UBC Theses and Dissertations
Endothelial dysfunction in mice subjected to intermittent hypoxia and fed a high fat diet Badran, Mohammad Salah El Deen
Background: Obstructive sleep apnea (OSA) and obesity are major independent risk factors for cardiovascular disease; nearly 70% of OSA patients are obese. This thesis examines the vascular effects of sleep disordered breathing in a mouse model with diet-induced obesity. Markers of oxidative stress and inflammation were also determined in these mice. Methods: Mice were divided into four groups for 6 weeks: i) mice subjected to intermittent hypoxia alone (IH) ii) mice fed a high fat (60%) diet alone (HFIA), iii) mice subjected to intermittent hypoxia and a high fat diet and (HFIH) iv) mice subjected to intermittent air (IA) alone. Vasodilatory and contractility responses were examined in isolated aortas to assess changes in endothelial function. Markers of oxidative stress (MDA and TAC) and inflammation (CRP) levels were measured and finally, eNOS expression in the aortas was evaluated. Results: Only mice subjected to intermittent hypoxia and a high fat diet showed endothelial dysfunction. Intermittent hypoxia alone increased plasma oxidative stress and inflammatiory markers but adding high fat diet further increased those markers. High fat diet alone did not increase oxidative stress or inflammation. Total antioxidant capacity and aortic eNOS expression were not significantly different between the groups. Conclusion: there is a synergistic effect between intermittent hypoxia and high fat diet since only their combination of caused endothelial dysfunction. These data suggest that aortic endothelial dysfunction may be mediated by increased oxidative stress and inflammation.
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