cytellin and Aortic-Diseases

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.. 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.. 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.. 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.

Topics: Animals; Aorta; Aortic Diseases; Apolipoproteins E; Atherosclerosis; Cell Movement; Cells, Cultured; Cholesterol; Cyclodextrins; Disease Models, Animal; Endothelial Progenitor Cells; Hydroxycholesterols; Male; Mice, Inbred C57BL; Mice, Knockout; Oxidative Stress; Reactive Oxygen Species; Sitosterols; Time Factors; Vasodilation

Cholesterol analogs have been used to treat hypercholesterolemia. The present study was to examine the effect of dihydrocholesterol (DC) on plasma total cholesterol (TC) compared with that of β-sitosterol (SI) in hamsters fed a high cholesterol diet.. Forty-five male hamsters were randomly divided into 6 groups, fed either a non-cholesterol diet (NCD) or one of five high-cholesterol diets without addition of DC and SI (HCD) or with addition of 0.2% DC (DA), 0.3% DC (DB), 0.2% SI (SA), and 0.3% SI (SB), respectively, for 6 weeks. Results showed that DC added into diet at a dose of 0.2% could reduce plasma TC by 21%, comparable to that of SI (19%). At a higher dose of 0.3%, DC reduced plasma TC by 15%, less effective than SI (32%). Both DC and SI could increase the excretion of fecal sterols, however, DC was more effective in increasing the excretion of neutral sterols but it was less effective in increasing the excretion of acidic sterols compared with SI. Results on the incorporation of sterols in micellar solutions clearly demonstrated both DC and SI could displace the cholesterol from micelles with the former being more effective than the latter.. DC was equally effective in reducing plasma cholesterol as SI at a low dose. Plasma TC-lowering activity of DC was mediated by inhibiting the cholesterol absorption and increasing the fecal sterol excretion.

Topics: Adipose Tissue; Animal Feed; Animals; Anticholesteremic Agents; Aortic Diseases; Atherosclerosis; Bile Acids and Salts; Cholestanol; Cholesterol; Cholesterol, Dietary; Cricetinae; Drug Evaluation, Preclinical; Feces; Gene Expression Profiling; Hyperlipoproteinemia Type II; Intestinal Absorption; Lipids; Lipoproteins; Liver; Male; Mesocricetus; Metabolic Networks and Pathways; Micelles; Molecular Structure; Organ Size; Plaque, Atherosclerotic; Random Allocation; RNA, Messenger; Sitosterols; Sterols; Viscera