Department of Respiratory Medicine, The Second Affiliated Hospital of Nanchang University, No.1 Minde Road, Jiangxi, 330006, China.
Hum Cell. 2020 Oct;33(4):1036-1045. doi: 10.1007/s13577-020-00404-z. Epub 2020 Aug 10.
The obstructive sleep apnea syndrome (OSAS) is a common sleep-related breathing disorder and an important cause of refractory hypertension. MicroRNAs (miRNAs) are involved in the development of hypertension, but their role in OSAS with hypertension (OSAS-hypertension) has been little studied. Evidence indicates that miR-126a-3p expression is lower in patients with OSAS-hypertension compared with the patients with OSAS alone. However, its role in the pathogenesis of OSAS-hypertension remains unclear. Therefore, this study aims to investigate the role of miR-126a-3p in OSAS-hypertension and to determine whether HIF-1α is involved in this process. Sprague Dawley rats were exposed to chronic intermittent hypoxia (CIH) for 8 weeks to induce OSAS-hypertension. Rat aortic smooth muscle cells (A7r5) were cultured under hypoxia as an in vitro model. Our results showed that rats exposed to 8 week CIH exhibited decreased miR-126a-3p and increased HIF-1α expression. Furthermore, administration of recombinant adeno-associated virus expressing miR-126a-3p (rAAV-miR-126a) counteracted the CIH-induced systolic blood pressure upregulation, oxidase stress, inflammation, and heart and abdominal aorta vascular remodeling. Moreover, the mechanism was associated with its targeted suppression of HIF-1α. These findings suggest that miR-126a-3p might be a novel potential therapeutic target for the treatment of OSAS-hypertension.
阻塞性睡眠呼吸暂停综合征(OSAS)是一种常见的与睡眠相关的呼吸障碍,也是难治性高血压的重要原因。MicroRNAs(miRNAs)参与高血压的发生,但它们在伴有高血压的 OSAS(OSAS-高血压)中的作用研究甚少。有证据表明,与单纯 OSAS 患者相比,OSAS-高血压患者的 miR-126a-3p 表达水平较低。然而,其在 OSAS-高血压发病机制中的作用尚不清楚。因此,本研究旨在探讨 miR-126a-3p 在 OSAS-高血压中的作用,并确定 HIF-1α 是否参与这一过程。将 Sprague Dawley 大鼠暴露于慢性间歇性缺氧(CIH)8 周以诱导 OSAS-高血压。将大鼠主动脉平滑肌细胞(A7r5)在低氧条件下培养作为体外模型。我们的结果表明,暴露于 8 周 CIH 的大鼠表现出 miR-126a-3p 表达降低和 HIF-1α 表达增加。此外,给予表达 miR-126a-3p 的重组腺相关病毒(rAAV-miR-126a)可逆转 CIH 引起的收缩压升高、氧化应激、炎症以及心脏和腹主动脉血管重塑。此外,其机制与靶向抑制 HIF-1α 有关。这些发现表明,miR-126a-3p 可能是治疗 OSAS-高血压的一种新的潜在治疗靶点。