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; β=-224, p=0.007 and β=-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.
Clinica Medica, Sapienza University of Rome, Viale del Policlinico 155, Roma 00161, Italy.
Roberto
R
Cangemi
Andrea
A
Celestini
Camilla
C
Calvieri
Roberto
R
Carnevale
Daniele
D
Pastori
Cristina
C
Nocella
Tommasa
T
Vicario
Pasquale
P
Pignatelli
Francesco
F
Violi
D000368:Aged; D001281:Atrial Fibrillation / Q000201:enzymology*; D015415:Biomarkers / Q000097:blood; D004789:Enzyme Activation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000096:biosynthesis*; D018384:Oxidative Stress; D011379:Prognosis; D012189:Retrospective Studies; D013614:Tachycardia, Paroxysmal / Q000201:enzymology*
D015415:Biomarkers; D008562:Membrane Glycoproteins; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases