Cholesterol (C) protects against high corn oil-mediated endothelial cell (EC) dysfunction

Recent research suggests that unsaturated fats may be atherogenic because of their contribution to cellular oxidative stress and that cholesterol may exhibit antioxidant properties. To test this hypothesis, rabbits were fed for 10 weeks diets containing 2 g corn oil/100 g diet, supplemented either with 16 g/100 g diet of corn oil (CO) or CO plus added cholesterol (CO+C). Compared with the native CO group, lipid hydroperoxide levels were significantly lower in both native lipoproteins (LP) and lipolyzed remnants of this LP mixture derived from rabbits fed CO+C. Relative to native LP, EC exposure to lipolyzed LP remnants resulted in a significant increase in oxidative stress, as evidenced by increased DCF fluorescence. Independent of lipolysis, this oxidative stress was markedly decreased in cells exposed to LP derived from animals fed CO+C. NF-κB was markedly induced in cells treated with both native and lipolyzed LP derived from the CO group, compared to the CO+C group. Furthermore, dietary C supplementation protected EC against lipolytic remnant-mediated barrier dysfunction. These data continue to support the hypothesis that lipolytic LP remnants are atherogenic and that small amounts of supplemental C may provide antioxidant protection, if oxidative modification of LP is a critical issue in atherosclerosis.