Lipid Oxidation and Cardiovascular Disease: Introduction to a Review Series

Abstract

A therosclerosis and the associated adverse complications of cardiovascular disease are major causes of morbidity and mortality in people living a Western lifestyle. A role for excess cholesterol in the pathophysiology of atherosclerosis is clear. However, additional mechanisms driving the relevant pathological changes in a chronic disease such as atherosclerosis are those that constitute the acute inflammatory response.1 The essential elements of a physiological, and regulated, inflammatory response starts with stimulated endothelium,2 displaying adhesive molecules for circulating white blood cells. This is accompanied by localized production of cell type–specific agonists for adherent monocytes, neutrophils, or lymphocytes by the activated endothelium.3 These agonists then activate the migratory instruction set of adherent or rolling cells positioned to receive both adhesion- and agonist-related stimuli from activated vascular endothelial cells.4 Lipid oxidation products formed by virtually every vascular cell type participate in orchestrating these processes. We also have recently come to appreciate that the inflammatory process is actively limited by activation of a resolution phase, often via generation of structurally specific oxidized lipids whose function is to orchestrate resolution of inflammation.5 The overall goal of this review series is to place recent observations and insights in rapidly developing areas of lipid oxidation into the framework of cardiovascular disease. Enzymatic and free radical oxidation have prominent roles in cardiovascular disease through their oxidative modification of existing molecules. Lipids are primary targets of this modification because they are the primary repository of oxidizable olefinic or double bonds. Oxidized lipids are best understood as oxygenated arachidonic acid products, the prostaglandins, leukotrienes, and thromboxane A2, that have diverse and potent effects throughout the inflammatory and reparative responses. These oxidized lipid mediators are …