Abstract 350: Role of gp91phox-containing NADPH Oxidase in Hypoxia-induced Left Ventricular Remodeling
Background: Intermittent hypoxia due to sleep apnea is associated with cardiovascular diseases. The mechanisms by which intermittent hypoxia accelerates cardiovascular diseases are still unclear. The aim of this study was to examine the role of NADPH oxidase, especially gp91phox subunit, in the development of left ventricular (LV) remodeling in mice exposed to repetitive severe hypoxia.
Methods: Male gp91phox-deficient mice (n=18) and wild-type mice (n=21) at 7 to 12 weeks of age, were kept under intermittent hypoxia (every 30 seconds with inspired oxygen fraction 4.5–5.5% for 8 hours per day during daytime) or normoxia for 10 days. Fine structure, percent fibrosis (%fibrosis), superoxide production and immunohistochemical expression of 4-hydroxy-2-nonenal protein (4-HNE) were examined in LV myocardium. The nuclear factor-κB (NF-κB) binding activity was evaluated by electrophoretic mobility shift assay.
Results: Systolic blood pressure and LV diastolic function were not changed by intermittent hypoxia in both wild-type and gp91phox-deficient mice. In wild-type mice, intermittent hypoxia significantly increased hypertrophy of cardiomyocytes and %fibrosis (Figure⇓). Furthermore, intermittent hypoxia increased superoxide production, 4-HNE expressions and NF-κB binding activity in wild-type mice, but not in gp91phox-deficient mice.
Conclusions: Intermittent hypoxia induced LV remodeling in wild-type mice, but not in gp91phox-deficient mice. This study suggests a pivotal role of gp91 phox-containing NADPH oxidase in the pathophysiology of hypoxia-induced LV remodeling through an increase of oxidative stress.