Oxidized LDL contains inflammatory PAF-like phospholipids

Atherosclerosis has an underlying inflammatory component. Oxidation of low- density lipoprotein (LDL) particles to modified forms promotes atherogenesi s by supplying cholesterol and through the oxidative generation of agents t hat activate macrophages, smooth muscle and endothelial cells. A primary ta rget of oxidizing compounds, derived from cigarette smoke, dietary sources, exuberant inflammatory cell responses and normal cellular metabolism among other sources, are the esterified polyunsaturated fatty acids in the phosp holipid shell that surrounds the insoluble lipids of the lipoprotein core. One type of phospholipid oxidation product mimics the structure of the pote nt inflammatory mediator platelet-activating factor (PAF), and these oxidat ion products activate the PAF receptor found on platelets, monocytes and le ukocytes. Production of such PAF mimetics is, in contrast to the physiologi c generation of PAF, uncontrolled. PAF mimetics and other phospholipid oxid ation products are found in atherosclerotic lesions or even in blood after exposure to cigarette smoke. Here we summarized our data describing the str ucture, activity and metabolism of the PAF-like lipids found in atherogenic LDL particles. (C) 2001, Elsevier Science Inc.