Comparative atherogenic effects of cholesterol and cholesterol oxides.

Previous findings indicating that the oxidation products of cholesterol are associated with atherogenicity have led to a comparative study of the subchronic effects of feeding rabbits purified cholesterol, oxidized cholesterols free of cholesterol and cholesterol esters, or a mixture of cholesterol and oxidized cholesterols. Macroscopically, the cholesterol-fed animals exhibited 6-fold more arterial lesions than the animals fed cholesterol-free oxidized cholesterols. Microscopically, there was no statistically significant difference from the control in the number of histochemically-defined lesions in any of the groups. However, the lesions in the cholesterol-fed group were more severe, as indicated by a statistically significant increase in the magnitude of the lesions. This increased severity was also characterized by greater frequency and intensity of Azure A/Thionin, VonKossa, and Horseradish Peroxidase-Wheat Germ Agglutinin staining. Electron-microscopic studies of normal appearing arterial tissues showed an increased density of viable smooth muscle cells and an increase in vacuolar extracellular debris in the cholesterol-fed group. Oxidized cholesterols in the concentrations and relative compositions administered here are markedly less atherogenic to rabbits than highly purified cholesterol.