Functional analysis revealed that the 6 highly expressed lEV-miRNA targets may involve in AF pathophysiology, including cardiac signaling pathway (adrenergic signaling in cardiomyocytes, arrhythmogenic right ventricular cardiomyopathy), cell proliferation (Hippo signaling pathway, PI3K-Akt signaling pathway), cell apoptosis (p53 signaling pathway), oxygen homeostasis (HIF-1 signaling pathway), and structural remodeling (Focal adhesion, ECM-receptor interaction) (Fig. 6D). The gene discussed is TP53; the disease is atrial fibrillation.