Published online before print April 11, 2002, doi: 10.1161/01.ATV.0000018304.30943.06
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© 2002 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Normal Production Rate of Apolipoprotein B in LDL Receptor–Deficient Mice
From the Department of Medicine, University of Pennsylvania, Philadelphia.
Correspondence to John S. Millar, PhD, University of Pennsylvania, Department of Medicine, 644 BRB II/III, 421 Curie Blvd, Philadelphia, PA 19104. E-mail jsmillar{at}mail.med.upenn.edu
Abstract— The low density lipoprotein (LDL) receptor is well known for its role in mediating the removal of apolipoprotein B (apoB)-containing lipoproteins from plasma. Results from in vitro studies in primary mouse hepatocytes suggest that the LDL receptor may also have a role in the regulation of very low density lipoprotein (VLDL) production. We conducted in vivo experiments using LDLR-/-, LDLR+/-, and wild-type mice (LDLR indicates LDL receptor gene) in which the production rate of VLDL was measured after the injection of [35S]methionine and the lipase inhibitor Triton WR1339. Despite the fact that LDLR-/- mice had a 3.7-fold higher total cholesterol level and a 2.1-fold higher triglyceride level than those of the wild-type mice, there was no difference in the production rate of VLDL triglyceride or VLDL apoB between these groups of animals. Experiments were also conducted in apobec1-/- mice, which make only apoB-100, the form of apoB that binds to the LDL receptor. Interestingly, the apobec1-/- mice had a significantly higher production rate of apoB than did the wild-type mice. However, despite significant differences in total cholesterol and triglyceride levels, there was no difference in the production rate of total or VLDL triglyceride or VLDL apoB between LDLR-/- and LDLR+/- mice on an apobec1-/- background. These results indicate that the LDL receptor has no effect on the production rate of VLDL triglyceride or apoB in vivo in mice.
Key Words: triglycerides • very low density lipoproteins • familial hypercholesterolemia • Triton WR1339 • apobec1
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