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Titolo:
HEPATIC APO-E EXPRESSION IS REQUIRED FOR REMNANT LIPOPROTEIN CLEARANCE IN THE ABSENCE OF THE LOW-DENSITY-LIPOPROTEIN RECEPTOR
Autore:
LINTON MF; HASTY AH; BABAEV VR; FAZIO S;
Indirizzi:
VANDERBILT UNIV,SCH MED,DIV ENDOCRINOL,715 MED RES BLDG II NASHVILLE TN 37232 VANDERBILT UNIV,MED CTR,DEPT MED NASHVILLE TN 37232 VANDERBILT UNIV,MED CTR,DEPT PATHOL NASHVILLE TN 37232 VANDERBILT UNIV,MED CTR,DEPT PHARMACOL NASHVILLE TN 37232
Titolo Testata:
The Journal of clinical investigation
fascicolo: 8, volume: 101, anno: 1998,
pagine: 1726 - 1736
SICI:
0021-9738(1998)101:8<1726:HAEIRF>2.0.ZU;2-1
Fonte:
ISI
Lingua:
ENG
Soggetto:
BONE-MARROW TRANSPLANTATION; E-DEFICIENT MICE; HEPARAN-SULFATE PROTEOGLYCANS; APOLIPOPROTEIN-E; CHYLOMICRON REMNANTS; LDL-RECEPTOR; SEVERE HYPERCHOLESTEROLEMIA; TRANSGENIC MICE; KNOCKOUT MICE; IN-VIVO;
Keywords:
MACROPHAGES; BONE MARROW TRANSPLANTATION; GENE DELIVERY; DYSLIPIDEMIA; MOUSE MODELS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
42
Recensione:
Indirizzi per estratti:
Citazione:
M.F. Linton et al., "HEPATIC APO-E EXPRESSION IS REQUIRED FOR REMNANT LIPOPROTEIN CLEARANCE IN THE ABSENCE OF THE LOW-DENSITY-LIPOPROTEIN RECEPTOR", The Journal of clinical investigation, 101(8), 1998, pp. 1726-1736

Abstract

According to the secretion-capture model of remnant lipoprotein clearance, apo E secreted bg hepatocytes into the spate 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 (LBP), 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 thanin C57BL/6 controls. Immunocytochemistry of hepatic sections revealedabundant staining for apo E in the space of Disse, but no evidence ofreceptor-mediated endocytosis of remnant Lipoproteins. Transient expression of human LDLR in the livers of apo E(+/+)-->apo E(-/-)LDLR(-/-)mice by adenoviral gene transfer resulted in normalization of serum lipid levels and in the clearance of apo E-containing lipoproteins fromthe space of Disse, We conclude that whereas the LDLR efficiently clears remnant lipoproteins irrespective of the site of origin of apo E, endocytosis by the chylomicron remnant receptor (LRP) is absolutely dependent on hepatic expression of apo E. These data demonstrate in vivothe physiologic relevance of the apo]E secretion-capture mechanism inthe liver.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 27/11/20 alle ore 15:06:25