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

Isolated human low density lipoprotein (LDL) was oxidized with either cupric ions or soybean lipoxygenase and linoleic acid. Cholesterol oxi dation products (oxysterols) were determined by isotope dilution gas c hromatography-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 simila r concentrations as the well-known cytotoxic cholestane-3 beta,5 alpha ,6 beta-triol during both copper- and lipoxygenase-mediated LDL oxidat ion. Furthermore, two epimeric cholest-5-ene-3 beta,4-diols were ident ified 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-atheroscler otic vessels. In vitro oxidation of LDL under an O-18(2) atmosphere re vealed that molecular oxygen was the only source of the oxygen functio ns at C-4 in the cholest-5-ene-3 beta,4-diols. Taken together, these f indings suggest that the cholest-5-ene-3 beta,4-diols in atherosclerot ic plaques are formed by autoxidation.