Composition and distribution of low density lipoprotein fractions in hyperapobetalipoproteinemia, normolipidemia, and familial hypercholesterolemia.

Hyperapobetalipoproteinemia is defined as the combination of a normal low density lipoprotein (LDL) cholesterol in the face of an increased LDL apolipoprotein B (apoB) protein. To examine the physical basis for the apparent disproportion between LDL cholesterol and apoB characteristic of this syndrome, we used density gradient ultracentrifugation to isolate LDL fractions from 10 normal subjects, from 20 patients with hyperapobetalipoproteinemia (10 normotriglyceridemic and 10 hypertriglyceridemic), and from 7 patients with familial hypercholesterolemia. In familial hypercholesterolemia, more LDL was in fraction 1--"light" LDL--and this LDL was relatively enriched in cholesterol and poor in protein. By contrast, it was fraction 2--"heavy" LDL--that differed in hyperapobetalipoproteinemia, being denser, depleted of cholesterol (particularly cholesteryl ester), and relatively enriched in apoB. These findings were more pronounced in the hypertriglyceridemic patients than in the normotriglyceridemic patients with hyperapobetalipoproteinemia. Thus this study confirms that considerable heterogeneity exists between LDL subfractions within individuals but, in addition, indicates there are also marked--and apparently characteristic--differences in LDL composition amongst normal subjects and patients with hyperapobetalipoproteinemia or familial hypercholesterolemia.