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Lipoproteins in blood plasma have been quantified and characterized in homozygous Watanabe-heritable hyperlipidemic (WHHL) rabbits, an animal model of human familial hypercholesterolemia. Like homozygous human hypercholesterolemics, WHHL rabbits have a severe deficiency of low density lipoprotein (LDL) receptors, a prolonged residence time for LDL, and an increased absolute rate of LDL catabolism. Although lipoproteins containing apolipoprotein B in WHHL rabbits are enriched in cholesteryl esters, their LDL as well as intermediate density lipoproteins (IDL) and very low density lipoproteins (VLDL) also contain a substantial amount of triglycerides and they consistently exhibit hypertriglyceridemia as well as hypercholesterolemia. The cholesteryl esters accumulating in lipoproteins of WHHL rabbits are rich in cholesteryl linoleate and appear to be produced almost exclusively by lecithin-cholesterol acyltransferase. Levels of apolipoprotein B-100 are elevated in VLDL and IDL as well as in LDL of WHHL rabbits and only trace amounts of apolipoprotein B-48 are present. Plasma levels of apolipoprotein E are also substantially increased, and VLDL and IDL are enriched in this protein. The accumulation of lipoproteins with the expected characteristics of remnants of hepatogenous triglyceride-rich lipoproteins contrasts with the efficient hepatic clearance of chylomicron remnants in WHHL rabbits.

Concentration and composition of lipoproteins in blood plasma of the WHHL rabbit. An animal model of human familial hypercholesterolemia.