Different behaviour of NOX2 activation in patients with paroxysmal/persistent or permanent atrial fibrillation

Background NOX2, the catalytic subunit of NADPH oxidase, is suggested to play a role in favouring the occurrence of atrial fibrillation (AF) after cardiac surgery via formation of reactive oxidant species. However, its role in spontaneous AF is still unclear. Objective To define the role of NOX2 and isoprostanes, a marker of oxidative stress, in the different settings of AF. Methods The study was performed on 174 patients with AF (82 with paroxysmal/persistent AF and 92 with permanent AF) and 90 controls matched for sex, age and atherosclerotic risk factors. Urinary isoprostanes and serum levels of soluble NOX2-derived peptide (sNOX2-dp) were measured in each patient. Results Urinary isoprostanes and sNOX2-dp concentrations were significantly higher in patients with paroxysmal/persistent AF than in those with permanent AF and controls. Compared with controls, patients with permanent AF showed a weak increase in sNOX2-dp and no difference in isoprostanes. Multivariable analyses demonstrated that baseline values of sNOX2-dp and urinary isoprostanes were independently associated with the type of AF (paroxysmal/persistent vs permanent; beta=-224, p=0.007 and beta=-231, p=0.005, respectively). A significant correlation between sNOX2-dp levels and urinary excretion of isoprostanes was also detected (R=0.707, p<0.001). Conclusions This study provides evidence that NOX2 is upregulated only in patients with paroxysmal/persistent AF and is responsible for overproduction of isoprostanes. This finding warrants further study to see if inhibition of NOX2 may reduce the risk of paroxysmal/persistent AF.