Oxidative stress and the vascular wall: NADPH oxidases take center stage.

The contemporary notion that oxidative stress contributes to vascular wall pathology dates back some 25 years, when chemical modification of LDL was found to permit macrophage foam cell formation,1 and subsequent data indicated that vascular cells promoted LDL lipid oxidation (eg, LDL oxidation) to produce a similarly modified LDL.2 It is now clear, however, that oxidative stress in the vascular wall involves much more than the oxidation of LDL lipids. Risk factors for atherosclerosis are associated with an increased arterial wall flux of reactive oxygen species that not only may oxidize biological targets (ie, lipids), but also directly produce phenotypic changes in vascular cells such as inducing smooth muscle cell proliferation, adhesion molecule expression, and premature senescence.3 Many of these cellular responses have been implicated in both the development and the clinical manifestations of atherosclerosis.