Vascular endothelial barrier protection prevents nanoscale cardiac remodeling: a novel strategy to prevent atrial fibrillation

Abstract

Atrial fibrillation (AF) patients experience inflammation and vascular dysfunction and have elevated levels of cytokines that promote vascular leak and edema, such as vascular endothelial growth factor (VEGF). We previously identified edema-induced disruption of sodium channel (NaV1.5) -rich intercalated disk (ID) nanodomains as a novel arrhythmia mechanism. Therefore, we hypothesized that: (i) VEGF-induced vascular leak acutely slows action potential propagation in the atria and increases arrhythmia risk by disrupting ID nanodomains, and (ii) protection of the vascular barrier can prevent vascular leak-induced atrial arrhythmias.