title: Vascular effects of oxysterols and oxyphytosterols in apoE -/- mice.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Abteilung für Kardiologie, Klinikum Oldenburg, European Medical School Oldenburg-Groningen, Carl von Ossietzky Universität Oldenburg, Oldenburg, Germany; Klinik für Innere Medizin III, Kardiologie, Angiologie und Internistische Intensivmedizin, Universitätsklinikum des Saarlandes, Homburg/Saar, Germany. Electronic address: oweingartner@aol.com.
authors.forename: Oliver
authors.initials: O
authors.lastname: Weingärtner
authors.affiliation: Institute for Clinical Chemistry and Clinical Pharmacology, University Clinics Bonn, Germany.
authors.forename: Constanze
authors.initials: C
authors.lastname: Husche
authors.affiliation: Institute for Clinical Chemistry and Clinical Pharmacology, University Clinics Bonn, Germany.
authors.forename: Hans F
authors.initials: HF
authors.lastname: Schött
authors.affiliation: Klinik für Innere Medizin IV, Klinik für Nephrologie und Hypertensiologie, Universitätsklinikum des Saarlandes, Homburg/Saar, Germany.
authors.forename: Timo
authors.initials: T
authors.lastname: Speer
authors.affiliation: Klinik für Innere Medizin III, Kardiologie, Angiologie und Internistische Intensivmedizin, Universitätsklinikum des Saarlandes, Homburg/Saar, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Böhm
authors.affiliation: Department of Chemistry and ABCRF, University College Cork, Western Road, Cork, Ireland.
authors.forename: Charlotte M
authors.initials: CM
authors.lastname: Miller
authors.affiliation: Department of Chemistry and ABCRF, University College Cork, Western Road, Cork, Ireland.
authors.forename: Florence
authors.initials: F
authors.lastname: McCarthy
authors.affiliation: Department of Human Biology, Maastricht University, Maastricht, The Netherlands.
authors.forename: Jogchum
authors.initials: J
authors.lastname: Plat
authors.affiliation: Institute for Clinical Chemistry and Clinical Pharmacology, University Clinics Bonn, Germany.
authors.forename: Dieter
authors.initials: D
authors.lastname: Lütjohann
authors.affiliation: Klinik für Innere Medizin III, Kardiologie, Angiologie und Internistische Intensivmedizin, Universitätsklinikum des Saarlandes, Homburg/Saar, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Laufs
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D001018:Aortic Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D002784:Cholesterol / Q000097:blood / Q000494:pharmacology*; D003505:Cyclodextrins / Q000494:pharmacology; D004195:Disease Models, Animal; D066026:Endothelial Progenitor Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006888:Hydroxycholesterols / Q000494:pharmacology; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D012855:Sitosterols / Q000097:blood / Q000494:pharmacology*; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects
chemical_list: D001057:Apolipoproteins E; D003505:Cyclodextrins; D006888:Hydroxycholesterols; D017382:Reactive Oxygen Species; D012855:Sitosterols; C011486:hydroxysitosterol; C011724:cholest-5-en-3 beta,7 alpha-diol; C025473:gamma-sitosterol; D002784:Cholesterol
keywords: Atherosclerosis; Endothelial function; Oxyphytosterols; Oxysterols; Phytosterols; Sterols