Effects on lipoprotein subclasses of combined expression of human hepatic lipase and human apoB in transgenic rabbits

Objective—The effects of combined expression of human hepatic lipase (HL) and human apolipoprotein B (apoB) on low-density lipoprotein (LDL) subclasses were examined in rabbits, a species naturally deficient in HL activity. Methods and Results—In apoB-transgenic rabbit plasma, 80% of the protein was found in the 1.006- to 1.050-g/mL fraction. Gradient gel electrophoresis (GGE) of this fraction revealed two distinct species, designated large and small LDL. A denser fraction (d 1.050 to 1.063 g/mL) contained small LDL as well as another discrete LDL subspecies, designated very small LDL. Expression of HL resulted in reductions in protein concentrations in the 1.006- to 1.050-g/mL density-gradient subfractions containing large (6.5 4.1 versus 32.6 12.0 mg/dL, P 0.005) and small LDL (59.6 17.4 versus 204.3 50.3 mg/dL, P 0.002). A concomitant small but not significant increase in protein concentration in the denser LDL fraction (48.0 28.2 versus 44.6 18.2 mg/dL) was due primarily to an increase in very small LDL (25.9 3.1 versus 9.6 5.4% of total LDL GGE densitometric area, P 0.002). Conclusion—These findings support a direct role for HL in regulating total plasma LDL concentrations as well as in the production of smaller, denser LDL from larger, more buoyant precursors.