Similarity in the distribution of F₂-isoprostanes in the lipid subfractions of atherosclerotic plaque and in vitro oxidised low density lipoprotein

Abstract

Oxidation of low density lipoprotein (LDL) in vivo is thought to play a critical role in the initiation of atherosclerosis. F₂-isoprostanes are compounds resulting from non-enzymatic oxidation of arachidonic acid and elevated levels are present in human atherosclerotic plaque. However, little is known about the formation of F₂-isoprostanes in plaque lesions or their distribution in lipid subclasses. Given that LDL and tissue lipid subfractions (such as phospholipids, cholesterol esters and triglycerides) all contain significant levels of arachidonic acid, the aim of this study was to examine the relative distribution of F₂-isoprostanes in the different lipid fractions of LDL oxidised in vitro, and compare this to the distribution in atherosclerotic plaque. The results reveal that while the majority of F₂-isoprostanes are present in the phospholipid or surface lipid fractions, the core lipids (cholesterol esters/triglycerides) contribute at least 10% of the total F₂-isoprostanes in both LDL oxidised in vitro and human atherosclerotic plaque. The remarkably similar profiles between the oxidised LDL and advanced atherosclerotic plaque suggests oxidation in vivo, is predominantly via non-enzymatic processes directed towards the surface lipids.