Evidence map›Paper›PMID 22383685›Full record

ArticleJournal of lipid research2012

ApoE promotes hepatic selective uptake but not RCT due to increased ABCA1-mediated cholesterol efflux to plasma.

Wijtske Annema, Arne Dikkers, Jan Freark de Boer, Thomas Gautier, Patrick C N Rensen, Daniel J Rader, Uwe J F Tietge

Open access · hybridAbstract read
In one paragraph

Article in Journal of lipid research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed, 1 pooled it
4.1field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

15 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.

  1. Pooled it
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  3. Review
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  5. Article
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  7. Article
  8. Article
  9. Article
  10. New developments in selective cholesteryl ester uptake.Current opinion in lipidology · 2013
    Review
  11. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 6 institutions in 3 countries.

Wijtske AnnemaDepartment of Pediatrics, Center for Liver, Digestive, and Metabolic Diseases, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Top Institute Food and Nutrition, Wageningen, The Netherlands.
Arne DikkersDepartment of Pediatrics, Center for Liver, Digestive, and Metabolic Diseases, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Jan Freark de BoerDepartment of Pediatrics, Center for Liver, Digestive, and Metabolic Diseases, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Thomas GautierINSERM UMR866 Lipides, Nutrition, Cancer, Faculté de Médecine, Dijon, France.
Patrick C N RensenDepartment of General Internal Medicine, Endocrinology, and Metabolic Diseases, Leiden University Medical Center, Leiden, The Netherlands; and.
Daniel J RaderInstitute for Translational Medicine and Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, PA.
Uwe J F TietgeDepartment of Pediatrics, Center for Liver, Digestive, and Metabolic Diseases, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Top Institute Food and Nutrition, Wageningen, The Netherlands. Electronic address: u_tietge@yahoo.com.
TiFN · NLCentre de recherche Translationnelle en Médecine moléculaire · FRLeiden University Medical Center · NLTranslational Therapeutics (United States) · USUniversity Medical Center Groningen · NLUniversity of Groningen · NL

Funding

VECTOR COREP01HL059407 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI LIMBERIS, MARIA P. · 1999 to 2019
$35.6M
TISSUE CULTURE CORE LABORATORYP01HL022633 · NHLBI · MCP HAHNEMANN UNIVERSITY · PI LUND-KATZ, SISSEL · 1985 to 2013
$26.1M
NHLBI NIH HHS HL022633NHLBI NIH HHS HL059407NHLBI NIH HHS P01 HL022633NHLBI NIH HHS P01 HL059407
6 · The paper itself

Abstract

ApoE plays an important role in lipoprotein metabolism. This study investigated the effects of adenovirus-mediated human apoE overexpression (AdhApoE3) on sterol metabolism and in vivo reverse cholesterol transport (RCT). In wild-type mice, AdhApoE3 resulted in decreased HDL cholesterol levels and a shift toward larger HDL in plasma, whereas hepatic cholesterol content increased (P < 0.05). These effects were dependent on scavenger receptor class B type I (SR-BI) as confirmed using SR-BI-deficient mice. Kinetic studies demonstrated increased plasma HDL cholesteryl ester catabolic rates (P < 0.05) and higher hepatic selective uptake of HDL cholesteryl esters in AdhApoE3-injected wild-type mice (P < 0.01). However, biliary and fecal sterol output as well as in vivo macrophage-to-feces RCT studied with (3)H-cholesterol-loaded mouse macrophage foam cells remained unchanged upon human apoE overexpression. Similar results were obtained using hApoE3 overexpression in human CETP transgenic mice. However, blocking ABCA1-mediated cholesterol efflux from hepatocytes in AdhApoE3-injected mice using probucol increased biliary cholesterol secretion (P < 0.05), fecal neutral sterol excretion (P < 0.05), and in vivo RCT (P < 0.01), specifically within neutral sterols. These combined data demonstrate that systemic apoE overexpression increases i) SR-BI-mediated selective uptake into the liver and ii) ABCA1-mediated efflux of RCT-relevant cholesterol from hepatocytes back to the plasma compartment, thereby resulting in unchanged fecal mass sterol excretion and overall in vivo RCT.

Indexed as

AnimalsApolipoprotein E3ATP Binding Cassette Transporter 1ATP-Binding Cassette TransportersBiliary TractBiological TransportCD36 AntigensCholesterolCholesterol, HDLFecesHepatocytesHumansLiverMacrophagesMiceMice, Inbred C57BLABCA1 protein, humanApolipoprotein E3ATP Binding Cassette Transporter 1ATP-Binding Cassette TransportersCD36 AntigensCholesterolCholesterol, HDLProbucol

Identifiers

PMID22383685
PMCPMC3329392
OpenAlexW2066632683

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.