Evidence map›Paper›PMID 10359567›Full record

ArticleThe Journal of clinical investigation1999

Apo E structure determines VLDL clearance and atherosclerosis risk in mice.

C Knouff, M E Hinsdale, H Mezdour, M K Altenburg, M Watanabe, S H Quarfordt, P M Sullivan, N Maeda

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of clinical investigation, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 179 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
179citing papers in PubMed, 1 pooled it
2.2field-weighted citation impact, top 12% 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

179 citing papers in PubMed, 1 synthesis or guideline pooled it, 341 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Alzheimer's Disease Risk Factor APOE4 Exerts Dimorphic Effects on Female Bone.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  4. FASEB bioAdvances · 2026
    Article
  5. Article
  6. iScience · 2026
    Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Proteomic and metabolic profiling revealsbioRxiv : the preprint server for biology · 2025
    Article
  15. Article
  16. Article
  17. Article
  18. Review
  19. Article
  20. Article

119 more citing papers are in PubMed but not listed here.

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

8 authors at 4 institutions in 3 countries.

C KnouffDepartment of Pathology and Laboratory Medicine, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina 27599-7525, USA.
M E Hinsdale
H Mezdour
M K Altenburg
M Watanabe
S H Quarfordt
P M Sullivan
N Maeda
University of North Carolina at Chapel Hill · USDuke University Hospital · USHokkaido University · JPInstitut Pasteur de Lille · FR

Funding

Virology Research Program (Program 4)P30CA016086 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Deborah F. Tate · 1985 to 2026
$201.5M
APOLIPOROTEIN GENES AND ATHEROGENESISR01HL042630 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI MAEDA, NOBUYO · 1989 to 2017
$4.9M
APOLIPOPROTEIN GENES AND ATHEROGENESIS IN ANIMALSR37HL042630 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI MAEDA, NOBUYO · 1998 to 2007
$3.4M
MODELS OF ATHEROSCLEROSIS BY TARGETED GENE DUPLICATIONK01RR000111 · NCRR · UNIVERSITY OF NORTH CAROLINA CHAPEL HILL · PI HINSDALE, MYRON E · 1995 to 1999
–
NCI NIH HHS P30 CA016086NCRR NIH HHS RR-00111NHLBI NIH HHS HL-42630NHLBI NIH HHS R01 HL042630NHLBI NIH HHS R37 HL042630
6 · The paper itself

Abstract

We have generated mice expressing the human apo E4 isoform in place of the endogenous murine apo E protein and have compared them with mice expressing the human apo E3 isoform. Plasma lipid and apolipoprotein levels in the mice expressing only the apo E4 isoform (4/4) did not differ significantly from those in mice with the apo E3 isoform (3/3) on chow and were equally elevated in response to increased lipid and cholesterol in their diet. However, on all diets tested, the 4/4 mice had approximately twice the amount of cholesterol, apo E, and apo B-48 in their VLDL as did 3/3 mice. The 4/4 VLDL competed with human LDL for binding to the human LDL receptor slightly better than 3/3 VLDL, but the VLDL clearance rate in 4/4 mice was half that in 3/3 mice. On an atherogenic diet, there was a trend toward greater atherosclerotic plaque size in 4/4 mice compared with 3/3 mice. These data, together with our earlier observations in wild-type and human APOE*2-replacement mice, demonstrate a direct and highly significant correlation between VLDL clearance rate and mean atherosclerotic plaque size. Therefore, differences solely in apo E protein structure are sufficient to cause alterations in VLDL residence time and atherosclerosis risk in mice.

Indexed as

AnimalsAortaApolipoprotein E2Apolipoprotein E3Apolipoprotein E4Apolipoproteins EArteriosclerosisHumansLipoproteins, VLDLMiceMice, Inbred C57BLRisk FactorsApolipoprotein E2Apolipoprotein E3Apolipoprotein E4Apolipoproteins ELipoproteins, VLDL

Identifiers

PMID10359567
PMCPMC408371
OpenAlexW1979536020

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.