Yanni, Joseph, D'Souza, Alicia, Wang, Yanwen, Li, Ning, Hansen, Brian J, Zakharkin, Stanislav O, Smith, Matthew, Hayward, Christina, Whitson, Bryan A, 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 |
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Uncontrolled Keywords: | Cardiac hypertrophy, Heart failure |
Depositing User: | Symplectic Admin |
Date Deposited: | 22 Jul 2020 11:22 |
Last Modified: | 18 Jan 2023 23:40 |
DOI: | 10.1038/s41598-020-67790-0 |
Related URLs: | |
URI: | https://livrepository.liverpool.ac.uk/id/eprint/3094870 |
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Silencing miR-370-3p rescues funny current and sinus node function in heart failure. (deposited 15 Jul 2020 09:22)
- Silencing miR-370-3p rescues funny current and sinus node function in heart failure. (deposited 22 Jul 2020 11:22) [Currently Displayed]