title: The oxysterols cholest-5-ene-3 beta,4 alpha-diol, cholest-5-ene-3 beta,4 beta-diol and cholestane-3 beta,5 alpha,6 alpha-triol are formed during in vitro oxidation of low density lipoprotein, and are present in human atherosclerotic plaques.
abstract: Isolated human low density lipoprotein (LDL) was oxidized with either cupric ions or soybean lipoxygenase and linoleic acid. Cholesterol oxidation products (oxysterols) were determined by isotope dilution gas chromatography-mass spectrometry. A new cholestane-3,5,6-triol isomer, cholestane-3 beta,5 alpha,6 alpha-triol, which has not previously been recognized as a cholesterol autoxidation product, was found at similar concentrations as the well-known cytotoxic cholestane-3 beta,5 alpha,6 beta-triol during both copper- and lipoxygenase-mediated LDL oxidation. Furthermore, two epimeric cholest-5-ene-3 beta,4-diols were identified in the oxidized LDL at similar concentrations. These two isomers were also identified in human atherosclerotic tissue in a ratio of 1:1 at a concentration more than 10-times higher than in non-atherosclerotic vessels. In vitro oxidation of LDL under an 18O2 atmosphere revealed that molecular oxygen was the only source of the oxygen functions at C-4 in the cholest-5-ene-3 beta,4-diols. Taken together, these findings suggest that the cholest-5-ene-3 beta,4-diols in atherosclerotic plaques are formed by autoxidation.
authors.affiliation: Department of Medical Laboratory Sciences and Technology, Karolinska Institutet, Huddinge University Hospital, Sweden.
authors.forename: O
authors.initials: O
authors.lastname: Breuer
authors.forename: S
authors.initials: S
authors.lastname: Dzeletovic
authors.forename: E
authors.initials: E
authors.lastname: Lund
authors.forename: U
authors.initials: U
authors.lastname: Diczfalusy
mesh_terms: D001161:Arteriosclerosis / Q000378:metabolism*; D002777:Cholestanols / Q000378:metabolism*; D003300:Copper / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D006888:Hydroxycholesterols / Q000378:metabolism*; D015227:Lipid Peroxidation; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008084:Lipoxygenase / Q000378:metabolism; D013058:Mass Spectrometry; D010103:Oxygen Isotopes; D013025:Glycine max / Q000201:enzymology
chemical_list: D002777:Cholestanols; D006888:Hydroxycholesterols; D008077:Lipoproteins, LDL; D010103:Oxygen Isotopes; C000474:cholestane-3,5,6-triol; C099828:cholest-5-ene-3,4-diol; D003300:Copper; D008084:Lipoxygenase