Language

English

Publication Date

1-7-2026

Journal

Research Square

DOI

10.21203/rs.3.rs-8484728/v1

PMID

41542044

PMCID

PMC12803350

PubMedCentral® Posted Date

1-7-2026

PubMedCentral® Full Text Version

Pre-Print

Abstract

Atrial fibrillation (AF), the commonest cardiac arrhythmia, is a major contributor to mortality and morbidity. Atrial tissue fibrosis, a hallmark of structural remodelling in AF, is currently incurable and significantly hinders AF-treatment. MicroRNA(miR)-31 is linked to ageing (a key risk factor for AF). Here, we show that AF-patients are characterised by upregulation of miR-31–5p in atrial cardiofibroblasts that negatively regulates the calcitonin receptor (CTR), thereby promoting atrial fibrogenesis and arrhythmia. Specific blockade of miR-31–5p/CTR-mRNA binding with LNA-miRNA-Target-Site-Blocker selectively increases atrial CTR expression and reverses advanced atrial fibrosis and arrhythmogenesis in vivo. These findings suggest a key role for miR-31–5p/CTR binding in promoting atrial fibrosis and arrhythmogenesis, and represents a first example of an RNA-based therapeutic capable of reversing established fibrosis that forms an AF substrate.

Comments

Updated version available: A peer-reviewed version of this article, "Selective blockade of microRNA-31-5p-calcitonin receptor interaction reverses established atrial fibrosis and atrial arrhythmia burden.", has been published in Nat Cardiovasc Res.

Published Open-Access

yes

Download

Share

COinS
 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.