Selective distribution of oxysterols in atherosclerotic lesions and human plasma lipoproteins.
The presence of oxidized sterols (oxysterols) in human serum and lesions has been linked to the initiation and progression of atherosclerosis. Data concerning the origin, identity and quantity of oxysterols in biological samples are controversial and inconsistent. This inconsistency may arise from different analytical methods or handling conditions used by different investigators. In the present study, oxysterol levels and distribution were analyzed by an optimized GC-MS method, in human atherosclerotic coronary and carotid lesions, in atherosclerotic apolipoprotein E deficient mice (E degrees mice) and in native and in vitro oxidized human low and high density lipoproteins. Oxysterol levels were analyzed with a limit of detection of 0.06 - 0.24 ng, with 25-hydroxycholesterol (25-OH) being the least sensitive. In human coronary and carotid lesions, obtained from endatherectomic samples, 27-hydroxycholesterol (27-OH) was the major oxysterol, with about 85% as sterols esterified to fatty acids. While total cholesterol and oxysterols levels were similar in both kinds of human lesions, oxysterol distribution was significantly different. In coronary lesions the mean levels of 27-OH and 7beta-hydroxycholesterol (7beta-OH) were 38% and 20% of total oxysterols, whereas in carotid lesions their mean levels were 66% and 5%, respectively. Unlike in human aortic lesions, 27-OH was entirely absent in E degrees mice, whereas the level of 7alpha-hydroxycholesterol (7alpha-OH) was 28% of the total oxysterols, vs. 5% in human coronary lesions. As 27-OH is an enzymatic product of cholesterol oxidation, this finding may indicate that such an enzymatic process does not take place in E degrees mice.
Vaya
J
J
Laboratory of Natural Medicinal Compounds, Migal-Galilee Technological Center, Kiryat Shmona 10200, Israel.
Aviram
M
M
Mahmood
S
S
Hayek
T
T
Grenadir
E
E
Hoffman
A
A
Milo
S
S
D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D001161:Arteriosclerosis / Q000097:blood / Q000378:metabolism*; D003324:Coronary Artery Disease / Q000097:blood / Q000378:metabolism / Q000601:surgery; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D006801:Humans; D006888:Hydroxycholesterols / Q000032:analysis* / Q000378:metabolism*; D008074:Lipoproteins / Q000097:blood / Q000378:metabolism*; D008075:Lipoproteins, HDL / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D010084:Oxidation-Reduction
D001057:Apolipoproteins E; D006888:Hydroxycholesterols; D008074:Lipoproteins; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; C011724:cholest-5-en-3 beta,7 alpha-diol; C076996:27-hydroxycholesterol; C007997:25-hydroxycholesterol