title: Role of gp91phox-containing NADPH oxidase in left ventricular remodeling induced by intermittent hypoxic stress.
abstract: 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-kappaB 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.
authors.affiliation: Department of Internal Medicine III, Osaka Medical College, 2-7 Daigakumachi, Takatsuki, Osaka, Japan. in3015@poh.osaka-med.ac.jp
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Hayashi
authors.forename: Chika
authors.initials: C
authors.lastname: Yamashita
authors.forename: Chika
authors.initials: C
authors.lastname: Matsumoto
authors.forename: Chol-Jun
authors.initials: CJ
authors.lastname: Kwak
authors.forename: Kiwako
authors.initials: K
authors.lastname: Fujii
authors.forename: Tomoko
authors.initials: T
authors.lastname: Hirata
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Miyamura
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Mori
authors.forename: Akira
authors.initials: A
authors.lastname: Ukimura
authors.forename: Yoshikatsu
authors.initials: Y
authors.lastname: Okada
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Matsumura
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kitaura
mesh_terms: D000447:Aldehydes / Q000097:blood; D000818:Animals; D001794:Blood Pressure; D004195:Disease Models, Animal; D000860:Hypoxia / Q000150:complications* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008054:Lipid Peroxides / Q000097:blood; D008297:Male; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013481:Superoxides / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D018487:Ventricular Dysfunction, Left / Q000209:etiology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D017725:Ventricular Pressure; D020257:Ventricular Remodeling
chemical_list: D000447:Aldehydes; D015850:Interleukin-6; D008054:Lipid Peroxides; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; C488842:Cybb protein, mouse; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; C027576:4-hydroxy-2-nonenal