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MicroRNA-365 regulates human cardiac action potential duration
Dena Esfandyari1,2, Bio Maria Ghéo Idrissou1,2, Konstantin Hennis3
1Institute of Pharmacology and Toxicology, Technical University of Munich (TUM), 80802, Munich, Germany.
Nature Communications
|January 12, 2022
Summary
MicroRNA miR-365 regulates cardiac action potential duration by targeting key repolarization channels. Modulating miR-365 offers potential therapeutic strategies for cardiac arrhythmias like Long-QT and Short-QT syndromes.
Area of Science:
- Cardiology
- Molecular Biology
- Genetics
Background:
- Abnormalities in ventricular action potential lead to life-threatening cardiac arrhythmias and sudden cardiac death.
- MicroRNAs (miRNAs) are critical regulators of gene expression with potential roles in cardiac electrophysiology.
Purpose of the Study:
- To identify specific microRNAs that regulate the human cardiac action potential.
- To investigate the therapeutic potential of manipulating microRNAs for correcting action potential abnormalities.
Main Methods:
- Quantitative analysis of microRNA targetomes in human cardiac myocytes.
- Action potential recordings in patient-specific induced pluripotent stem cell-derived cardiac myocytes.
- Transcriptome analyses (bulk and single-cell), whole-cell patch-clamp, and human myocardial slice experiments.
Main Results:
- miR-365 was identified as a key regulator of cardiac repolarizing ion channels.
- Elevating miR-365 prolonged action potential duration in Short-QT syndrome myocytes.
- Inhibiting miR-365 normalized action potential duration in Long-QT syndrome myocytes.
- miR-365 directly targets cardiac repolarizing channels and synergistically regulates other action potential genes.
Conclusions:
- miR-365 plays a crucial role in regulating human cardiac action potential duration.
- Targeting miR-365 presents a promising therapeutic avenue for managing cardiac arrhythmias associated with action potential abnormalities.
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