NOX4-Dependent Hydrogen Peroxide Overproduction in Human Atrial Fibrillation and HL-1 Atrial Cells: Relationship to Hypertension.
OBJECTIVE
Atrial fibrillation (AF) is the most common type of cardiac arrhythmia with patients dying frequently of stroke. In view of the unclear etiologies of AF and a potential role of oxidative stress, the present study examined cardiac reactive oxygen species production and NADPH oxidase (NOX) expression in AF patients.


RESULTS
Patients with AF were older than those without (58.8 ± 11.7 vs. 47.8 ± 19.2, p = 0.047). Whereas total [Formula: see text] production (determined by electron spin resonance) was similar in patients with and without AF, H(2)O(2) production was more than doubled in AF patients (149.8 ± 26.28 vs. 66.9 ± 7.14 pmol/mg/min, p = 0.0055), which correlated well with a doubling in NOX isoform 4 (NOX4) expression. AF patients with co-existing hypertension had three-fold higher H(2)O(2) production compared to those without (239.0 ± 125.1 vs. 83.6 ± 51.3 pmol/mg/min, p = 0.003). Treatment of HL-1 atrial cells with angiotensin II, a known modulator of atrial structural remodeling, resulted in upregulation of NOX4 and H(2)O(2) production, further implicating a potential role of NOX4 in atrial remodeling.


CONCLUSIONS
Our data represent the first implication that NOX4-derived H(2)O(2) may play an important role in the etiologies of AF.
Division of Molecular Medicine, Cardiovascular Research Laboratories, Department of Anesthesiology, David Geffen School of Medicine at University of California Los Angeles Los Angeles, CA, USA.
Jun
J
Zhang
Ji Youn
JY
Youn
Antony Y
AY
Kim
Rafael J
RJ
Ramirez
Ling
L
Gao
Doan
D
Ngo
Peng
P
Chen
Jennifer
J
Scovotti
Aman
A
Mahajan
Hua
H
Cai