Immune responses and activity of inflammatory mediators in pulmonary vein arrhythmogenesis

Atrial fibrillation (AF) is the most common type of sustained arrhythmia with potentially serious complications and risk of mortality. Inflammation plays an indispensable role in the pathogenesis of AF, evidenced by the elevated levels of various cytokines such as C-reactive protein, macrophage migration inhibitor (MIF), interleukin-6 (Il-6), and tumor necrosis factor-α (TNF-α). Pulmonary veins (PVs) are the main site of AF initiation, where cells acquire arrhythmogenic properties under the effects of pro-inflammatory mediators. Calcium/calmodulin-dependent protein kinase II (CaMKII) signaling also plays a critical role in arrhythmogenesis, which is modulated by aberrant Ca2+ homeostasis and ion currents, as well as the electrophysiological properties of PVs influenced by inflammatory mediators, including MIF. Today, pulmonary vein isolation (PVI) is one of the main treatments for AF. This review aimed to outline our current understanding of the underlying mechanisms of AF in an effort to open a new window for discovering novel therapies for this type of arrhythmia.