Dietary cholesterol supplementation protects against endothelial cell dysfunction mediated by native and lipolyzed lipoproteins derived from rabbits fed high-corn oil diets

Epidemiologic studies indicate that dietary plants are negatively and dietary cholesterol positively correlated with the incidence of cardiovascular disease. However, 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 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) for 10 weeks. The cholesterol concentration in the CO+C diet was less than 30 mg cholesterol/100 g diet, which was sufficient to cause a significant rise in plasma and LDL cholesterol, but that did not lead to any detectable fatty steak or lesion formation. Compared with the native CO group, lipid hydroperoxide levels were significantly lower in both native lipoproteins (VLDL/LDL) and lipolyzed remnants of this lipoprotein mixture derived from rabbits fed CO+C. This may be attributable in part to the observed decrease in unsaturated fatty acids as a result of dietary cholesterol supplementation. Relative to native lipoproteins, endothelial cells exposed to lipolyzed lipoprotein remnants experienced a significant increase in oxidative stress, as evidenced by increased DCF fluorescence. NF-κB, an oxidative stress sensitive transcription factor, was markedly induced in cells treated with both native and lipolyzed lipoproteins derived from the CO group, compared to the CO+C group. Independent of lipolysis, oxidative stress was markedly decreased in cells exposed to lipoproteins derived from animals fed CO+C. Furthermore, dietary cholesterol supplementation protected endothelial cells against lipolytic remnant-mediated barrier dysfunction. These data continue to support the hypothesis that lipolytic lipoprotein remnants are atherogenic and that small amounts of supplemental cholesterol may provide antioxidant protection.