Although NOS uncoupling, possibly of both eNOS and inducible NOS, has been shown in several studies,32,44,45 there is recent evidence for loss of nNOS in the RAA of patients with permanent AF, which could be recovered by prevention of miR-31 binding to the nNOS 3′-UTR.46 Interestingly, selective inhibition of nNOS in atrial myocytes isolated from patients in sinus rhythm (SR) mimicked the action potential (AP) shortening observed in AF, but had no effect in atrial myocytes isolated from patients with AF. This evidence concerns the gene NOS2 and atrial fibrillation.