The occurrence and severity of spontaneous atherosclerotic lesions varies considerably among vertebrate animals. Gross atherosclerosis rarely develops in seals despite plasma lipid levels that are among the highest reported for mammals. We report here the sudden death of a 15 month old harbor seal with severe hypercholesterolemia and atherosclerosis.

The harbor seal was born at Sea World in San Diego in October 1987 and was eating normally until the time of death. It died suddenly on January 3, 1988 from a spontaneous rupture in the left ventricle and exsanguination. Gross examination revealed tuberous xanthomas on the face, tongue, fore flippers and hind flippers. The xanthomas ranged in size from 1-6 mm and were concentrated around the eyes and nose. The arterial vasculature had severe atherosclerosis, and all of the arteries 2 mm or less in diameter were severely stenotic from the presence of yellow-white plaque. Light microscopy of the arteries showed advanced, proliferative atherosclerotic lesions composed of extensive foam cells and extracellular lipid. The lungs, liver and kidneys were congested.

Serum samples taken two weeks and ten weeks prior to death were very turbid due to the accumulation of large, light scattering lipoprotein particles. The plasma concentrations of total cholesterol (TC) and triglycerides ranged from 4643-5590 mg/dl and 781-955 mg/dl, respectively. These are some of the highest plasma cholesterol concentrations ever reported for a vertebrate animal. The plasma was ultracentrifuged to separate the lipoprotein classes (chylomicrons, VLDL, LDL, HDL, density < 1.006 g/ml, 1.006-1.063 q/ml and 1.063-1.21 g/ml, respectively). Seventy percent of the cholesterol occurred in the chylomicrons and VLDL, although the LDL cholesterol was also elevated above normal levels. Agarose gel electrophoresis demonstrated a broadly migrating, lipid staining band between the prebeta and beta positions consistent with the accumulation of ß-VLDL (chylomicron and VLDL remnants) in the plasma.

The apoprotein profile on SDS-polyacrylamide gel electrophoresis was typical for harbor seals. Although no apoproteins were absent, we have recently discovered that the apoprotein E of harbor seals is about ten kilodaltons heavier than typical mammalian apoprotein E (e.g. 33 kilodaltons).

Although the etiology of this unusual condition in seals remains uncertain, the high cholesterol concentration in the VLDL fraction, large ratio of cholesterol to triglycerides, and presence of xanthomas are most analogous to Type III hypercholesterolemia, a heritable condition resulting from defective apoprotein E. There is evidence that this seal was the offspring of consanguineous mating between a female and one of her earlier male offspring. The female, which is still alive, has moderate hypercholesterolemia (483 mg/dl), but the male is normal. If the female and male are heterozygous for the defective apoprotein E, then their mating may have produced a homozygous condition for the defective apoprotein E, resulting in severe hypercholesterolemia and atherosclerosis in the seal that died.