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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:141.)
© 2004 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Effects on Lipoprotein Subclasses of Combined Expression of Human Hepatic Lipase and Human apoB in Transgenic Rabbits

Manfredi Rizzo; John M. Taylor; Carlo M. Barbagallo; Kaspar Berneis; Patricia J. Blanche; Ronald M. Krauss

From the Department of Genome Sciences (M.R., P.J.B., R.M.K.), Lawrence Berkeley National Laboratory, University of California, Berkeley; the Department of Clinical Medicine and Emerging Diseases (M.R., C.M.B.), University of Palermo, Italy; the Gladstone Institute of Cardiovascular Disease (J.M.T.), University of California, San Francisco; and the Department of Internal Medicine (K.B.), University Hospital Bruderholz, Switzerland.

Correspondence to Ronald M. Krauss, MD, Children’s Hospital Oakland Research Institute (CHORI), 5700 Martin Luther King, Jr. Way, Oakland, CA 94609-1673. 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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