miR-144-3p and miR-425-5p are Negatively Associated With Atrial Fibrosis and Promote Atrial Remodeling by Targeting CREB1 in Atrial Fibrillation

Background: Progression of atrial fibrosis is vital for atrial remodeling in atrial fibrillation (AF). The main objective of this study was to explore the association between miR-144-3p and miR-425-5p, and atrial fibrosis as well as the resultant impact on atrial remodeling in AF.Methods and Results: Through miRNAs sequencing and qRT-PCR, we demonstrated that miR-144-3p and miR-425-5p were downregulated in plasma and atrial tissue among the patients who suffered from AF. We confirmed that the plasma’s miRNAs level was negatively correlated with left atrial fibrosis, which was evaluated with the left low voltage area using left atrial voltage matrix mapping. Catheter ablation restored decreased plasma miR-144-3p and miR-425-5p. Besides, ROC curve analysis revealed that the miRNAs not only differentiated AF from healthy control of AUC 0.928 and 0.921, respectively, but also discriminated persistent AF from paroxysmal AF of AUC 0.906 and 0.888, respectively. Furthermore, the downregulated miR-144-3p and miR-425-5p promoted atrial fibroblast proliferation by CCK-8. CREB1 was realized to be a common direct target for miR-144-3p and miR-425-5p by western blot and luciferase assay.Conclusions: Our findings suggested that miR-144-3p and miR-425-5p could serve as novel atrial fibrosis biomarkers and hence contribute to atrial remodeling in AF.