Abstract 11940: Mineralocorticoid Receptor Dysregulation by MicroRNA-135a in Bradycardic Arrhythmogenic Remodeling

Introduction: Complete atrioventricular block (CAVB) causes arrhythmogenic remodeling and increases the risk of Torsades de Pointes (TdP) arrhythmias. MicroRNAs (miRs) are key regulators of gene expression that contribute to cardiac remodeling. Here, we assess microRNA changes after CAVB and their potential significance in arrhythmogenic cardiac remodeling. Methods: CAVB was induced in mice via His bundle ablation. Expression of miRs was evaluated by pan-microRNA microarray with qPCR confirmation on samples from controls and at 24 hrs and 4 wks post-CAVB. Arrhythmias were detected by continuous monitoring. MicroRNA target prediction algorithms were used to identify potential target genes. Biological confirmation of targets was by luciferase assay and overexpression (OE) studies in HEK and H9c2 cells respectively. Results: TdP occurred within 24 hrs in 6/17 CAVB mice, vs no controls. Ventricular tachyarrhythmia episodes were frequent at 4 wks CAVB (212±83 per 24 hrs) and were not seen in controls. CAVB was...