Mature human atherosclerotic plaque contains peroxidized phosphatidylcholine as a major lipid peroxide

Abstract

The initial stage of atherosclerotic plaque formation involves oxidation of the phosphatidyl-choline moiety of low density lipoprotein (LDL) and subsequent uptake by macrophages. Ongoing uptake in developing plaque also may involve oxidized LDL and would require an oxidizing environment in plaque lipids. Atherosclerotic plaque lipids from 12 patients undergoing peripheral vascular procedures were extracted in chloroform: methanol (2:1). This extract was applied to a 25 cm 5 micron silica HPLC column and eluted with a ternary gradient mobile phase utilizing a laser light scattering (ELSD) mass detector. Individual lipid fractions were then analyzed. Cholesterol, both free and esterified, was the most prominent lipid in plaque (104 +/- 74 mg/gm tissue. However, lipid peroxides were present in much higher concentrations (3.52 +/- 2.84 FU X 10(4)/mg phospholipid) and overall level (21.27 +/- 10.10 FU X 10(4)/gm plaque) in the phospholipid component (*p< 0.05). Phosphatidyl-choline (PC) accounted for 63% of the total phospholipid peroxides recovered (6.31 +/- 5.09 mg/gm plaque; *p<0.05). PC and phosphatidylinositol (PI) content were linearly related to lipid peroxide fluorescence (PC; r=0.696; p=0.01) (PI; r=0.809; p=0.001). Lipid peroxides in human atherosclerotic plaque are present primarily in the phospholipid component and phosphatidyl-choline forms the bulk of these peroxides. PC may play an important role in ongoing plaque lipid accumulation.