Gene networks and canonical pathways associated with a favorable blood pressure response after CPAP treatment: the HIPARCO score post hoc analysis

Abstract

Background: Several studies report an association between microRNAs (miRNAs) and hypertension or cardiovascular disease. In a previous study, we observed a cluster of three miRNAs (miR-378a-3p, miR-100-5p, and miR-486-5p) functionally associated with the cardiovascular system that predicted a favorable blood pressure 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. Thus, the aim of the present study was to perform a post hoc analysis to investigate the genes, functions and pathways related to the previously found HIPARCO-score miRNAs. Methods: 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 cardiovascular disease, only the genes regulated by at least two of the miRNAs were studied. Results: 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 three miRNAs. Conclusions: Considering this, the mechanisms by which CPAP treatment decreases the blood pressure in OSA patients with RH could be related to these pathways. Further investigations will be necessary to confirm these findings, contributing to the elucidation of new therapeutic targets in patients that do not respond to CPAP treatment.

The Effect of Continuous Positive Airway Pressure Therapy on Obstructive Sleep Apnea-Related Hypertension

“…Other studies have proposed an involvement of activated platelets in the development of OSA-related cardiovascular complications [ 36 ] and a post hoc miRNA analysis has identified three miRNAs (miR-378a-3p, miR-100-5p and miR-486-5p) that were associated to a favorable CPAP treatment outcome of OSA-related HT. The pathways mostly affected by these miRNAs are the cardiac hypertrophy and NF-kB signaling pathways [ 37 ].…”