Blocking microRNA-31-5p interaction reverses heart scarring and atrial fibrillation in study

A study led by Baylor College of Medicine and the University of Oxford, published in Nature Cardiovascular Research on October 30, 2026, reveals that blocking microRNA-31-5p interaction with calcitonin receptor mRNA restores receptor levels and reverses structural heart scarring. In mouse models and human cellular models of persistent atrial fibrillation, target-site blocker therapy regressed established atrial fibrosis by approximately 30% and reduced arrhythmia burden, addressing a major unmet gap in cardiovascular medicine.

Target-site blocker therapeutic effects

• ▪Treatment with a selective target-site blocker preventing microRNA-31-5p from binding calcitonin receptor mRNA restored calcitonin receptor protein levels in human atrial fibroblasts and mouse models.
• ▪Selective target-site blocker blockade of the microRNA-31-5p interaction with calcitonin receptor mRNA significantly reduced the duration and burden of atrial arrhythmias in mouse models.
• ▪Target-site blocker treatment targeting microRNA-31-5p reversed established atrial fibrosis in mouse models, regressing scar tissue by approximately 30% relative to baseline while untreated controls progressed.

MicroRNA-31-5p regulation of calcitonin receptors

• ▪A study led by researchers at Baylor College of Medicine and the University of Oxford, published in Nature Cardiovascular Research on October 30, 2026, identified microRNA-31-5p as an upstream regulator of calcitonin receptor abundance.
• ▪Genetically induced overexpression of microRNA-31-5p in mouse cardiac fibroblasts significantly reduced atrial calcitonin receptor protein without altering heart rate or ventricular function.

Calcitonin pathway dysregulation in atrial fibrillation

• ▪Cardiac calcitonin produced by atrial cardiomyocytes acts in a paracrine manner via calcitonin receptors on neighboring atrial fibroblasts to limit fibroblast activation and structural fibrosis.
• ▪Patients with persistent atrial fibrillation lasting longer than seven days exhibit six-fold lower atrial calcitonin production, reduced calcitonin receptor protein expression, and increased receptor internalization.

MicroRNA-31-5p effects on cardiofibroblasts

• ▪In vitro overexpression of microRNA-31-5p in sinus rhythm human atrial cardiofibroblasts increased collagen-1 accumulation by approximately 30% and boosted cell proliferation by 50%.
• ▪Inhibition of microRNA-31-5p in human atrial cardiofibroblasts from persistent atrial fibrillation patients halved collagen-1 content and reduced cell proliferation by approximately 29%.
• ▪Human atrial cardiofibroblasts from patients with atrial fibrillation produce twice the amount of microRNA-31-5p compared to non-fibrillating sinus rhythm cells.
• ▪Inhibition of microRNA-31-5p reduced fibronectin protein levels in human atrial fibroblasts isolated from patients with persistent atrial fibrillation.

Atrial fibrillation burden and treatment limitations

• ▪Existing therapies like anti-arrhythmic drugs, cardioversion, and catheter ablation treat electrical arrhythmia symptoms but fail to directly halt or reverse structural atrial fibrosis.
• ▪Atrial fibrillation affects over 10 million adults in the United States and causes 30% to 40% of all strokes, while increasing risks of heart failure, myocardial infarction, dementia, and kidney disease.