on November 13, 2003
Published online before print November 13, 2003, doi: 10.1161/01.ATV.0000107027.73816.ce
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Submitted on August 6, 2003
Accepted on November 3, 2003
Effects on Lipoprotein Subclasses of Combined Expression of Human Hepatic Lipase and Human apoB in Transgenic Rabbits
Manfredi Rizzo ;
* To whom correspondence should be addressed. E-mail: rmkrauss{at}lbl.gov.
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.
Key words: hepatic lipase • apoB • LDL • transgene • rabbit • density gradient ultracentrifugation
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