TIME-COURSE OF OXYSTEROL FORMATION DURING IN-VITRO OXIDATION OF LOW-DENSITY-LIPOPROTEIN

Cholesterol oxidation products (oxysterols) have been implicated in se veral aspects of atherogenesis; they affect key enzymes in cholesterol homeostasis, induce calcification in vascular cells and possess cytot oxic properties. Oxysterols are formed during oxidative modification o f low density lipoprotein (LDL). Using a recently developed method bas ed on isotope dilution-mass spectrometry, the kinetics of formation of oxysterols during oxidation of LDL by cupric ions or soybean lipoxyge nase was studied. The same products, mainly 7- and 5-oxygenated choles terol, were formed by the two oxidation methods. Virtually no side-cha in oxidized oxysterols were formed. During the oxidations, preferentia lly esterified cholesterol was consumed and consumption of polyunsatur ated fatty acids and formation of conjugated dienes preceded the appea rance of oxysterols. Cholesterol 7-hydroperoxides potential cytotoxins , were present in LDL oxidized by copper or lipoxygenase.