Hepatic apo E expression is required for remnant lipoprotein clearance in the absence of the low density lipoprotein receptor

The Journal of Clinical Investigation
M F LintonS Fazio

Abstract

According to the secretion-capture model of remnant lipoprotein clearance, apo E secreted by hepatocytes into the space of Disse serves to enrich the remnants with a ligand for receptor-mediated lipoprotein endocytosis. Current evidence supports a two-receptor model of lipoprotein removal, in which apo E-containing remnants bind either the low density lipoprotein receptor (LDLR) or the LDLR-related protein (LRP). Recently, we demonstrated that reconstitution of apo E(-/-) mice with apo E(+/+) marrow results in normalization of plasma lipoprotein levels, indicating that hepatic expression of apo E is not required for remnant clearance and calling into question the relevance of the secretion-capture mechanism. To dissect the relative contributions of LDLR and LRP to the cellular catabolism of remnant lipoproteins by the hepatocyte, bone marrow transplantation (BMT) was used to reconstitute macrophage expression of apo E in mice that were null for expression of both apo E and the LDLR. Reconstitution of macrophage apo E in apo E(-/-)/LDLR(-/-) mice had no effect on serum lipid and lipoprotein concentrations, although it produced plasma apo E levels up to 16-fold higher than in C57BL/6 controls. Immunocytochemistry of hepatic secti...Continue Reading

References

Jul 1, 1991·The Journal of Clinical Investigation·M F LintonS G Young
Aug 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·R C KowalM S Brown
Nov 1, 1986·The Journal of Clinical Investigation·E J SchaeferH B Brewer
Jun 1, 1982·Proceedings of the National Academy of Sciences of the United States of America·T KitaR J Havel
Dec 1, 1981·Proceedings of the National Academy of Sciences of the United States of America·S K BasuJ L Goldstein
May 9, 1995·Proceedings of the National Academy of Sciences of the United States of America·T E WillnowJ Herz
Aug 1, 1995·The Journal of Clinical Investigation·W A BoisvertL K Curtiss
May 9, 1995·Proceedings of the National Academy of Sciences of the United States of America·J HerzR J Havel
May 10, 1994·Proceedings of the National Academy of Sciences of the United States of America·S IshibashiM S Brown
Sep 1, 1993·The Journal of Clinical Investigation·S FazioS C Rall
Apr 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·J Herz, R D Gerard
Oct 1, 1995·Current Opinion in Lipidology·R J Havel
Apr 29, 1997·Proceedings of the National Academy of Sciences of the United States of America·S FazioM F Linton

❮ Previous
Next ❯

Citations

Apr 14, 2005·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Kirsty GreenowDipak P Ramji
Jan 16, 2004·Experimental Gerontology·S N HilmerD G Le Couteur
Jan 11, 2001·Trends in Cardiovascular Medicine·S FazioL L Swift
Jul 6, 2000·Current Opinion in Lipidology·L K Curtiss, W A Boisvert
May 16, 2001·Current Opinion in Lipidology·J Heeren, U Beisiegel
Aug 16, 2012·Current Opinion in Lipidology·Robert L Raffai
Feb 13, 2010·Arteriosclerosis, Thrombosis, and Vascular Biology·Patricia G YanceySergio Fazio
Oct 28, 1998·The Journal of Clinical Investigation·M M VéniantS G Young
Jun 8, 1999·The Journal of Clinical Investigation·C KnouffN Maeda
Dec 10, 2013·BioMed Research International·Elaine Regina Delicato de AlmeidaMaria Angelica Ehara Watanabe
Oct 16, 1999·Proceedings of the National Academy of Sciences of the United States of America·T AraiA R Tall
Dec 26, 2001·Proceedings of the National Academy of Sciences of the United States of America·Charles W JoyceSilvia Santamarina-Fojo
Aug 13, 2013·Journal of Microbiology, Immunology, and Infection = Wei Mian Yu Gan Ran Za Zhi·Pan FuChuan-Qing Wang
Jun 17, 2009·The American Journal of Pathology·Elizabeth K YoungDaniel L Sparks
Jan 14, 2005·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Arndt F SchillingMichael Amling
Apr 10, 2007·The Journal of Nutritional Biochemistry·Kimberly R CoenenAlyssa H Hasty
Aug 10, 2000·Molecular Therapy : the Journal of the American Society of Gene Therapy·K TsukamotoD J Rader
Aug 18, 2004·Journal of Colloid and Interface Science·Justin LegleiterTomasz Kowalewski
Aug 17, 2005·Atherosclerosis·Marnie L GruenAlyssa H Hasty
Sep 28, 2005·Journal of Lipid Research·Elyisha A HannimanChristopher J Sinal
Apr 27, 1999·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·M MassimiS K Erickson
Feb 17, 2007·Circulation Research·Cheryl D OvertonSergio Fazio
Dec 11, 1999·Arteriosclerosis, Thrombosis, and Vascular Biology·K W van DijkM H Hofker
Aug 11, 2000·Arteriosclerosis, Thrombosis, and Vascular Biology·L K Curtiss
Mar 29, 2008·Arteriosclerosis, Thrombosis, and Vascular Biology·Michael AltenburgNobuyo Maeda
Oct 16, 2004·International Journal of Obesity and Related Metabolic Disorders : Journal of the International Association for the Study of Obesity·M R M Oliveira, R C Maranhão
Oct 5, 2018·Journal of Personalized Medicine·Eftaxia-Konstantina ValantiDespina Sanoudou

❮ Previous
Next ❯

Related Concepts

Related Feeds

ApoE Phenotypes

Apolipoprotein E (APOE) is a protein involved in fat metabolism and associated with the pathogenesis of Alzheimer's disease and cardiovascular disease. Here is the latest research on APOE phenotypes.

ApoE, Lipids & Cholesterol

Serum cholesterol, triglycerides, apolipoprotein B (APOB)-containing lipoproteins (very low-density lipoprotein (VLDL), immediate-density lipoprotein (IDL), and low-density lipoprotein (LDL), lipoprotein A (LPA)) and the total cholesterol/high-density lipoprotein (HDL) cholesterol ratio are all connected in diseases. Here is the latest research.