LDL(-) IS A LIPID HYDROPEROXIDE-ENRICHED CIRCULATING LIPOPROTEIN

A subclass of LDL described on the basis of its greater electronegativ ity and oxidative status is further characterized using a new, highly sensitive single photon counting technique to measure lipid hydroperox ides. We describe in this report that these particles, which we refer to as LDL(-), are enriched in lipid peroxides and other peroxidation p roducts as compared to the bulk of the unmodified, normal LDL (nLDL) r ecovered from human plasma. This chemiluminescence-based, single photo n counting technique has unique advantages in that analyses are perfor med on whole LDL, thus avoiding artifactual lipid peroxidation during lipid extraction. Evidence for increased amounts of lipid hydroperoxid es in LDL(-) versus nLDL are in agreement cvith other analytical metho ds such as measurement of conjugated dienes as well as cholesterol oxi dation 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 modi fication of the latter. Thus, LDL(-) has significantly lower proportio ns of the oxidizable amino acids histidine and lysine, and marked diff erences in other neutral and acidic amino acids. The deficit in specif ic amino acids is in agreement with a reduced TNBS reactivity and incr eased relative electrophoretic mobility of LDL(-). We postulate that L DL(-) is a major carrier of lipid hydroperoxides associated with plasm a LDL and may arise from oxidative events in the vasculature and/or by ingestion of peroxide-enriched meals.