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This Article Full Text Full Text (PDF) All Versions of this Article: 294/5/H2197    most recent ajpheart.91496.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Hayashi, T. Articles by Kitaura, Y. PubMed PubMed Citation Articles by Hayashi, T. Articles by Kitaura, Y.

Role of gp91^phox-containing NADPH oxidase in left ventricular remodeling induced by intermittent hypoxic stress

¹Department of Internal Medicine III, ²Department of Pathology, Osaka Medical College, and ³Laboratory of Pathological and Molecular Pharmacology, Osaka University of Pharmaceutical Sciences, Takatsuki, Osaka, Japan

Submitted 19 December 2007 ; accepted in final form 28 February 2008

Intermittent hypoxia due to sleep apnea syndrome is associated with cardiovascular diseases. However, the precise mechanisms by which intermittent hypoxic stress accelerates cardiovascular diseases are largely unclear. The aim of this study was to investigate the role of gp91^phox-containing NADPH oxidase in the development of left ventricular (LV) remodeling induced by intermittent hypoxic stress in mice. Male gp91^phox-deficient (gp91^–/–) mice (n = 26) and wild-type (n = 39) mice at 7–12 wk of age were exposed to intermittent hypoxia (30 s of 4.5–5.5% O₂ followed by 30 s of 21% O₂ for 8 h/day during daytime) or normoxia for 10 days. Mean blood pressure and LV systolic and diastolic function were not changed by intermittent hypoxia in wild-type or gp91^–/– mice, although right ventricular systolic pressure tended to be increased. In wild-type mice, intermittent hypoxic stress significantly increased the diameter of cardiomyocytes and interstitial fibrosis in LV myocardium. Furthermore, intermittent hypoxic stress increased superoxide production, 4-hydroxy-2-nonenal protein, TNF- and transforming growth factor-β mRNA, and NF-B binding activity in wild-type, but not gp91^–/–, mice. These results suggest that gp91^phox-containing NADPH oxidase plays a crucial role in the pathophysiology of intermittent hypoxia-induced LV remodeling through an increase of oxidative stress.

oxidative stress; superoxide; cardiac hypertrophy; sleep apnea