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Publication : Vascular effects of oxysterols and oxyphytosterols in apoE -/- mice.

First Author  Weingärtner O Year  2015
Journal  Atherosclerosis Volume  240
Issue  1 Pages  73-9
PubMed ID  25765595 Mgi Jnum  J:330948
Mgi Id  MGI:6868813 Doi  10.1016/j.atherosclerosis.2015.02.032
Citation  Weingartner O, et al. (2015) Vascular effects of oxysterols and oxyphytosterols in apoE -/- mice. Atherosclerosis 240(1):73-9
abstractText  OBJECTIVES: The aim of our study was to investigate vascular effects of oxysterols and oxyphytosterols on reactive oxygen species (ROS), endothelial progenitor cells, endothelial function and atherogenesis. METHODS: Male apoE-/-mice were treated with cholesterol, sitosterol, 7-ss-OH-cholesterol, 7-ss-OH-sitosterol, or cyclodextrin by daily intraperitoneal application. The respective concentrations in the plasma and in the arterial wall were determined by gas chromatography-flame ionization or mass spectrometry. ROS production was assessed by electron-spin resonance spectroscopy in the aorta, endothelial function of aortic rings and atherosclerosis in the aortic sinus was quantitated after 4 weeks. RESULTS: Compared to vehicle, there was no difference in plasma cholesterol levels and arterial wall concentrations after i.p. application of cholesterol. 7-ss-OH-cholesterol concentrations were increased in the plasma (33.7+/-31.5 vs. 574.57.2+/-244.92 ng/ml) but not in the arterial wall (60.1+/-60.1 vs. 59.3+/-18.2 ng/mg). Sitosterol (3.39+/-0.96 vs. 8.16+/-4.11 mg/dL; 0.08+/-0.04 vs. 0.16+/-0.07 mug/mg, respectively) and 7-ss-OH-sitosterol concentrations (405.1+/-151.8 vs. 7497+/-3223 ng/ml; 0.24+/-0.13 vs. 16.82+/-11.58 ng/mg, respectively) increased in the plasma and in the aorta. The i.p-application of the non-oxidized cholesterol or sitosterol did not induce an increase of plasma oxysterols or oxyphytosterols concentrations. Oxidative stress in the aorta was increased in 7-ss-OH-sitosterol treated mice, but not in mice treated with cholesterol, sitosterol, or 7-ss-OH-cholesterol. Moreover, cholesterol, sitosterol, 7-ss-OH-cholesterol, and 7-ss-OH-sitosterol did not affect endothelial-dependent vasodilation, or early atherosclerosis. CONCLUSION: Increased oxyphytosterol concentrations in plasma and arterial wall were associated with increased ROS production in aortic tissue, but did not affect endothelial progenitor cells, endothelial function, or early atherosclerosis.
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