Small liver fenestrae may explain the susceptibility of rabbits to atherosclerosis

Rabbits fed cholesterol rapidly develop high serum cholesterol levels which lead to the development of atherosclerosis. This is related to the retention of cholesterol-rich chylomicron remnants in the circulation. In most animals, such as rats, chylomicron remnants are rapidly removed from the circulation by the liver. The first barrier to this removal is the fenestrated endothelium of liver sinusoids. Measurements made of a large number of sinusoidal fenestrae by scanning electron microscopy have shown the average diameters to be 89 nm in rats and 49 nm in rabbits. We postulate that the small size of endothelial fenestrae in the liver sinusoids of rabbits hinders the egress of chylomicron remnants from the sinusoidal blood, explaining the subsequent development of hypercholesterolemia and atherosclerosis.