Increased Plasma Oxidized Phospholipid:Apolipoprotein B-100 Ratio With Concomitant Depletion of Oxidized Phospholipids From Atherosclerotic Lesions After Dietary Lipid-Lowering

Abstract

Background— Oxidized phospholipids (OxPL) are pro-inflammatory. We evaluated whether changes in plasma levels of OxPL associated with apolipoprotein B-100 (apoB-100) reflect changes in OxPL content in atherosclerotic plaques during dietary-induced atherosclerosis progression and regression. Methods and Results— OxPL content was measured in plasma and immunohistochemically in aortic plaques with antibody E06 in cynomolgus monkeys and New Zealand White rabbits at baseline, after a high-fat/high-cholesterol diet and after reversion to normal chow. The OxPL/apoB ratio, representing the content of OxPL on individual apoB-100 particles, and Total apoB-OxPL (OxPL/apoB multiplied by plasma apoB levels), reflecting the OxPL content on all apoB-100 particles, were measured. Total apoB-OxPL plasma levels increased 3-fold ( P <0.0001) during hypercholesterolemia and decreased ≈75% ( P <0.0001) during reversion to normocholesterolemia. In contrast, OxPL/apoB levels decreased significantly ( P <0.0001) during hypercholesterolemia and increased significantly ( P =0.0002) during reversion to normocholesterolemia. Immunostaining revealed that during atherosclerosis progression OxPL co-localized with apoB-100, whereas during regression OxPL virtually disappeared. Conclusion— In the setting of overall reduction of plasma OxPL levels after dietary lipid-lowering, increases in the OxPL/apoB ratio reflect reduced content of OxPL in atherosclerotic plaques. These data suggest that changes in the OxPL/apoB ratio may reflect early atherosclerosis regression.