Control of Atrial Remodeling by miRNA Modulation as an Additive Strategy in Surgical Atrial Fibrillation Ablation

Objectives: The extent of remodeling determines both re-initiation and perpetuation of atrial fibrillation after surgical ablation. In contrast to the intentional scarring of ablation lines, antifibrotic remodeling should ensure therapeutic success. Antifibrotic miR-133a is a specific microRNA of the heart and skeletal muscle, which is associated with the regulation of atrial remodeling.

Methods: Primary human atrial cardiofibroblasts from patients undergoing cardiac surgery with (atrial fibrillation) or without (sinus rhythm) surgical ablation were isolated. Expression profiles from pro- and antifibrotic miRNAs and the functional consequence of the modification of these were analyzed.

Result: Atrial fibrillation and the persistence of the arrhythmia results in progressive deterioration of pro- and antifibrotic miRNA profiles, atrial fibrosis and the occurrence of atrial fibrillation correlate in atrial tissue and primary cells regarding pro- and antifibrotic miRNAs. miR-199a-5p, miR-21–5p, and miR-216a-5p were significantly higher in persistent AF than in paroxysmal AF. miR-208a-3p was comparably increased in both AF patients groups. miR-217 was only increased in persistent AF patients. Anti-fibrotic miRNAs (miR-133a, -26a-5p, and 29b-3p) were significantly different between paroxysmal AF than in persistent AF patients with lowest level in persistent atrial fibrillation. Overexpression of miR-133a in cardiac fibroblasts inhibited the mRNA-expression of fibrosis-associated genes for connective tissue growth factor (CTGF) and collagens I and III. Modification of cell proliferation and their differentiation into myofibroblasts is dependent on miR-expression and can be promoted or prevented.

Conclusion: miRNA-133a is dysregulated during atrial fibrillation. miR-133a expression might be used as a prognostic marker as well as a potential additive target to optimize long-term therapeutic success after primary scarification of ablation lines by reducing structural remodeling.

Publication History

Article published online:
19 February 2021