Ordinarily, HDL1, a fraction of HDL enriched in
apoE, is a minor fraction of plasma, but in human subjects and experimental animals eating diets high in fat and
cholesterol and in patients with
homozygous familial hypercholesterolemia (HFH) or
CETP deficiency, HDL1 (or HDLc) concentrations in plasma are increased. However, little is known about the structures, compositions and metabolic sources of HDL1 in HFH patients. To obtain HDL1 for the study, we surveyed several fractions in the HDL density range for
apoE by SDS-PAGE. The ratio of
apoE to apoAI in the HDL (d = 1.063-1.21 g/ml) of 8 HFH patients was 0.14 +/- 0.03 compared to 0.03 +/- 0.005 in a control group of 8 normolipidemic subjects (P less than 0.001) suggesting that an
apoE-rich fraction indeed was present in increased amounts.
ApoE/apoAI ratios of
lipoproteins of the density range 1.050-1.090 were even higher at 1.5 and 2.0 in 2 patients compared to 0.4 +/- 0.1 in controls, indicating that this density fraction may be particularly enriched with
apoE-rich
lipoproteins. By contrast, d = 1.020-1.050 g/ml and d greater than 1.090 fractions contained very little
apoE. Therefore, we further characterized the d = 1.050-1.090 g/ml
lipoproteins of HFH patients and controls. Fractionation of an d = 1.050-1.090 fraction by
concanavalin-A chromatography (CONA) yielded an unbound
apoE-rich fraction that contained
apoE, apoAI and
apoC but no
apoB, and a bound
LDL-like fraction that contained mostly
apoB-100, as determined by SDS-PAGE and by solid phase immunoassays, containing
monoclonal antibodies directed against
apoB,
apoE and apoAI. The
apoE/apoAI ratio of the CONA unbound fraction of HFH patients was greater, and the fraction also contained more free
cholesterol and
phospholipids than the fraction of control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)