Isolevuglandins, oxidatively truncated phospholipids, and atherosclerosis

Abstract

Isolevuglandins (isoLGs) and oxidatively truncated phospholipids are products of lipid peroxidation. Some of these, especially isoLGs and gamma-hydroxyalkenal analogues (e.g., the 5-hydroxy-8-oxo-6-octenoic acid and 9-hydroxy-12-oxo-10-dodecenoic acid esters of 2-lysophosphatidylcholine, HOOA-PC or HODA-PC, respectively) of 4-hydroxy-2(E)-nonenal (HNE), damage proteins by covalent adduction, thereby interfering with their normal functions. These lipid-derived protein modifications may serve as dosimeters of oxidative injury. Elevated plasma levels of isoLG-protein epitopes are associated with atherosclerosis but are independent of total cholesterol, a classical risk factor. Both protein adducts and oxidatively truncated phospholipids (oxPL) can also elicit receptor-mediated cellular responses that include endocytosis of oxidized low-density lipoprotein (LDL) and expression of chemokines, which may foster infiltration of monocyte macrophages into the subendothelial space, where they become foam cells through unregulated endocytosis of oxidatively damaged LDL.