Circulating MicroRNAs as Specific Biomarkers in Atrial Fibrillation: A Meta-Analysis

Abstract

Atrial fibrillation (AF) is the most frequently occurring supraventricular arrhythmia. Although microRNAs (miRNAs) have been associated with AF pathogenesis, standard protocols for quantifying and selecting specific miRNAs for clinical use as biomarkers should be optimized. In this study, we evaluated the clinical application of miRNAs as biomarkers for the prognosis and diagnosis of AF. Literature searches were conducted on PubMed, Cochrane Library, and EMBASE. We included prospective or retrospective observational studies that had been published as of 14 February 2022; our main objective was to analyze the relationship between circulating miRNAs and AF. The data were extracted using the descriptors “Atrial fibrillation AND miRNA”, “Atrial fibrillation AND diagnostic AND miRNA”, and “Atrial fibrillation AND prognosis AND miRNA”. No filters were applied for period delimitation, type of publication, or language. Studies using samples isolated from blood plasma and TaqMan and RT-qPCR for detecting and quantifying miRNAs were selected, and those that used atrial tissue samples were excluded. We identified 272 articles and excluded 102 duplicated articles. Two authors independently read the titles and abstracts of 170 out of 272 articles and selected 56 potential articles, 6 of which were selected for final review. Our analysis revealed a significant association between AF and miR-4798 [OR = 1.90 (95% CI 1.45–2.47)], AF and miRNA-133a [2.77 (2.73–2.82)], AF and miRNA-150 [3.77 (1.50–9.46); I2 = 70%], AF and miRNA-21 [2.23 (1.20–4.17); I2 = 99%], AF and hsa-miRNA4443 [2.32 (2.20–2.44)], and AF and miR-20a-5p [3.67 (1.42–9.49)]. The association between miRNAs and AF showed an OR of 2.51 [95% CI 1.99–3.16; I2 = 99%]. Our meta-analysis demonstrated that circulating miRNAs are potential biomarkers of AF, as they exhibit stable expression post–sample collection. In addition to regulating cellular processes, such as proliferation, differentiation, development, and cell death, miRNAs were found to be linked to arrhythmia development.

Principles and Limitations of miRNA Purification and Analysis in Whole Blood Collected during Ablation Procedure from Patients with Atrial Fibrillation

“…In a recent meta-analysis, researchers reported miRNA-21 as negative predictor of AF that is associated with the development of myocardial fibrosis. Low expression of miRNA-150 and overexpression of miRNA-133a were also correlated with AF [21]. Other researchers showed a potential use of miRNA-21 as a biomarker of atrial fibrosis in connection with other clinical, echocardiographic, or serological markers [22].…”

Identification of Plasmatic MicroRNA-206 as New Predictor of Early Recurrence of Atrial Fibrillation After Catheter Ablation Using Next-generation Sequencing

“…Various miRNAs, such as miR-4443 [ 27 ] or miR-4798-3p [ 28 ], were identified to be altered between patients with and without AF, while miRNAs such as miR-21 [ 11 , 29 , 30 ], pri-miR-126 [ 31 ], miR-150 [ 11 , 29 ], miR-409-3p and miR-432 [ 32 ] were tested and their levels were shown to be altered before and after CA or between patients with different types of AF. Results of mentioned studies have recently been reviewed in the meta-analysis by Menezes et al [ 33 ]; nevertheless, even the meta-analysis shows that results of the individual studies are conflicting, e.g. higher levels of fibrosis-related miR-21 showed either a decreased [ 11 , 29 ] or increased [ 30 ] chance of AF recurrence after CA.…”

MicroRNAs in Atrial Fibrillation: Mechanisms, Vascular Implications, and Therapeutic Potential

“…Similar to miRNA-21, miRNA-150 is related to changes in levels of interleukins, such as TGF-β, which are involved mainly in the fibrotic processes. Therefore, miRNA-150 may promote atrial fibrillation through its regulation of the inflammatory response system and its impact on fibrosis [23,24].…”