Intake of flavanol-rich food or beverages was previously shown to ameliorate endothelial function and to enhance bioactivity of nitric oxide with individuals at risk for cardiovascular disease. Here, we examined whether the major dietary flavanol, (-)-epicatechin. counteracts the action of oxidized LDL on endothelial cells; an action considered pivotal for endothelial dysfunction in the pathogenesis of atherosclercsis. Oxidation by myeloperoxidase plus nitrite rendered human LDL cytotoxic towards endothelial cells. more so than oxidation by Cu2+. Oxidized LDL also caused a marked loss of endothelial NO synthase protein which did not occur in the presence of a proteasome inhibitor, lactacystin. Both actions of oxidized LDL, which were not evoked by native LDL. were effectively counteracted by (-)-epicatechin. We conclude that dietary flavanols contribute to protection of the integrity of endothelial cells not only by scavenging free radicals but also by maintaining endothelial NO synthase. (c) 2005 Elsevier Inc. All rights reserved.