The metabolism of very low density and intermediate density lipoproteins in patients with familial hypercholesterolaemia

Abstract

The metabolism of apolipoprotein B (apoB) in very low density lipoprotein (VLDL) and intermediate density lipoprotein (IDL) was studied in normal subjects and in patients with familial hypercholesterolaemia (FH) after an intravenous injection of autologous VLDL labelled with 125I. There were no significant differences in half life, pool size and turnover rate (mg/kg/h) of VLDL-apoB between the normal subjects, the FH heterozygotes and the FH homozygotes. IDL-apoB metabolism in the FH patients differed significantly from that in the normal subjects. In the FH patients, the rise to the maximum of the specific activity curve was slower, the half life of the descending limb of the specific-activity curve was longer, the fractional rate of turnover was lower and the plasma concentration was higher than in the normals. The effect of cholestyramine on IDL-apoB metabolism in the normal subjects did not differ from that in the FH heterozygotes and homozygotes, though cholestyramine is known to stimulate hepatic uptake of low density lipoprotein (LDL) by the LDL receptor. It is suggested that in normal human subjects the LDL receptor makes some contribution to the hepatic uptake of IDL-apoB derived from VLDL, but that IDL uptake is mediated partly by a separate receptor that recognizes apolipoprotein E but not apoB.