| First Author | Song D | Year | 2012 |
| Journal | Biochim Biophys Acta | Volume | 1822 |
| Issue | 11 | Pages | 1650-9 |
| PubMed ID | 22846605 | Mgi Jnum | J:188032 |
| Mgi Id | MGI:5439033 | Doi | 10.1016/j.bbadis.2012.07.010 |
| Citation | Song D, et al. (2012) Chronic intermittent hypoxia induces atherosclerosis by NF-kappaB-dependent mechanisms. Biochim Biophys Acta 1822(11):1650-9 |
| abstractText | 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-kappaB pathway in CIH+HCD induced atherosclerosis. Wild type (WT) and mice deficient in the p50 subunit of NF-kappaB (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 20weeks of exposure. WT mice on ND and exposed to CIH for 35.6weeks did not develop atherosclerotic lesions. P50 gene deletion diminished CIH+HCD induced NF-kappaB 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-kappaB activation abrogates the activation of three major atherogenic mechanisms associated with an abolition of CIH+HCD induced atherosclerosis. NF-kappaB may be a central common pathway through which CIH+HCD exposure activates multiple atherogenic mechanisms, leading to atherosclerosis. |
