Lipoprotein clearance mechanisms in LDL receptor-deficient "Apo-B48-only" and "Apo-B100-only" mice.
The role of the low density lipoprotein receptor (LDLR) in the clearance of apo-B48-containing lipoproteins and the role of the LDLR-related protein (LRP) in the removal of apo-B100-containing lipoproteins have not been clearly defined. To address these issues, we characterized LDLR-deficient mice homozygous for an "apo-B48-only" allele, an "apo-B100-only" allele, or a wild-type apo-B allele (Ldlr-/- Apob48/48, Ldlr-/-Apob100/100, and Ldlr-/-Apob+/+, respectively). The plasma apo-B48 and LDL cholesterol levels were higher in Ldlr-/-Apob48/48 mice than in Apob48/48 mice, indicating that the LDL receptor plays a significant role in the removal of apo-B48-containing lipoproteins. To examine the role of the LRP in the clearance of apo-B100-containing lipoproteins, we blocked hepatic LRP function in Ldlr-/-Apob100/100 mice by adenoviral-mediated expression of the receptor-associated protein (RAP). RAP expression did not change apo-B100 levels in Ldlr-/-Apob100/100 mice. In contrast, RAP expression caused a striking increase in plasma apo-B48 levels in Apob48/48 and Ldlr-/-Apob48/48 mice. These data imply that LRP is important for the clearance of apo-B48-containing lipoproteins but plays no significant role in the clearance of apo-B100-containing lipoproteins.
Véniant
M M
MM
Gladstone Institute of Cardiovascular Disease, San Francisco, California 94141-9100, USA. mveniant@gladstone.ucsf.edu
Zlot
C H
CH
Walzem
R L
RL
Pierotti
V
V
Driscoll
R
R
Dichek
D
D
Herz
J
J
Young
S G
SG
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D053299:Apolipoprotein B-100; D053283:Apolipoprotein B-48; D001055:Apolipoproteins B / Q000235:genetics / Q000378:metabolism*; D008078:Cholesterol, LDL / Q000097:blood; D018014:Gene Transfer Techniques; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D008657:Metabolic Clearance Rate; D051379:Mice; D008817:Mice, Mutant Strains; D010316:Particle Size; D011863:Radioimmunoassay; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D011973:Receptors, LDL / Q000172:deficiency / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism
D053299:Apolipoprotein B-100; D053283:Apolipoprotein B-48; D001055:Apolipoproteins B; D008078:Cholesterol, LDL; D008055:Lipids; D008074:Lipoproteins; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D011971:Receptors, Immunologic; D011973:Receptors, LDL; D011994:Recombinant Proteins