Chronic intermittent hypoxia activates nuclear factor-κB in cardiovascular tissues in vivo
Section snippets
Materials and methods
Animal CIH exposure protocol. The institutional animal care and use committee approved this study protocol. To mimic the cyclic episodes of hypoxia and its subsequent re-oxygenation seen in OSA patients, we developed a mouse model of CIH. We placed sham and CIH exposed mice in separate, but identical plexiglass exposure chambers that we have previously described in detail [28]. The fractional oxygen concentration (FcO2) in the CIH exposure chamber was reduced to a nadir of 6.5–7%, stabilized at
CIH exposure activates NF-κB cardiovascular tissues
To examine the potential role of the NF-κB pathway in CIH-induced cardiovascular dysfunction and inflammation, we first examined whether CIH causes NF-κB activation. We exposed mice to sham and CIH for 1, 2, 4, 8, and 14 days, and assayed NF-κB binding activity in heart and aorta of these mice. We also studied lung tissue, because lungs are enriched in microvasculature. The specificity of the NF-κB DNA/protein binding was confirmed in competition experiments (data not shown). We found that CIH
Discussion
The novel finding of this study is that CIH is an important pathological factor that activates NF-κB pathway in vivo. Exposure of mice to CIH activates NF-κB in an exposure time-dependent manner. Vascular tissue appears to be more sensitive to CIH, compared with other tissues. Activation of NF-κB by CIH is accompanied by increased cardiovascular expression of iNOS protein, which is a well-known NF-κB-dependent gene product. In addition, patients with OSA, who are exposed to CIH nightly as a
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