However, animal studies consistently support a causal role for IR in developing AF, likely through molecular pathways involving increased transforming growth factor beta-1 (TGF-β1), oxidative stress, Rac1 activation, and disrupted calcium handling mediated by oxidized calcium/calmodulin-dependent protein kinase type II delta (CaMKIIδ), all contributing to atrial remodeling and arrhythmogenesis [39]. This evidence concerns the gene TGFB1 and atrial fibrillation.