AUTHOR=Zhang Jun , Youn Ji Youn , Kim Antony , Ramire Rafael , Gao Ling , Ngo Doan , Scovotti Jennifer , Mahajan Aman , Cai Hua L.

TITLE=NOX4-Dependent Hydrogen Peroxide Overproduction in Human Atrial Fibrillation and HL-1 Atrial Cells: Relationship to Hypertension

JOURNAL=Frontiers in Physiology

VOLUME=3

YEAR=2012

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2012.00140

DOI=10.3389/fphys.2012.00140

ISSN=1664-042X

ABSTRACT=<p><bold>Background/Objectives:</bold> 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. <bold>Methods and Results:</bold> Patients with AF were older than those without (58.8 ± 11.7 vs. 47.8 ± 19.2, <italic>p</italic> = 0.047). Whereas total <inline-formula><mml:math id="M1" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:msubsup><mml:mrow><mml:mstyle class="text"><mml:mtext>O</mml:mtext></mml:mstyle></mml:mrow><mml:mrow><mml:mstyle class="text"><mml:mtext>2</mml:mtext></mml:mstyle></mml:mrow><mml:mrow><mml:mo class="MathClass-bin">∙</mml:mo><mml:mo class="MathClass-bin">-</mml:mo></mml:mrow></mml:msubsup></mml:mrow></mml:math></inline-formula> production (determined by electron spin resonance) was similar in patients with and without AF, H<sub>2</sub>O<sub>2</sub> production was more than doubled in AF patients (149.8 ± 26.28 vs. 66.9 ± 7.14 pmol/mg/min, <italic>p</italic> = 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<sub>2</sub>O<sub>2</sub> production compared to those without (239.0 ± 125.1 vs. 83.6 ± 51.3 pmol/mg/min, <italic>p</italic> = 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<sub>2</sub>O<sub>2</sub> production, further implicating a potential role of NOX4 in atrial remodeling. <bold>Conclusion:</bold> Our data represent the first implication that NOX4-derived H<sub>2</sub>O<sub>2</sub> may play an important role in the etiologies of AF.</p>