title: Effects on lipoprotein subclasses of combined expression of human hepatic lipase and human apoB in transgenic rabbits.
abstract: 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.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors: Department of Genome Sciences, Lawrence Berkeley National Laboratory, University of California, Berkeley, USA.
authors: Manfredi
authors: M
authors: Rizzo
authors: John M
authors: JM
authors: Taylor
authors: Carlo M
authors: CM
authors: Barbagallo
authors: Kaspar
authors: K
authors: Berneis
authors: Patricia J
authors: PJ
authors: Blanche
authors: Ronald M
authors: RM
authors: Krauss
mesh_terms: D000821:Animal Feed; D000818:Animals; D030801:Animals, Genetically Modified; D001055:Apolipoproteins B / Q000235:genetics / Q000502:physiology*; D002499:Centrifugation, Density Gradient; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006801:Humans; D008049:Lipase / Q000235:genetics / Q000502:physiology*; D008077:Lipoproteins, LDL / Q000145:classification / Q000378:metabolism; D008970:Molecular Weight; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000502:physiology; D013045:Species Specificity; D013047:Specific Pathogen-Free Organisms; D014280:Triglycerides / Q000378:metabolism
chemical_list: D001055:Apolipoproteins B; D008077:Lipoproteins, LDL; D011993:Recombinant Fusion Proteins; D014280:Triglycerides; D008049:Lipase