Oliver Weingärtner1, Constanze Husche2, Hans F Schött2, Timo Speer3, Michael Böhm4, Charlotte M Miller5, Florence McCarthy5, Jogchum Plat6, Dieter Lütjohann2, Ulrich Laufs4. 1. 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. 2. Institute for Clinical Chemistry and Clinical Pharmacology, University Clinics Bonn, Germany. 3. Klinik für Innere Medizin IV, Klinik für Nephrologie und Hypertensiologie, Universitätsklinikum des Saarlandes, Homburg/Saar, Germany. 4. Klinik für Innere Medizin III, Kardiologie, Angiologie und Internistische Intensivmedizin, Universitätsklinikum des Saarlandes, Homburg/Saar, Germany. 5. Department of Chemistry and ABCRF, University College Cork, Western Road, Cork, Ireland. 6. Department of Human Biology, Maastricht University, Maastricht, The Netherlands.
Abstract
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.
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.
Authors: Sabine Baumgartner; Rouyanne T Ras; Elke A Trautwein; Maurice C J M Konings; Ronald P Mensink; Jogchum Plat Journal: J Lipid Res Date: 2019-08-27 Impact factor: 5.922
Authors: Jerad H Dumolt; Sandhya K Radhakrishnan; Mohammed H Moghadasian; Khuong Le; Mulchand S Patel; Richard W Browne; Todd C Rideout Journal: J Nutr Biochem Date: 2017-09-28 Impact factor: 6.048
Authors: Shana R Watson; Kara M Cooper; Piaomu Liu; Nazli Gharraee; Liya Du; Savannah M Han; Edsel A Peña; Michael A Sutton; John F Eberth; Susan M Lessner Journal: Am J Physiol Heart Circ Physiol Date: 2021-01-01 Impact factor: 4.733
Authors: Tarek A M Almabrouk; Anna D White; Azizah B Ugusman; Dominik S Skiba; Omar J Katwan; Husam Alganga; Tomasz J Guzik; Rhian M Touyz; Ian P Salt; Simon Kennedy Journal: Front Physiol Date: 2018-02-09 Impact factor: 4.566