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Updated: Apr 17, 2026

Estimating Bilateral Atrial Function by Cardiovascular Magnetic Resonance Feature Tracking in Patients with Paroxysmal Atrial Fibrillation
Published on: July 20, 2022
Identification of microRNA-mRNA dysregulations in paroxysmal atrial fibrillation
David Y Chiang1, Min Zhang2, Niels Voigt3
1Cardiovascular Research Institute, Baylor College of Medicine, Houston, TX, USA; Department of Molecular Physiology & Biophysics, Baylor College of Medicine, Houston, TX, USA.
Background:
The molecular mechanisms underlying the early development of atrial fibrillation (AF) remain poorly understood. Emerging evidence suggests that abnormal epigenetic modulation via microRNAs (miRNAs) might be involved in the pathogenesis of paroxysmal AF (pAF).
Objective:
To identify key molecular changes associated with pAF, we conducted state-of-the-art transcriptomic studies to identify the abnormal miRNA-mRNA interactions potentially driving AF development.
Methods:
High-quality total RNA including miRNA was isolated from atrial biopsies of age-matched and sex-matched pAF patients and control patients in sinus rhythm (SR; n=4 per group) and used for RNA-sequencing and miRNA microarray. Results were analyzed bioinformatically and validated using quantitative real-time (qRT)-PCR and 3'UTR luciferase reporter assays.
Results:
113 genes and 49 miRNAs were differentially expressed (DE) in pAF versus SR patients. Gene ontology analysis revealed that most of the DE genes were involved in the "gonadotropin releasing hormone receptor pathway" and "p53 pathway". Of these DE genes, bioinformatic analyses identified 23 pairs of putative miRNA-mRNA interactions that were altered in pAF (involving 15 miRNAs and 17 mRNAs). Using qRT-PCR and 3'UTR luciferase reporter assays, the interaction between upregulation of miR-199a-5p and downregulation of FKBP5 was confirmed in samples from pAF patients.
Conclusion:
Our combined transcriptomic analysis and miRNA microarray study of atrial samples from pAF patients revealed novel pathways and miRNA-mRNA regulations that may be relevant in the development of pAF. Future studies are required to investigate the potential involvement of the gonadotropin releasing hormone receptor and p53 pathways in AF pathogenesis.
Insights
This study reveals novel molecular pathways and microRNA-messenger RNA interactions involved in early atrial fibrillation (AF) development. Understanding these epigenetic changes, like miR-199a-5p and FKBP5, is key for future AF therapies.
Area of Science:
- Cardiovascular Biology
- Molecular Genetics
- Epigenetics
Background:
- The molecular basis of early atrial fibrillation (AF) development, particularly paroxysmal AF (pAF), is not fully understood.
- Emerging research suggests microRNAs (miRNAs) play a role in pAF pathogenesis through epigenetic modifications.
Purpose of the Study:
- To identify molecular alterations driving pAF by investigating abnormal miRNA-mRNA interactions.
- To uncover key molecular changes associated with the early stages of AF.
Main Methods:
- RNA sequencing and miRNA microarray analysis of atrial biopsies from pAF patients and sinus rhythm (SR) controls.
- Bioinformatic analysis to identify differentially expressed genes and miRNAs, and predict miRNA-mRNA interactions.
- Validation of predicted interactions using quantitative real-time PCR (qRT-PCR) and 3'UTR luciferase reporter assays.
Main Results:
- 113 genes and 49 miRNAs were differentially expressed between pAF and SR groups.
- Key pathways identified include the gonadotropin releasing hormone receptor and p53 pathways.
- Confirmed a specific interaction: upregulation of miR-199a-5p and downregulation of FKBP5 in pAF patients.
Conclusions:
- Combined transcriptomic and miRNA analysis identified novel pathways and miRNA-mRNA regulations potentially involved in pAF development.
- The gonadotropin releasing hormone receptor and p53 pathways warrant further investigation in AF pathogenesis.
- This study provides new insights into the molecular mechanisms underlying early AF.
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