NOX4-dependent hydrogen peroxide overproduction in human atrial fibrillation and HL-1 atrial cells

Relationship to hypertension

Jun Zhang, Ji Youn Youn, Antony Y. Kim, Rafael J. Ramirez, Ling Gao, Doan Ngo, Peng-Sheng Chen, Jennifer Scovotti, Aman Mahajan, Hua Cai

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Background/Objectives: 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. Methods and Results: Patients with AF were older than those without (58.8± 11.7 vs. 47.8±19.2, p = 0.047). Whereas total OZ.ast;~ production (determined by electron spin resonance) was similar in patients with and without AF, H2O2 production was more than doubled in AF patients (149.8 ±26.28 vs. 66.9±7.14pmol/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 H2O2 production compared to those without (239.0± 125.1 vs. 83.6± 51.3pmol/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 H2O2 production, further implicating a potential role of NOX4 in atrial remodeling. Conclusion: Our data represent the first implication that NOX4-derived H 2O 2 may play an important role in the etiologies of AF.

Original languageEnglish (US)
Article numberArticle 140
JournalFrontiers in Physiology
Volume3 JUN
DOIs
StatePublished - 2012
Externally publishedYes

Fingerprint

Atrial Fibrillation
Hydrogen Peroxide
Protein Isoforms
Hypertension
Atrial Remodeling
NADPH Oxidase
Electron Spin Resonance Spectroscopy
Angiotensin II
Cardiac Arrhythmias
Reactive Oxygen Species
Oxidative Stress
Up-Regulation
Stroke

Keywords

  • Angiotensin II
  • Atrial fibrillation
  • HL-1 cells
  • Hydrogen peroxide
  • Hypertension
  • NADPH oxidase
  • Nox4

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

NOX4-dependent hydrogen peroxide overproduction in human atrial fibrillation and HL-1 atrial cells : Relationship to hypertension. / Zhang, Jun; Youn, Ji Youn; Kim, Antony Y.; Ramirez, Rafael J.; Gao, Ling; Ngo, Doan; Chen, Peng-Sheng; Scovotti, Jennifer; Mahajan, Aman; Cai, Hua.

In: Frontiers in Physiology, Vol. 3 JUN, Article 140, 2012.

Research output: Contribution to journalArticle

Zhang, Jun ; Youn, Ji Youn ; Kim, Antony Y. ; Ramirez, Rafael J. ; Gao, Ling ; Ngo, Doan ; Chen, Peng-Sheng ; Scovotti, Jennifer ; Mahajan, Aman ; Cai, Hua. / NOX4-dependent hydrogen peroxide overproduction in human atrial fibrillation and HL-1 atrial cells : Relationship to hypertension. In: Frontiers in Physiology. 2012 ; Vol. 3 JUN.
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abstract = "Background/Objectives: 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. Methods and Results: Patients with AF were older than those without (58.8± 11.7 vs. 47.8±19.2, p = 0.047). Whereas total OZ.ast;~ production (determined by electron spin resonance) was similar in patients with and without AF, H2O2 production was more than doubled in AF patients (149.8 ±26.28 vs. 66.9±7.14pmol/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 H2O2 production compared to those without (239.0± 125.1 vs. 83.6± 51.3pmol/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 H2O2 production, further implicating a potential role of NOX4 in atrial remodeling. Conclusion: Our data represent the first implication that NOX4-derived H 2O 2 may play an important role in the etiologies of AF.",
keywords = "Angiotensin II, Atrial fibrillation, HL-1 cells, Hydrogen peroxide, Hypertension, NADPH oxidase, Nox4",
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AU - Youn, Ji Youn

AU - Kim, Antony Y.

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AU - Gao, Ling

AU - Ngo, Doan

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AU - Scovotti, Jennifer

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N2 - Background/Objectives: 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. Methods and Results: Patients with AF were older than those without (58.8± 11.7 vs. 47.8±19.2, p = 0.047). Whereas total OZ.ast;~ production (determined by electron spin resonance) was similar in patients with and without AF, H2O2 production was more than doubled in AF patients (149.8 ±26.28 vs. 66.9±7.14pmol/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 H2O2 production compared to those without (239.0± 125.1 vs. 83.6± 51.3pmol/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 H2O2 production, further implicating a potential role of NOX4 in atrial remodeling. Conclusion: Our data represent the first implication that NOX4-derived H 2O 2 may play an important role in the etiologies of AF.

AB - Background/Objectives: 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. Methods and Results: Patients with AF were older than those without (58.8± 11.7 vs. 47.8±19.2, p = 0.047). Whereas total OZ.ast;~ production (determined by electron spin resonance) was similar in patients with and without AF, H2O2 production was more than doubled in AF patients (149.8 ±26.28 vs. 66.9±7.14pmol/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 H2O2 production compared to those without (239.0± 125.1 vs. 83.6± 51.3pmol/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 H2O2 production, further implicating a potential role of NOX4 in atrial remodeling. Conclusion: Our data represent the first implication that NOX4-derived H 2O 2 may play an important role in the etiologies of AF.

KW - Angiotensin II

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