Chronic intermittent hypoxia induces atherosclerosis by NF-κB-dependent mechanisms

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1822

Article

Song, D.^1,2  Fang, G.^1,2  Mao, S. -Z.^1,2  Ye, X.^1,2  Liu, G.^1,2  Gong, Y.³  Liu, S. F.^1,2,3 

[1] Feinstein Inst Med Res, Ctr Heart & Lung Res, Manhasset, NY 11030 USA

[2] Feinstein Inst Med Res, Ctr Pulm Crit Care & Sleep Med, Manhasset, NY 11030 USA

[3] Wenzhou Med Coll, Inst Hypoxia Study, Wenzhou, Zhejiang, Peoples R China

关键词: Atherosclerosis;    Cardiovascular risk factor;    Intermittent hypoxia;    Nuclear factor kappa B;    Obstructive sleep apnea;   

DOI  :  10.1016/j.bbadis.2012.07.010

来源: Elsevier

【 摘 要 】

Chronic intermittent hypoxia (CIH) causes atherosclerosis in mice fed a high cholesterol diet (HCD). The mechanisms by which CIH promotes atherosclerosis are incompletely understood. This study defined the mechanistic role of NF-kappa B pathway in CIH + HCD induced atherosclerosis. Wild type (WT) and mice deficient in the p50 subunit of NF-kappa B (p50-KO) were fed normal chow diet (ND) or HCD, and exposed to sham or CIH. Atherosclerotic lesions on the en face aortic preparation and cross-sections of aortic root were examined. In WT mice, neither CIH nor HCD exposure alone caused, but CIH + HCD caused evident atherosclerotic lesions on both preparations after 20 weeks of exposure. WT mice on ND and exposed to CIH for 35.6 weeks did not develop atherosclerotic lesions. P50 gene deletion diminished CIH + HCD induced NF-kappa B activation and abolished CIH + HCD induced atherosclerosis. P50 gene deletion inhibited vascular wall inflammation, reduced hepatic TNF-alpha level, attenuated the elevation in serum cholesterol level and diminished macrophage foam cell formation induced by CIH + HCD exposure. These results demonstrate that inhibition of NF-kappa B activation abrogates the activation of three major atherogenic mechanisms associated with an abolition of CIH + HCD induced atherosclerosis. NF-kappa B may be a central common pathway through which CIH + HCD exposure activates multiple atherogenic mechanisms, leading to atherosclerosis. (C) 2012 Elsevier B.V. All rights reserved.

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