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. 2023 Oct 17;24(20):15248.
doi: 10.3390/ijms242015248.

Plasma miR-486-5p Expression Is Upregulated in Atrial Fibrillation Patients with Broader Low-Voltage Areas

María Cebro-Márquez  1   2   3 , Moisés Rodríguez-Mañero  2   3 , Valentina Serrano-Cruz  1   2 , Marta E Vilar-Sánchez  1   2 , Laila González-Melchor  2 , Javier García-Seara  2   3 , José Luis Martínez-Sande  2   3 , Alana Aragón-Herrera  2   3   4 , María Amparo Martínez-Monzonís  2   3 , José Ramón González-Juanatey  2   3 , Ricardo Lage  1   2   3   5 , Isabel Moscoso  1   2   3
Affiliations

Plasma miR-486-5p Expression Is Upregulated in Atrial Fibrillation Patients with Broader Low-Voltage Areas

María Cebro-Márquez et al. Int J Mol Sci. .

Abstract

Atrial fibrillation (AF) is the most common arrhythmia worldwide, affecting 1% of the population over 60 years old. The incidence and prevalence of AF are increasing globally, representing a relevant health problem, suggesting that more advanced strategies for predicting risk stage are highly needed. miRNAs mediate several processes involved in AF. Our aim was to identify miRNAs with a prognostic value as biomarkers in patients referred for AF ablation and its association with LVA extent, based on low-voltage area (LVA) maps. In this study, we recruited 44 AF patients referred for catheter ablation. We measured the expression of 84 miRNAs in plasma from peripheral blood in 3 different groups based on LVA extent. Expression analysis showed that miR-486-5p was significantly increased in patients with broader LVA (4-fold, p = 0.0002; 5-fold, p = 0.0001). Receiver operating characteristic curve analysis showed that miR-486-5p expression could predict atrium LVA (AUC, 0.8958; p = 0.0015). Also, miR-486-5p plasma levels were associated with AF-type (AUC, 0.7137; p = 0.0453). In addition, miR-486-5p expression was positively correlated with LVA percentage, left atrial (LA) area, and LA volume (r = 0.322, p = 0.037; r = 0.372, p = 0.015; r = 0.319, p = 0.045, respectively). These findings suggest that miR-486-5p expression might have prognostic significance in LVA extent in patients with AF.

Keywords: atrial fibrillation; biomarkers; low-voltage areas; miR-486-5p; microRNAs.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
(a) Differential expression levels of miRNAs in AF patients between groups in plasma from peripheral blood. (b) Predictive capacity of LVA stage. Receiver operating characteristic curves comparing sensitivity and specificity of plasma from peripheral blood differentially expressed miR-486-5p in predicting LVA percentage. Data are presented as mean ± S.E.M. *** p < 0.001 vs. Stage 1 and ### p < 0.01 vs. Stage 2.
Figure 2
Figure 2
Association between LVA percentage and AF type. (a) LVA percentage in paroxysmal, persistent, and LS persistent patients. (b) Receiver operating characteristic curve comparing sensitivity and specificity of LVA in paroxysmal and LS persistent patients. Data are presented as mean ± S.E.M. * p< 0.05 vs. paroxysmal.
Figure 3
Figure 3
(a) Differential expression of miRNAs in paroxysmal, persistent, and long-standing persistent AF patients in plasma from peripheral blood. (b) Predictive capacity of AF type. Receiver operating characteristic (ROC) curves comparing sensitivity and specificity of hsa-miR-486-5p differentially expressed in persistent and long-standing persistent patients in plasma from peripheral blood. Data are presented as mean ± S.E.M. * p < 0.05, *** p < 0.001 vs. paroxysmal and, ### p < 0.001 vs. persistent.
Figure 4
Figure 4
Correlation of has-miR-486-5p expression with echocardiography data. (a) Correlation with LVA percentage. (b) Correlation with LA area. (c) Correlation with LA volume.
Figure 5
Figure 5
miRNA–genes–pathways network denoting the relationships between miR-486-5p, validated target genes, and those related to KEGG pathways, created in Cytoscape.
Figure 6
Figure 6
Overview of miR-486-5p target genes (miRTarBase) and possible pathological effects on AF fibrosis progression. Created with BioRender. MFE: minimum free energies.
See this image and copyright information in PMC

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