Isolevuglandins, oxidatively truncated phospholipids, and atherosclerosis.
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.
Salomon
Robert G
RG
Department of Chemistry, Case Western Reserve University, Cleveland, OH 44106-7078, USA. rgs@case.edu
D001161:Arteriosclerosis / Q000453:epidemiology*; D006801:Humans; D007982:Levulinic Acids; D010084:Oxidation-Reduction; D010743:Phospholipids / Q000737:chemistry*; D011458:Prostaglandins E / Q000737:chemistry*; D011506:Proteins / Q000737:chemistry; D012307:Risk Factors
D007982:Levulinic Acids; D010743:Phospholipids; D011458:Prostaglandins E; D011506:Proteins; C032246:levulinic acid