LDL- is a lipid hydroperoxide-enriched circulating lipoprotein

Abstract

A subclass of LDL described on the basis of its greater electronegativity and oxidative status is further characterized using a new, highly sensitive single photon counting technique to measure lipid hydroperoxides. We describe in this report that these particles, which we refer to as LDL-, are enriched in lipid peroxides and other peroxidation products as compared to the bulk of the unmodified, normal LDL (nLDL) recovered from human plasma. This chemiluminescence-based, single photon counting technique has unique advantages in that analyses are performed on whole LDL, thus avoiding artifactual lipid peroxidation during lipid extraction. Evidence for increased amounts of lipid hydroperoxides in LDL- versus nLDL are in agreement with other analytical methods such as measurement of conjugated dienes as well as cholesterol oxidation products. LDL- also has lower proportions of polyunsaturated fatty acids than nLDL. Analysis of the amino acid composition of apoB-100 and fatty acid composition of total LDL lipids also revealed major differences between nLDL and LDL- consistent with an oxidative modification of the latter. Thus, LDL- has significantly lower proportions of the oxidizable amino acids histidine and lysine, and marked differences in other neutral and acidic amino acids. The deficit in specific amino acids is in agreement with a reduced TNBS reactivity and increased relative electrophoretic mobility of LDL-. We postulate that LDL- is a major carrier of lipid hydroperoxides associated with plasma LDL and may arise from oxidative events in the vasculature and/ or by ingestion of peroxide-enriched meals.