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 indep endent risk factor that may be as important as elevated low-density li poproteins (LDLs) in coronary artery disease (CAD). Concentrations and distributions of lipids, apolipoprotein (ape) B, and apoA-I in the pl asma and lipoprotein subfractions of two groups of swine, one with fam ilial hypercholesterolemia (FHC) and the other with diet-induced hyper cholesterolemia (DHC), were examined. Normolipidemic (NL) animals serv ed as controls. All pigs carried the Lpb5 apoB mutation, which is know n to influence the formation of atherosclerotic lesions. Mean concentr ations 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, an d apoA-I in plasma lipoprotein subfractions were also examined. Compar ed with NL, FHC had fourfold and 4.7-fold increases in total cholester ol 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 cho lesterol/HDL-C ratio (14.4:1) and elevated triglyceride levels. DHC wa s 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 incr ease in apoA-I, and a normal triglyceride level. Thus FHC but not DHC exhibited a marked resemblance to familial combined hyperlipidemia, th e most common endogenous dyslipidemia in humans.