miRNA101a secreted by EATMs regulates atrial fibrillation through the PDGF-mediated PI3K/AKT pathway

Background Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia worldwide, and microRNAs (miRNAs) are gaining significant attention in cardiovascular disease research. In this study, we explored the specific mechanisms by which miR101a contributes to the pathogenesis of AF, aiming to identify a novel biomarker for its early detection. Methods In this study, we examined the differential expression of miR101a in human left atrial appendage tissue using RT-PCR. We developed a Sprague-Dawley rat model of AF and assessed the expression of associated phenotypic markers and proteins through flow cytometry, immunofluorescence, and Western blotting. Potential targets were identified via bioinformatics analysis and dual luciferase assay. We modulated miR101a expression using adenoviral transfection to elucidate its regulatory mechanism in AF. This approach allowed us to identify and validate the pathway through which miR101a influences AF. Results The experimental results indicated that miR101a was highly expressed in the sinus rhythm group of patients and played a crucial role in the myofibrosis associated with AF. miR101a interacted with PDGF-DD, contributing to fibroblast fibrosis, and modulated the fibrotic process by promoting the degradation of collagen and extracellular matrix in AF. In vivo animal experiments demonstrated a protective role of miR101a in the progression of AF. Furthermore, the findings revealed that the PI3K-Akt pathway was activated in AF, and miR101a was capable of modulating AF progression through this pathway. Conclusion In this study, we demonstrated that miR101a, secreted by epicardial adipose macrophage-derived exosomes, regulates AF via the PI3K-Akt pathway and by targeting PDGF-DD. These findings suggest that miR101a holds promise as a novel biomarker for AF.