Abstract 664: Increased Plasma Oxidized Phospholipid:Apolipoprotein B-100 Ratio with Concomitant Depletion of Oxidized Phospholipids from Atherosclerotic Lesions Following Dietary Lipid Lowering: A Potential Biomarker of Early Atherosclerosis Regression
Background- Oxidized phospholipids (OxPL) are pro-inflammatory and pro-atherogenic. This study evaluated whether changes in plasma OxPL levels reflect changes in atherosclerotic plaque content of OxPL during dietary-induced atherosclerosis progression and regression.
Methods Plasma and aortic plaque OxPL content was evaluated in Cynomolgous monkeys and New Zealand White rabbits at baseline, following a high fat/cholesterol diet and after reverting to normal chow. Plasma OxPL levels were measured with antibody E06 and reported as the OxPL/apolipoprotein B100 (OxPL/apoB) ratio, measuring the content of OxPL on individual apoB particles, and as Total apoB-OxPL (i.e. OxPL/apoB ratio multiplied by plasma apoB levels), reflecting the OxPL content on all apoB particles. Aortic plaque content of OxPL was detected immunochemically.
Results-Total apoB-OxPL plasma levels increased significantly by 3-fold (P<0.0001) during hypercholesterolemia and decreased significantly (~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. There was strong OxPL immunostaining with E06 during hypercholesterolemia and progression of atherosclerosis, but a significant decrease in OxPL immunostaining after reversion to normocholesterolemia.
Conclusion- Increases in the OxPL/apoB ratio, in the setting of overall reduction of plasma OxPL levels, reflects reduced OxPL content in atherosclerotic plaques following dietary lipid lowering. These data suggest that the OxPL/apoB ratio may be a robust plasma biomarker in assessing atherosclerosis progression and regression.