Silencing miR-370-3p rescues funny current and sinus node function in heart failure.
Sci Rep
; 10(1): 11279, 2020 07 09.
Article
em En
| MEDLINE
| ID: mdl-32647133
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Nó Sinoatrial
/
Inativação Gênica
/
MicroRNAs
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Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização
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Insuficiência Cardíaca
Limite:
Animals
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Humans
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Male
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article