Obstructive sleep apnea alters microRNA levels: Effects of continuous positive airway pressure

Abstract

Background: Obstructive sleep apnea (OSA) has been linked to cytokine-mediated chronic inflammatory states. Continuous positive airway pressure (CPAP) is an established therapy for OSA, but its effects on inflammation remain unclear. A recent study from our group identified soluble cytokine receptors altered in OSA patients and modified by CPAP adherence. However, the upstream regulatory pathways responsible for these shifts in proinflammatory cascades with OSA and CPAP therapy remained unknown. Accordingly, this study mapped OSA and CPAP-modulated soluble cytokine receptors to specific microRNAs (miRs) and measured those miRs in patients with OSA to test the hypothesis that OSA and CPAP adherence shift cytokine-related miR expression profiles.

Study Design: Plasma samples were collected from patients with OSA (n=50) at baseline and approximately 90 days after CPAP initiation and compared to referent control subjects (n=10). Patients with OSA were further divided into cohorts defined by adherence vs nonadherence to CPAP therapy. MiRs that mapped to soluble cytokine receptors of interest were quantified by PCR analysis.

Results: At baseline, increased hsa-miR-15a-5p, hsa-miR-15b-5p, hsa-miR-16-5p, hsa- miR-195-5p, hsa-miR-424-5p, hsa-miR-223-3p, and hsa-miR-223-5p were observed in patients with OSA compared to controls (p<0.05). In CPAP adherent patients (n=22), hsa-miR233-3p and hsa-miR233-5p decreased at follow-up (p<0.05) whereas there was no change in miR levels from baseline in non-adherent CPAP patients (n=28). The miRs hsa-miR233-3p and hsa-miR233-5p mapped to both proinflammatory and innate immunity activation; the inflammasome.

Interpretation: A specific set of miRs, including hsa-miR233-3p and hsa-miR233-5p, may serve as a marker of inflammatory responses in patients with OSA, and be used to assess attenuation of inflammasome activation by CPAP.