Atherosclerosis in rabbits fed a low cholesterol diet for five years

Rabbits were fed a low cholesterol atherogenic diet for up to 5 years. Arterial lesions during the first 12 months consisted of smooth muscle cell and lipid accumulation in the intima, with smaller amounts of elastin and collagen. By 24 months, considerable degeneration and necrosis of smooth muscle foam cells had occurred, lipid had decreased in relative proportion, and collagen was predominant. These trends continued during the final 3 years. By 48 months most plaques were calcified and a few had hemorrhage. Atherosclerosis was extensive in rabbits with serum cholesterol concentrations greater than 300 mg/100 ml and minimal in rabbits with concentrations consistently less than 150 mg/100 ml. Thicker lesions tended to have more atheromas while thinner ones were more fibrous and less fatty. Significant regression of fatty streaks occurred in a group of rabbits fed the atherogenic diet for 2 years and a stock diet during the third year but more advanced lesions did not regress. This study illustrates the importance of time as a variable in atherogenesis, and demonstrates that modest hypercholesterolemia can lead to atherosclerosis in rabbits that is qualitatively unlike atherosclerosis induced in rabbits by cholesterol rich diets and that resembles several stages of human atherosclerosis.