Role of gp91phox-containing NADPH oxidase in left ventricular remodeling induced by intermittent hypoxic stress
Role of gp91phox-containing NADPH oxidase in left ventricular remodeling induced by intermittent hypoxic stress
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DOI：
10.1152/ajpheart.91496.2007
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发表时间：
2008-05-01
影响因子：
4.8
通讯作者：
Kitaura, Yasushi
中科院分区：
文献类型：
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作者：
Hayashi, Tetsuya;Yamashita, Chika;Kitaura, Yasushi
睡眠呼吸暂停综合征引起的间歇性缺氧与心血管疾病有关。然而，间歇性缺氧应激加速心血管疾病的确切机制在很大程度上尚不清楚。本研究旨在探讨含gp91（phox）的NADPH氧化酶在小鼠间歇性缺氧应激诱导的左心室（LV）重构中的作用。雄性gp91（phox）缺乏（gp91(-/-)）小鼠（n = 26）和野生型（n = 39）小鼠（n = 39）在7-12周龄时暴露于间歇性缺氧（30 s的4.5-5.5% O-2，然后30 s的21% O-2，白天8小时/天）或正常缺氧10天。野生型或gp91（-/-）小鼠的平均血压和左室收缩压和舒张功能均未因间歇性缺氧而改变，但右心室收缩压有升高的趋势。在野生型小鼠中，间歇性缺氧应激显著增加左室心肌细胞直径和间质纤维化。此外，间歇性缺氧应激增加了野生型小鼠的超氧化物生成、4-羟基-2-壬烯醛蛋白、tnf - α和转化生长因子- β mRNA以及NF-kappa B结合活性，但对gp91（-/-）小鼠没有影响。这些结果表明，含gp91（phox）的NADPH氧化酶通过增加氧化应激在间歇性缺氧诱导的左室重塑的病理生理中起着至关重要的作用。
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% O-2 followed by 30 s of 21% O-2 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-alpha and transforming growth factor-beta mRNA, and NF-kappa 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.