Proteomic profiles of patients with atrial fibrillation provide candidate biomarkers for diagnosis

Background: Atrial fibrillation (AF) is the most common cardiac arrhythmia worldwide with an increasing risk of heart failure, stroke, and thromboembolic events. Currently distinct pathophysiological mechanisms during AF development and valuable biomarkers for AF management remain unknown. Methods: In this study, we collected peripheral plasma samples from 18 non-valvular AF patients and 10 controls. A LC-MS/MS-DIA-based quantitative proteomic analysis, as well as bioinformatic analysis, was performed for discovery of differentially expressed proteins (DEPs) and dysregulated pathways. Next, we utilized enzymelinked immunosorbent assay (ELISA) to validate selected DEPs and assessed their abilities for discrimination in another group of 20 AF patients and 10 controls. Results: The plasma proteome provided evidence for vital roles of abnormal inflammation, hemostasis, tissue remodeling and metabolism in AF patients. Differences between paroxysmal and persistent AF mainly lie in proteins or pathways related to hemostasis and cardiac remodeling. In addition, we successfully validated upregulated proteins of platelet factor 4 variant 1 (PF4V1), thrombospondin-1 (THBS1), platelet basic protein (PBP) and fructose-bisphosphate aldolase A (ALDOA) in another group, which could make discrimination between AF patients and controls. Conclusions: Our pilot proteomic study provided candidate biomarkers of PF4V1, THBS1, PBP and ALODA with the hope of application in AF management. And we showed the differences in pathophysiological mechanisms between paroxysmal and persistent AF. They mainly focused on pathways of hemostasis and cardiac remodeling, which could be a valuable clue for further research on AF progression.