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Circulating miRNAs in acute new-onset atrial fibrillation and their target mRNA network
Ananília Medeiros Gomes da Silva1, Jéssica Nayara Góes de Araújo1, Katiene Macêdo de Oliveira1
1Department of Clinical Analysis and Toxicology, Federal University of Rio Grande do Norte, Natal, RN, Brazil.
Background:
MicroRNAs (miRNAs) are involved in the pathogenesis of atrial fibrillation (AF), acting on development and progression. Our pilot study investigated the expression of six miRNAs and their miRNA-mRNA interactions in patients with acute new-onset AF, well-controlled AF, and normal sinus rhythm (controls).
Methods And Results:
Plasma of acute new-onset AF patients (n = 5) was collected in the emergency room when patients presented with irregular and fast-atrial fibrillation rhythm. Samples from well-controlled AF (n = 16) and control (n = 15) patients were collected during medical appointments following an ECG. Expression of miR-21, miR-133a, miR-133b, miR-150, miR-328, and miR-499 was analyzed by real-time PCR. Ingenuity Pathway Analysis and the TargetScan database identified the top 30 mRNA targets of these miRNA, seeking the miRNA-mRNA interactions in cardiovascular process. Increased expression of miR-133b (1.4-fold), miR-328 (2.0-fold), and miR-499 (2.3-fold) was observed in patients with acute new-onset AF, compared with well-controlled AF and control patients. Decreased expression of miR-21 was seen in patients with well-controlled AF compared to those with acute new-onset AF and controls (0.6-fold). The miRNA-mRNA interaction demonstrated that SMAD7 and FASLG genes were the targets of miR-21, miR-133b, and miR-499 and were directly related to AF, being involved in apoptosis and fibrosis.
Conclusion:
The miRNAs had different expression profiles dependent on the AF condition, with higher expression in the acute new-onset AF than well-controlled AF. Clinically, this may contribute to an effective assessment for patients, leading to early detection of AF and monitoring to reduce the risk of other serious cardiovascular events.
Insights
MicroRNAs (miRNAs) show distinct expression patterns in atrial fibrillation (AF). Specific miRNAs like miR-133b, miR-328, and miR-499 are upregulated in acute new-onset AF, potentially aiding early detection.
Area of Science:
- Molecular biology
- Cardiovascular research
- Biomarker discovery
Background:
- MicroRNAs (miRNAs) play a role in the development and progression of atrial fibrillation (AF).
- Understanding miRNA expression profiles can offer insights into AF pathogenesis.
- This pilot study examines specific miRNAs and their mRNA targets in different AF states.
Purpose of the Study:
- To investigate the differential expression of six selected miRNAs in patients with acute new-onset AF, well-controlled AF, and normal sinus rhythm.
- To identify miRNA-mRNA interactions relevant to cardiovascular processes, particularly in AF.
- To explore the potential clinical utility of these miRNAs as biomarkers for AF.
Main Methods:
- Plasma samples were collected from patients with acute new-onset AF (n=5), well-controlled AF (n=16), and controls (n=15).
- Real-time PCR was used to analyze the expression levels of miR-21, miR-133a, miR-133b, miR-150, miR-328, and miR-499.
- Ingenuity Pathway Analysis and TargetScan were employed to predict miRNA-mRNA interactions, focusing on cardiovascular pathways.
Main Results:
- Increased expression of miR-133b (1.4-fold), miR-328 (2.0-fold), and miR-499 (2.3-fold) was observed in acute new-onset AF patients compared to controls.
- Decreased expression of miR-21 (0.6-fold) was noted in well-controlled AF patients relative to acute new-onset AF and control groups.
- SMAD7 and FASLG were identified as key mRNA targets of miR-21, miR-133b, and miR-499, implicated in apoptosis and fibrosis relevant to AF.
Conclusions:
- Distinct miRNA expression profiles correlate with different atrial fibrillation conditions.
- Upregulated miR-133b, miR-328, and miR-499 in acute AF suggest their involvement in the condition's pathogenesis.
- These miRNAs may serve as valuable biomarkers for early AF detection and risk stratification, potentially reducing cardiovascular event risk.
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