Abstract
Intermittent hypoxia seems to be a major pathomechanism of obstructive sleep apnea-associated progression of atherosclerosis. The goal of the present study was to assess the influence of hypoxia on endothelial function depending on the initial stage of vasculopathy. We used 16 ApoE−/− mice were exposed to a 6-week-intermittent hypoxia either immediately (early preatherosclerosis) or after 5 weeks of high-cholesterol diet (advanced preatherosclerosis). Another 16 ApoE−/− mice under normoxia served as corresponding controls. Endothelial function was measured by an organ bath technique. Blood plasma CD31+/annexin V+ endothelial microparticles as well as sca1/flk1+ endothelial progenitor cells in blood and bone marrow were analyzed by flow cytometry. The findings were that intermittent hypoxia impaired endothelial function (56.6 ± 6.2 % of maximal phenylephrine-induced vasoconstriction vs. 35.2 ± 4.1 % in control) and integrity (increased percentage of endothelial microparticles: 0.28 ± 0.05 % vs. 0.15 ± 0.02 % in control) in early preatherosclerosis. Peripheral repair capacity expressed as the number of endothelial progenitor cells in blood was attenuated under hypoxia (2.0 ± 0.5 % vs. 5.3 ± 1.9 % in control), despite the elevated number of these cells in the bone marrow (2.0 ± 0.4 % vs. 1.1 ± 0.2 % in control). In contrast, endothelial function, as well as microparticle and endothelial progenitor cell levels were similar under hypoxia vs. control in advanced preatherosclerosis. We conclude that hypoxia aggravates endothelial dysfunction and destruction in early preatherosclerosis.
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Acknowledgements
This work was supported by Gerok Grant of the Medical Faculty, University of Bonn. We would like to thank Catharina Lahrmann, Michaela Matthey Kathrin Paul, Sabine Ring, Theresa Schmitz, and Heike Slomka for the invaluable technical support.
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The authors declare no conflicts of interest in relation to this article.
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Tuleta, I. et al. (2015). Intermittent Hypoxia Impairs Endothelial Function in Early Preatherosclerosis. In: Pokorski, M. (eds) Pulmonary Function. Advances in Experimental Medicine and Biology(), vol 858. Springer, Cham. https://doi.org/10.1007/5584_2015_114
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DOI: https://doi.org/10.1007/5584_2015_114
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