Plasma extracellular vesicle proteomics identifies FN1/F13A1-TGF-β pathway as the major signaling pathway associated with persistent atrial fibrillation.

Atrial fibrillation (AF) is the most common arrhythmia worldwide. The prevalence of AF has increased over the past three decades. This study aimed to investigate the proteomic changes of plasma extracellular vesicles (EVs) in persistent AF (PEAF) and to better understand the role of EVs in the molecular mechanism of in AF. Plasma samples were prospectively collected from patients with PEAF and in sinus rhythm with negative coronary angiography. The patients were divided into 2 groups: PEAF and sinus rhythm (N = 22). In the first proteomics stage, liquid chromatography mass spectrometry (LC-MS) was used to detect differential proteins. In the second validation stage, the DEPs were validated in a new cohort of PEAF patients. The validated proteins were further analyzed by ROC. Among the 36 extracellular vesicle DEPs detected by the proteomics study, 3 (FN1, F13A1, and GP9) were successfully validated with AUC (area under curve) of more than 0.8 (p < 0.05). FN1 and F13A1 are involved in the TGF-β pathway. This study by using extracellular vesicle proteomics techniques identified specific extracellular vesicle proteins associated with AF in comparison to sinus rhythm. Our study suggests that in the plasma extracellular vesicle FN1/F13A1-TGF-β cell signaling pathway is linked with AF. FN1 and F13A1 have the potential to be further developed as specific potential plasma biomarkers for AF. The study reveals a novel mechanism for AF and provides new insights into new therapeutic targets for potential treatment of AF.