nucleic acid isolation kit (Ambion ®) and quantified by qPCR.
Results: 11 miRNAs previously associated with the pathogenesis of pulmonary hypertension were analysed. Significantly decreased expression levels of miR-125a (-0.54±0.33 vs 0.01±0.65, p<0.01), miR-130a (-0.18±0.43 vs 0.54±0.66, p<0.01), miR-301a (4.49±0.63 vs 5.02±0.71, p<0.05) and miR-424-5p (10.37±0.7 vs 11.43±0.86, p<0.01) were detected in COPD patients with pulmonary hypertension as compared to normotensive controls. A significant inverse association was found between miR-125a, miR-130a and miR-424-5p and mean pulmonary arterial pressure.
Conclusion: This is the first report on the miRNA profile of COPD patients with and without pulmonary hypertension showing that most miRNAs are downregulated in patients with PH-COPD. Further studies are needed to answer the question whether this miRNA profile can be employed as predictor for the presence of an elevated pulmonary pressure in COPD patients.
- Copyright ©ERS 2015