Dataset Information

Increased small extracellular vesicle levels and decreased miR-126 levels associated with atrial fibrillation and coexisting diabetes mellitus.

ABSTRACT:

Background

Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia. Diabetes mellitus (DM) is one of the risk factors for the development of stroke and thromboembolism in patients with AF. Early identification may reduce the incidence of complications and mortality in AF patients.

Hypothesis

AF patients with DM have different pattern of small extracellular vesicle (sEV) levels and sEV-derived microRNA (miRNA) expression compared with those without DM.

Methods

We compared sEV levels and sEV-miRNA expression in plasma from AF patients with and without DM using nanoparticle tracking analysis and droplet digital polymerase chain reaction, respectively.

Results

We observed a significant increase in total sEV levels (p = .004) and a significant decrease in sEV-miR-126 level (p = .004) in AF patients with DM. Multivariate logistic regression analysis revealed a positive association between total sEV levels and AF with DM (p = .019), and a negative association between sEV-miR-126 level and AF with DM (p = .031). The combination of clinical data, total sEVs, and sEV-miR-126 level had an area under the curve of 0.968 (p < .0001) for discriminating AF with DM, which was shown to be significantly better than clinical data analysis alone (p = .0368).

Conclusions

These results suggest that an increased level of total sEV and a decreased sEV-miR-126 level may play a potential role in the pathophysiology and complications of AF with DM, especially endothelial dysfunction, and can be considered as an applied biomarker for distinguishing between AF with and without DM.

SUBMITTER: Siwaponanan P

PROVIDER: S-EPMC10642338 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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Publications

Increased small extracellular vesicle levels and decreased miR-126 levels associated with atrial fibrillation and coexisting diabetes mellitus.

Siwaponanan Panjaree P Kaewkumdee Pontawee P Sudcharee Payalak P Udompunturak Suthipol S Chomanee Nusara N Udol Kamol K Pattanapanyasat Kovit K Krittayaphong Rungroj R

Clinical cardiology 20230807 11

<h4>Background</h4>Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia. Diabetes mellitus (DM) is one of the risk factors for the development of stroke and thromboembolism in patients with AF. Early identification may reduce the incidence of complications and mortality in AF patients.<h4>Hypothesis</h4>AF patients with DM have different pattern of small extracellular vesicle (sEV) levels and sEV-derived microRNA (miRNA) expression compared with those without DM.<h4>Methods</h4>We c ...[more]

PMID: 37503820

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Project description:BackgroundsNon-valvular atrial fibrillation (AF) is the most common type of cardiac arrhythmia. AF is caused by electrophysiological abnormalities and alteration of atrial tissues, which leads to the generation of abnormal electrical impulses. Extracellular vesicles (EVs) are membrane-bound vesicles released by all cell types. Large EVs (lEVs) are secreted by the outward budding of the plasma membrane during cell activation or cell stress. lEVs are thought to act as vehicles for miRNAs to modulate cardiovascular function, and to be involved in the pathophysiology of cardiovascular diseases (CVDs), including AF. This study identified lEV-miRNAs that were differentially expressed between AF patients and non-AF controls.MethodslEVs were isolated by differential centrifugation and characterized by Nanoparticle Tracking Analysis (NTA), Transmission Electron Microscopy (TEM), flow cytometry and Western blot analysis. For the discovery phase, 12 AF patients and 12 non-AF controls were enrolled to determine lEV-miRNA profile using quantitative reverse transcription polymerase chain reaction array. The candidate miRNAs were confirmed their expression in a validation cohort using droplet digital PCR (30 AF, 30 controls). Bioinformatics analysis was used to predict their target genes and functional pathways.ResultsTEM, NTA and flow cytometry demonstrated that lEVs presented as cup shape vesicles with a size ranging from 100 to 1000 nm. AF patients had significantly higher levels of lEVs at the size of 101-200 nm than non-AF controls. Western blot analysis was used to confirm EV markers and showed the high level of cardiomyocyte expression (Caveolin-3) in lEVs from AF patients. Nineteen miRNAs were significantly higher (> twofold, p < 0.05) in AF patients compared to non-AF controls. Six highly expressed miRNAs (miR-106b-3p, miR-590-5p, miR-339-3p, miR-378-3p, miR-328-3p, and miR-532-3p) were selected to confirm their expression. Logistic regression analysis showed that increases in the levels of these 6 highly expressed miRNAs associated with AF. The possible functional roles of these lEV-miRNAs may involve in arrhythmogenesis, cell apoptosis, cell proliferation, oxygen hemostasis, and structural remodeling in AF.ConclusionIncreased expression of six lEV-miRNAs reflects the pathophysiology of AF that may provide fundamental knowledge to develop the novel biomarkers for diagnosis or monitoring the patients with the high risk of AF.

Dataset Information

Increased small extracellular vesicle levels and decreased miR-126 levels associated with atrial fibrillation and coexisting diabetes mellitus.

Background

Hypothesis

Methods

Results

Conclusions

Publications

Increased small extracellular vesicle levels and decreased miR-126 levels associated with atrial fibrillation and coexisting diabetes mellitus.

Similar Datasets

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