Dosage response of atherosclerotic lesions to dietary cholesterol in rabbits

Thirty New Zealand White rabbits were fed diets containing 0 (control), 1, 2, 4, or 8 g cholesterol/kg diet for 12 weeks to determine the cholesterol dosageresponse of plasma cholesterol and triglycerides, and the development of atherosclerosis. The concentration of plasma cholesterol increased proportionally with the dietary cholesterol dosage during the first 4 weeks, then remained constant until the 12th week. The plasma triglycerides and TBARS concentrations gradually increased with feeding time when rabbits were fed 2 g dosages. Aortas from rabbits fed a 2 g dosage developed moderate to severe multifocal or diffusive atherosclerotic lesions. Aortas from rabbits fed 4 and 8 g dosages were diffusely affected with massive atherosclerotic lesions, and had severe calcification and Alcian blue-positive foci throughout the media of the aorta. These results indicate that at least 2 g of cholesterol/kg in the diet is needed to generate atherosclerotic lesions in rabbit aortas.