Selective blockade of microRNA-31-5p/calcitonin receptor interaction reverses established atrial fibrosis and atrial arrhythmia burden

MicroRNA-31-5p (miR-31-5p), an ageing-associated, atrial-enriched microRNA, has been linked to AF, but its role in atrial fibrosis is unknown. Here we show that atrial fibroblasts from patients with persistent AF exhibit increased miR-31-5p expression and reduced expression of the calcitonin receptor (CTR, encoded by CALCR).

MiR-31-5p directly represses CTR and promotes profibrotic fibroblast responses, whereas its inhibition restores CTR expression. Fibroblast-specific overexpression of miR-31 in mice reduces atrial CTR expression, increases atrial fibrosis and enhances arrhythmia susceptibility. Selective disruption of miR-31-5p/CALCR binding using a locked nucleic acid target-site blocker restores atrial CTR expression, prevents fibrosis progression and reduces arrhythmia burden.