Characterization of cholesterol oxidation products formed by oxidative modification of low density lipoprotein

Oxidative modification of LDL is evidenced by alterations in both the protein and lipid components of the particle. Progressive oxidation of the apoprotein is associated with loss of specific amino acids and a gradual increase in electronegativity. Electronegative LDL has been isolated from human plasma (LDL-) by several groups using liquid chromatographic techniques and appears to be oxidized based on increased lipid peroxide levels and cholesterol oxidation products (ChOx). Formation of LDL- also takes place following Cu(2+)-induced oxidation. Cu(2+)-induced oxidation caused a small fraction of the normal unoxidized LDL (n-LDL) to convert to LDL-during the oxidative lag phase while minimal increases in conjugated dienes were apparent. After the lag phase, there was a further increase in LDL-, a rapid accumulation of conjugated dienes, and another more electronegative particle was formed (LDL2-). By the end of the lag phase, approximately 30% and 12% of the total LDL converted to LDL- and LDL2-, respectively. Nearly 40% of the total ChOx formed was present by the end of the lag period, accompanied by small increases in conjugated dienes. The major products accumulating during this time were 7-ketocholesterol, cholesterol-beta-epoxide and 7-alpha-hydroxycholesterol. Accumulation of predominated during the subsequent propagation phase. At the end of propagation phase there was a six fold increase in conjugated dienes and total ChOx increased eight-fold. It appears that a subpopulation of LDL rapidly converts to LDL-, representing a mildly oxidized but oxidant sensitive LDL population. Oxidation of cholesterol accompanies these early events in LDL oxidation with formation of specific ChOx.