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miR-126a-3p 靶向 HIF-1α,缓解伴高血压的阻塞性睡眠呼吸暂停综合征。

miR-126a-3p targets HIF-1α and alleviates obstructive sleep apnea syndrome with hypertension.

机构信息

Department of Respiratory Medicine, The Second Affiliated Hospital of Nanchang University, No.1 Minde Road, Jiangxi, 330006, China.

出版信息

Hum Cell. 2020 Oct;33(4):1036-1045. doi: 10.1007/s13577-020-00404-z. Epub 2020 Aug 10.

Abstract

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.

摘要

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。

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