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