FAMILIAL AND DIET-INDUCED HYPERCHOLESTEROLEMIA IN SWINE - LIPID, APO-B, AND APOA-I CONCENTRATIONS AND DISTRIBUTIONS IN PLASMA AND LIPOPROTEIN SUBFRACTIONS

Low levels of high-density lipoproteins (HDLs) may constitute an independent risk factor that may be as important as elevated low-density lipoproteins (LDLs) in coronary artery disease (CAD). Concentrations and distributions of lipids, apolipoprotein (ape) B, and apoA-I in the plasma and lipoprotein subfractions of two groups of swine, one with familial hypercholesterolemia (FHC) and the other with diet-induced hypercholesterolemia (DHC), were examined. Normolipidemic (NL) animals served as controls. All pigs carried the Lpb5 apoB mutation, which is known to influence the formation of atherosclerotic lesions. Mean concentrations of serum total cholesterol in NL, DHC, and FHC were 80.0+/-9.3, 774.3+/-54.5, and 316.5+/-36.1 mg/dL, respectively; HDL cholesterol (HDL-C), 33.5+/-1.9, 137.0+/-9.9, and 22.3+/-2.2 mg/dL; triglycerides, 33.0+/-16.3, 40.3+/-11.7, and 56.8+/-7.2 mg/dL; apoB, 35.7+/-3.1, 142.0+/-4.8, and 169.3+/-13.9 mg/dL; and apoA-I, 62.4+/-9.3, 170.9+/-6.9, and 42.6+/-4.8 mg/dL. The distributions of total cholesterol, apoB, and apoA-I in plasma lipoprotein subfractions were also examined. Compared with NL, FHC had fourfold and 4.7-fold increases in total cholesterol and apoB, respectively, distributed in the lower densities (d<1.043 g/mL), and low HDL-C and apoA-I levels, resulting in a high total cholesterol/HDL-C ratio (14.4:1) and elevated triglyceride levels. DHC was characterized by 10-fold and fourfold increases in total cholesterol and apoB, respectively, resulting in an LDL particle highly enriched in cholesterol, a fourfold increase of HDL-C, an almost threefold increase in apoA-I, and a normal triglyceride level. Thus FHC but not DHC exhibited a marked resemblance to familial combined hyperlipidemia, the most common endogenous dyslipidemia in humans.