Circulating Plasma Exosomes in Obstructive Sleep Apnea and Reverse-Dipping Blood Pressure

Background Obstructive Sleep Apnea (OSA) increases the risk of abnormal non-dipping 24-hour blood pressure profile, an independent risk factor for cardiovascular disease (CVD). We examined differential exosomal miRNA expression in untreated OSA patients with normal dipping blood pressure (NDBP) and reverse dipping blood pressure (RDBP; an extreme form of non-dipping) to understand the mechanisms underlying non-dipping blood pressure in OSA.

Methods 46 patients (RDBP, n=15 versus NDBP, n=31) matched for OSA severity (respiratory event index, 32.6±22.5 h⁻¹ versus 32.2±18.1 h⁻¹, p=0.9), age (54.8±12.9 versus 49±9.9 years, p=0.09) and body mass index (36.2±6.6 kg·m⁻² versus 34.4±6.8 kg·m⁻², p=0.4) were included. Plasma exosomes were characterised by flow cytometry, and functional in vitro reporter assays were conducted on cultured endothelial cells. Exosome miRNA cargo was profiled with microarrays followed by bioinformatics analyses.

Results Exosomes from RDBP patients increased the permeability of endothelial cell tight-junctions and adhesion molecule expression. Principal component analyses of miRNA array data showed strict separation and identification of the two groups. A restricted and validated signature of exosomal miRNAs were identified in RDBP versus NDBP group. Their predicted target genes involved PI3K-Akt (p=0.004), Ras (p=3.42E-05), Wnt (p=0.003), and HIF-1 signalling (p=0.04), inflammatory mediator regulation of TRP channels (p=0.01), and several cancer-related pathways.

Conclusions Patients with RDBP have altered miRNA cargo in circulating exosomes that invoke in vitro endothelial dysfunction. A selected number of circulating exosomal miRNAs play an important role in abnormal circadian regulation of blood pressure and may provide prognostic biomarkers of CVD risk in OSA.