In this study, several critical AF-associated pathways were highlighted, including extensive EF-mediated signals activated by ligands such as LAMININ and COLLAGEN, the AF-specific activation of MK (Midkine signaling) signaling, the absence of EC signals such as GRN–SORT1 (Progranulin-Sortilin 1) and AGRN–DAG1 (Agrin-Dystroglycan 1) in AF, and a marked reduction of the NPPA–NPR1 (Atrial Natriuretic Peptide-Guanylate Cyclase A) signal from SMC to EC. Here, NPPA is linked to atrial fibrillation.