Deciphering the Role of microRNAs: Unveiling Clinical Biomarkers and Therapeutic Avenues in Atrial Fibrillation and Associated Stroke—A Systematic Review
Abstract
:1. Introduction
1.1. Prevalence of Atrial Fibrillation and Ischemic Stroke
1.2. Pathophysiology and Prevention
1.3. miRNAs in Atrial Fibrillation and AIS
1.4. Aim of the Review
2. Methods
3. Results
3.1. Overview of All Described miRNAs
3.2. miRNA-1
3.2.1. miRNA-1 Heart
3.2.2. miRNA-1 Brain
3.3. miRNA-19
3.3.1. miRNA-19 Heart
3.3.2. miRNA-19 Brain
3.4. miRNA-21
3.4.1. miRNA-21 Heart
3.4.2. miRNA-21 Brain
3.5. miRNA-145
3.5.1. miRNA-145 Heart
3.5.2. miRNA-145 Brain
3.6. miRNA-146a Heart and Brain
4. Outlook and Conclusions
4.1. Outlook
- Targeting miRNA-1 with an antagomir, which is a chemically engineered oligonucleotide designed to silence specific miRNAs, may stabilize cardiac membrane potentials and rhythmological conditions while reducing apoptotic mechanisms in the brain, thus preventing neuroptosis.
- Lowering the plasma level of miRNA-19 by antagomir would decrease oxidative stress and neuroinflammation in the brain and stabilize the rhythmological situation in the heart, but make cardiomyocytes more susceptible to controlled cell death.
- Similarly, the use of an agomir of miRNA-146, which is a synthetic miRNA mimic that enhances the activity of specific miRNAs, can reduce induced inflammation/coagulation in the heart and neuroinflammation in the brain simultaneously.
- An agomir of miRNA-145, for example, could further enhance the beneficial effect in the brain with reduced edema formation due to reduced transmembrane incorporation of aquaporin 4, whereas in the heart it induces more balanced calcium homeostasis with improved rhythmic control.
- Only miRNA-21 acts oppositely on the heart and brain with respect to drug therapy regimens, as lowering miRNA-21 levels would prevent increased collagen formation and thus fibrosis of the cardiac situation, but in the brain it would increase the apoptotic tendency of astrocytes in the event of an AIS.
4.2. Potential Research Scenarios
- Validation and Mechanistic Studies: Conducting extensive in vitro and in vivo studies to validate the molecular mechanisms and therapeutic potential of specific miRNAs in AF and AIS. This involves creating animal models to observe the effects of miRNA modulation on cardiac and brain tissues, focusing on pathways related to inflammation, apoptosis and cellular homeostasis.
- Drug Development and Delivery: Developing miRNA-based drugs such as antagomirs and agomirs and refining their delivery systems to ensure targeted and efficient treatment with minimal off-target effects. This includes exploring nanoparticle-based delivery methods and assessing the pharmacokinetics and pharmacodynamics of these miRNA therapeutics.
- Clinical Trials: Initiating phase I and II clinical trials to evaluate the safety, dosage and preliminary efficacy of miRNA-based therapies in humans. These trials would provide critical data on how these therapies perform in real-world scenarios and help refine therapeutic strategies.
- Interdisciplinary Research: Fostering collaboration between molecular biologists, cardiologists, neurologists and pharmacologists to integrate findings from basic research with clinical insights. This interdisciplinary approach is crucial for developing comprehensive treatment protocols and ensuring that laboratory discoveries translate effectively into clinical practice.
- Personalized Medicine: Investigating the role of miRNAs in personalized medicine by identifying miRNA profiles that predict patient responses to treatment. This could lead to the development of personalized therapeutic regimens that optimize efficacy and minimize adverse effects based on an individual’s miRNA expression patterns.
4.3. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Authors | Year | Study | miRNA | Major Outcomes |
---|---|---|---|---|
Arroyo et al. [45] | 2018 | Human | miR-146a | miR-146a
|
Benito et al. [46] | 2022 | Human | miR-1-3p | miR-1-3p
|
Chen et al. [47] | 2018 | Human | miR-15a-5p miR-17-5p miR-19b-3p miR-20a-5p | miR-15a-5p, miR-17-5p, miR-19b-3p, miR-20a-5p
|
Kim et al. [48] | 2022 | Human | miR-93-5p miR-378f miR-450b-5p miR-629-5p | miR-378f, miR-450b-5p
miR-93-5p, miR-629-5p
|
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Boxhammer, E.; Dienhart, C.; Rezar, R.; Hoppe, U.C.; Lichtenauer, M. Deciphering the Role of microRNAs: Unveiling Clinical Biomarkers and Therapeutic Avenues in Atrial Fibrillation and Associated Stroke—A Systematic Review. Int. J. Mol. Sci. 2024, 25, 5568. https://doi.org/10.3390/ijms25105568
Boxhammer E, Dienhart C, Rezar R, Hoppe UC, Lichtenauer M. Deciphering the Role of microRNAs: Unveiling Clinical Biomarkers and Therapeutic Avenues in Atrial Fibrillation and Associated Stroke—A Systematic Review. International Journal of Molecular Sciences. 2024; 25(10):5568. https://doi.org/10.3390/ijms25105568
Chicago/Turabian StyleBoxhammer, Elke, Christiane Dienhart, Richard Rezar, Uta C. Hoppe, and Michael Lichtenauer. 2024. "Deciphering the Role of microRNAs: Unveiling Clinical Biomarkers and Therapeutic Avenues in Atrial Fibrillation and Associated Stroke—A Systematic Review" International Journal of Molecular Sciences 25, no. 10: 5568. https://doi.org/10.3390/ijms25105568