MicroRNAs in Atrial Fibrillation: Mechanisms, Vascular Implications, and Therapeutic Potential
Abstract
:1. Introduction
2. MicroRNA-Mediated Fibrotic Mechanisms in Atrial Fibrillation
- Disruption of atrial conduction: Fibrosis can modify the electrical and mechanical properties of the atrial tissue, contributing to the initiation and maintenance of the arrhythmia. One of the key mechanisms through which fibrosis exerts its effect is by disrupting atrial conduction. Fibrosis can create regions of slowed conduction, a conduction block, and conduction heterogeneity in the atrial tissue, which promotes the formation of re-entrant circuits that sustain AFib. The underlying mechanism for this effect is thought to be related to the increased interstitial resistance and reduced intercellular coupling caused by fibrosis. In fibrotic tissue, the gap junctions that allow for rapid cell-to-cell communication become disrupted, leading to a decrease in the velocity and uniformity of the electrical signal propagation. This, in turn, can create areas of slow or blocked conduction that serve as the substrate for the formation of re-entrant circuits, which sustain AFib [3].
- Enhancement of automaticity: Fibrosis can facilitate the emergence of ectopic foci in the atrial tissue by modifying the electrophysiological characteristics of the cardiomyocytes. In particular, fibrosis can induce alterations in the ion channels and calcium handling proteins that govern the generation and propagation of action potentials in the atrial myocytes. These modifications can enhance the automaticity of the cardiomyocytes, rendering them more susceptible to generating spontaneous impulses that give rise to ectopic foci capable of triggering Afib [4].
- Alteration of repolarization: Fibrosis can modify the repolarization properties of the atrial myocytes, resulting in an elongation of the action potential duration and a heterogeneity of repolarization across the atrial tissue. These changes can produce a substrate that promotes the development of arrhythmias by facilitating the formation of re-entrant circuits and ectopic foci. Moreover, fibrosis can increase the susceptibility of the atrial tissue to the effects of triggers, such as adrenergic stimulation or rapid pacing, by altering the electrophysiological properties of the cells. Consequently, these triggers can more readily cause disruptions in the conduction of electrical impulses across the atrial tissue, potentially leading to the onset or perpetuation of Afib [5].
- Mechanical stiffness and stretch-induced remodeling: Fibrosis can modify the mechanical properties of the atrial tissue, reducing its compliance and increasing its susceptibility to stretch-induced remodeling. This can predispose the tissue to atrial dilatation and hypertension, both of which are established risk factors for atrial fibrillation. Additionally, fibrosis can instigate a pro-inflammatory and pro-fibrotic milieu within the atrial tissue, amplifying the fibrotic process and fueling the development of Afib [6].
3. MicroRNAs in Atrial Fibrillation’s Inflammatory Pathways
4. Oxidative Stress and MicroRNA Interplay in Atrial Fibrillation
5. MicroRNAs and Their Vascular Implications in Atrial Fibrillation
6. MicroRNAs as Emerging Biomarkers and Therapeutic Facilitators of Atrial Fibrillation; Future Perspectives
6.1. miRNAs as Potential Biomarkers of Atrial Fibrillation
6.2. miRNAs as Biomarkers of the Risk of Major Adverse Thrombotic Cardiovascular Events in Atrial Fibrillation
6.3. miRNAs as Potential Therapeutic Agents in Atrial Fibrillation Management
7. Conclusions
Funding
Conflicts of Interest
References
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miRNA | Target Genes/Pathways |
---|---|
miR-146b-5p | TIMP4, MMP9, TGFB1, COL1A1 |
miR-210-3p | GPD1L, PI3K/AKT pathway |
miR-29, miR-30, miR-133, miR-21 | Connective tissue growth factor (CTGF) |
miR-23b-3p, miR-27b-3p | COL1A1, COL3A1, ACTA2 TGFBR3/Smad3 pathway |
miR-128-3p | PVT1, Sp1 TGF-β1/Smad pathway |
miR-26 | CNJ2/IK TRPC3 |
miR-181b | Sema3A Sema3A/LIMK/p-cofilin/actin axis |
miRNA | Target Genes/Pathways | Role in Inflammation |
---|---|---|
miR-146a | TLR4, IRAK1, TRAF6 NF-κB pathway | Negative regulator of innate inflammatory responses NET formation |
miR-21 | STAT3 pathway | Promotes inflammation-associated fibrosis |
miR-355, miR-26b | GATA4 | Alters fibroblast expression (cellular senescence) Affects atrial conduction through calcium homeostasis |
miR-150 | TGF-β EGRR2, P2X7R | Modulates inflammatory response system by targeting pro-inflammatory ATP receptor and multiple regulatory genes |
miR-222 | Associated with DVHD P27 ICAM-1 | Role in inflammation-mediated vascular remodeling Downregulation of IRF-2 |
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Vardas, E.P.; Theofilis, P.; Oikonomou, E.; Vardas, P.E.; Tousoulis, D. MicroRNAs in Atrial Fibrillation: Mechanisms, Vascular Implications, and Therapeutic Potential. Biomedicines 2024, 12, 811. https://doi.org/10.3390/biomedicines12040811
Vardas EP, Theofilis P, Oikonomou E, Vardas PE, Tousoulis D. MicroRNAs in Atrial Fibrillation: Mechanisms, Vascular Implications, and Therapeutic Potential. Biomedicines. 2024; 12(4):811. https://doi.org/10.3390/biomedicines12040811
Chicago/Turabian StyleVardas, Emmanouil P., Panagiotis Theofilis, Evangelos Oikonomou, Panos E. Vardas, and Dimitris Tousoulis. 2024. "MicroRNAs in Atrial Fibrillation: Mechanisms, Vascular Implications, and Therapeutic Potential" Biomedicines 12, no. 4: 811. https://doi.org/10.3390/biomedicines12040811
APA StyleVardas, E. P., Theofilis, P., Oikonomou, E., Vardas, P. E., & Tousoulis, D. (2024). MicroRNAs in Atrial Fibrillation: Mechanisms, Vascular Implications, and Therapeutic Potential. Biomedicines, 12(4), 811. https://doi.org/10.3390/biomedicines12040811