Background Obstructive sleep apnoea (OSA) increases the risk of an abnormal nondipping 24 h blood pressure profile, an independent risk factor for cardiovascular disease (CVD). We examined differential exosomal microRNA (miRNA) expression in untreated OSA patients with normal dipping blood pressure (NDBP) and reverse dipping blood pressure (RDBP), an extreme form of nondipping, to understand the mechanisms underlying nondipping blood pressure in OSA. Methods 46 patients (15 RDBP versus 31 NDBP) matched for OSA severity (respiratory event index 32.6±22.5 versus 32.2±18.1 events·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 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 was identified in the RDBP versus NDBP group. Their predicted target genes involved phosphatidylinositol 3-kinase-Akt (p=0.004), Ras (p=3.42E-05), Wnt (p=0.003) and hypoxia inducible factor-1 signalling (p=0.04), inflammatory mediator regulation of transient receptor potential channels (p=0.01), and several cancer-related pathways. Conclusions Patients with RDBP have altered miRNA cargoes 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. A selected number of circulating exosomal miRNAs play an important role in abnormal circadian regulation of blood pressure and may provide prognostic biomarkers of cardiovascular risk in OSA http://bit.ly/2VPRFl4

中文翻译：

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循环血浆外泌体在阻塞性睡眠呼吸暂停和反倾角血压中的作用

背景 阻塞性睡眠呼吸暂停 (OSA) 会增加 24 小时非浸没血压异常的风险，这是心血管疾病 (CVD) 的独立危险因素。我们检查了未治疗的具有正常浸渍血压 (NDBP) 和反向浸渍血压 (RDBP)（非浸渍的一种极端形式）的未治疗 OSA 患者的差异外泌体 microRNA (miRNA) 表达，以了解 OSA 中非浸渍血压的潜在机制。方法 46 名患者（15 RDBP 与 31 NDBP）匹配 OSA 严重程度（呼吸事件指数 32.6±22.5 与 32.2±18.1 事件·h-1；p=0.9）、年龄（54.8±12.9 与 49±9.9 岁；p=0.09 ）和体重指数（36.2±6.6 vs 34.4±6.8 kg·m-2；p=0.4）。血浆外泌体通过流式细胞术表征，并对培养的内皮细胞进行功能性体外报告基因检测。外泌体 miRNA 货物用微阵列分析，然后进行生物信息学分析。结果 RDBP 患者的外泌体增加了内皮细胞紧密连接的通透性和粘附分子的表达。miRNA 阵列数据的主成分分析显示两组的严格分离和鉴定。在 RDBP 与 NDBP 组中发现了外泌体 miRNA 的受限且经过验证的特征。他们预测的靶基因涉及磷脂酰肌醇 3-激酶-Akt（p=0.004）、Ras（p=3.42E-05）、Wnt（p=0.003）和缺氧诱导因子-1 信号（p=0.04）、炎症介质调节瞬时受体电位通道 (p=0.01) 和几种癌症相关通路。结论 RDBP 患者改变了循环外泌体中的 miRNA 载量，从而引起体外内皮功能障碍。选定数量的循环外泌体 miRNA 在血压异常昼夜节律调节中发挥重要作用，并可能提供 OSA 中 CVD 风险的预后生物标志物。选定数量的循环外泌体 miRNA 在血压异常昼夜节律调节中发挥重要作用，并可能提供 OSA 心血管风险的预后生物标志物 http://bit.ly/2VPRFl4