Cellular pathology of progressive atherosclerosis in the WHHL rabbit. An animal model of familial hypercholesterolemia

This report describes the features of developing atherosclerosis in the Watanabe heritable hyperlipidemic (WHHL) rabbit, an animal model of human familial hypercho-lesterolemia. Observations were made in 18 homozygous WHHL rabbits, aged 4 days to 15 months, fed standard rabbit chow; seven control New Zealand white rabbits fed a similar diet, and four New Zealand white rabbits fed rabbit chow containing 2 % choles-terol and 10 % corn oil for 2 weeks. The WHHL rabbits showed evidence of progressive disease of the aorta with accumulation of strongly birefringent llpid in intimal lesions, Including fatty streaks, raised foam cell lesions, and plaques (atheromas), as well as in the media. As seen by electron microscopy, the cellular population of the intimal lesions consisted predominantly of smooth muscle cells with lipid deposits and lipid-laden foam cells. Llpid deposits occurred as cytoplasmic neutral lipid droplets and as multilamellar bodies. In addition to advanced atherosclerosis of the aorta, a 15-month-old WHHL rabbit also had focal coronary atherosclerosis and subcutaneous xantho-mas. The New Zealand white rabbits fed a high cholesterol and fat diet for 2 weeks showed early intimal lipid accumulation in the aorta and prominent lipid accumulatio