Yanni, Joseph, D'Souza, Alicia, Wang, Yanwen, Li, Ning 
ORCID: 0000-0002-7595-3418, Hansen, Brian J, Zakharkin, Stanislav O ORCID: 0000-0001-9816-510X, Smith, Matthew ORCID: 0000-0002-4078-8352, Hayward, Christina ORCID: 0000-0003-3828-7126, Whitson, Bryan A ORCID: 0000-0003-0040-3638, Mohler, Peter J et al (show 18 more authors)
(2020)
Silencing miR-370-3p rescues funny current and sinus node function in heart failure.
Scientific reports, 10 (1).
11279 - ?.
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Abstract
Bradyarrhythmias are an important cause of mortality in heart failure and previous studies indicate a mechanistic role for electrical remodelling of the key pacemaking ion channel HCN4 in this process. Here we show that, in a mouse model of heart failure in which there is sinus bradycardia, there is upregulation of a microRNA (miR-370-3p), downregulation of the pacemaker ion channel, HCN4, and downregulation of the corresponding ionic current, If, in the sinus node. In vitro, exogenous miR-370-3p inhibits HCN4 mRNA and causes downregulation of HCN4 protein, downregulation of If, and bradycardia in the isolated sinus node. In vivo, intraperitoneal injection of an antimiR to miR-370-3p into heart failure mice silences miR-370-3p and restores HCN4 mRNA and protein and If in the sinus node and blunts the sinus bradycardia. In addition, it partially restores ventricular function and reduces mortality. This represents a novel approach to heart failure treatment.
| Item Type: | Article |
|---|---|
| Depositing User: | Symplectic Admin |
| Date Deposited: | 15 Jul 2020 09:22 |
| Last Modified: | 18 Jan 2023 23:45 |
| DOI: | 10.1038/s41598-020-67790-0 |
| Open Access URL: | https://www.nature.com/articles/s41598-020-67790-0 |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3094024 |
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- Silencing miR-370-3p rescues funny current and sinus node function in heart failure. (deposited 15 Jul 2020 09:22) [Currently Displayed]
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