Group of Precision Medicine in Chronic Diseases, Hospital Universitari Arnau de Vilanova-Santa Maria, IRB Lleida, Lleida, Spain.
Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain.
Respiration. 2021;100(4):298-307. doi: 10.1159/000511963. Epub 2021 Feb 5.
Several studies have reported an association between microRNAs (miRNAs) and hypertension or cardiovascular disease (CVD). In a previous study performed on a group of 38 patients, we observed a cluster of 3 miRNAs (miR-378a-3p, miR-100-5p, and miR-486-5p) that were functionally associated with the cardiovascular system that predicted a favorable blood pressure (BP) response to continuous positive airway pressure (CPAP) treatment in patients with resistant hypertension (RH) and obstructive sleep apnea (OSA) (HIPARCO score). However, little is known regarding the molecular mechanisms underlying this phenomenon.
The aim of the study was to perform a post hoc analysis to investigate the genes, functions, and pathways related to the previously found HIPARCO score miRNAs.
We performed an enrichment analysis using Ingenuity pathway analysis. The genes potentially associated with the miRNAs were filtered based on their confidence level. Particularly for CVD, only the genes regulated by at least 2 of the miRNAs were studied.
We observed that the miRNAs studied regulate 200-249 molecules associated with several functions and diseases, including extracranial solid tumors and abdominal neoplasms, among others. The cardiac hypertrophy and NF-kB signaling pathways were identified as the cardiovascular pathways most influenced by these 3 miRNAs.
The mechanisms by which CPAP treatment decreases the BP in OSA patients with RH could be related to the cardiac hypertrophy and NF-kB signaling pathways. Further investigations will be necessary to confirm these findings, contributing to the elucidation of new therapeutic targets in patients who do not respond to CPAP treatment.
多项研究报道了 microRNAs(miRNAs)与高血压或心血管疾病(CVD)之间的关联。在之前对 38 名患者进行的一项研究中,我们观察到一组 3 个 miRNAs(miR-378a-3p、miR-100-5p 和 miR-486-5p)的聚类,这些 miRNAs 与心血管系统功能相关,可预测对患有难治性高血压(RH)和阻塞性睡眠呼吸暂停(OSA)患者的持续气道正压通气(CPAP)治疗有良好的血压(BP)反应(HIPARCO 评分)。然而,对于这种现象背后的分子机制,我们知之甚少。
本研究的目的是进行事后分析,以研究与之前发现的 HIPARCO 评分 miRNAs 相关的基因、功能和途径。
我们使用 Ingenuity 通路分析进行了富集分析。根据置信度水平筛选出与 miRNA 潜在相关的基因。特别是对于 CVD,只研究了至少被 2 个 miRNA 调控的基因。
我们观察到研究的 miRNAs 调节了 200-249 个与多种功能和疾病相关的分子,包括颅外实体瘤和腹部肿瘤等。心脏肥大和 NF-kB 信号通路被确定为受这 3 个 miRNA 影响最大的心血管途径。
CPAP 治疗降低 RH 合并 OSA 患者血压的机制可能与心脏肥大和 NF-kB 信号通路有关。需要进一步的研究来证实这些发现,有助于阐明对 CPAP 治疗无反应的患者的新治疗靶点。