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Silencing miR-370-3p rescues funny current and sinus node function in heart failure
Joseph Yanni1, Alicia D'Souza1, Yanwen Wang1
1Division of Cardiovascular Sciences, University of Manchester, 46 Grafton Street, Manchester, M13 9NT, UK.
Scientific Reports
|July 11, 2020
Summary
MicroRNA miR-370-3p causes bradycardia in heart failure by downregulating the HCN4 channel. Inhibiting miR-370-3p restores channel function, improves heart function, and reduces mortality in mice.
Area of Science:
- Cardiology
- Molecular Biology
- Genetics
Background:
- Bradyarrhythmias are a significant cause of mortality in heart failure.
- Electrical remodeling of the HCN4 pacemaker channel is implicated in this process.
Purpose of the Study:
- To investigate the role of microRNA miR-370-3p in heart failure-induced bradycardia.
- To explore the therapeutic potential of targeting miR-370-3p for heart failure treatment.
Main Methods:
- Utilized a mouse model of heart failure exhibiting sinus bradycardia.
- Investigated the effects of miR-370-3p on HCN4 expression and function in vitro and in vivo.
- Administered an antimiR to miR-370-3p in heart failure mice.
Main Results:
- Heart failure mice showed increased miR-370-3p, decreased HCN4, and reduced If current.
- Exogenous miR-370-3p inhibited HCN4 and caused bradycardia in isolated sinus nodes.
- AntimiR treatment restored HCN4, If, blunted bradycardia, improved ventricular function, and reduced mortality.
Conclusions:
- miR-370-3p plays a key role in heart failure-related bradycardia by targeting HCN4.
- Inhibition of miR-370-3p offers a novel therapeutic strategy for heart failure.
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