Structure, Immunology, and Cell Reactivity of Low Density Lipoprotein from Umbilical Vein of a Newborn Type II Homozygote

In this report we compare the cord blood lipoproteins of a newborn boy homozygote who has low density lipoprotein (LDL) receptor-defective familial hypercholesterolemia (FH) with the lipoproteins from cord blood of normal newborns. Plasma LDL-cholesterol and apoprotein (Apo)B were 612 and 233 mg/dl (vs. 31±16 and 24±12 mg/dl, respectively, for normals, n = 21). LDL-cholesterol/ApoB ratio was 2.6 vs. 1.4±0.5. Levels of ApoA-I, ApoA-II, and HDL-cholesterol were similar to normal cord plasma. Thus, the lipoprotein abnormality is apparent at birth and is definitely present in LDL. Abnormalities in other lipoprotein, lipid, and in plasma apoprotein levels were not detected. On zonal ultracentrifugation, FH LDL was comprised of two populations (LDL_a and LDL_b), both faster floating than normal cord LDL (LDL_c). This difference was due to the larger diameters of the particles on electron microscopy (LDL_a = 276ű32 and LDL_b = 260ű38 vs. LDL_c = 237ű26, n = 200 each, mean±1 SD), and their higher contents of lipids relative to protein (86 and 82% vs. 74%, LDL_a, LDL_b, and LDL_c, respectively). More than 94% of the protein in both the FH and the normal preparations consisted of ApoB. FH LDL were more effective than control LDL in competing with ¹²⁵I-LDL (adult) for limiting amounts of anti-LDL antibodies in radioimmunoassay. FH LDL also competed more effectively for binding to LDL receptors on cultured fibroblasts at 4°C, and FH LDL also delivered more cholesterol into the cells. Cells grown in lipoprotein-deficient serum contained 44±2 μg cholesterol/mg cell protein, incubation of cells for 18 h at 37°C in 5 μg/ml FH LDL (protein) or in normal LDL raised cellular cholesterol levels to 75±2 and 60±2 μg/mg, respectively.