Evidence map›Paper›PMID 20710028›Full record

ArticleThe Journal of biological chemistry2010

Oxidized cholesteryl esters and phospholipids in zebrafish larvae fed a high cholesterol diet: macrophage binding and activation.

Longhou Fang, Richard Harkewicz, Karsten Hartvigsen, Philipp Wiesner, Soo-Ho Choi, Felicidad Almazan, Jennifer Pattison, Elena Deer, Tiffany Sayaphupha, Edward A Dennis and 3 more

Abstract read
In one paragraph

Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.

0numbers the graph read from it
0cells of the map it votes in
54citing papers in PubMed
–field-weighted citation impact
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

54 citing papers in PubMed.

  1. Review
  2. Article
  3. Exploring Anti-inflammatory Compounds fromAnti-inflammatory & anti-allergy agents in medicinal chemistry · 2025
    Article
  4. Review
  5. Evaluating the Potential ofPharmaceuticals (Basel, Switzerland) · 2023
    Review
  6. Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Recent Application of Zebrafish Models in Atherosclerosis Research.Frontiers in cell and developmental biology · 2021
    Review
  13. Diversity of macrophage phenotypes and responses in atherosclerosis.Cellular and molecular life sciences : CMLS · 2020
    Review
  14. Review
  15. Review
  16. Article
  17. Review
  18. Article
  19. Anti-hypercholesterolemic Effect of Berbamine Isolated fromIranian journal of pharmaceutical research : IJPR · 2018
    Article
  20. Review
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

13 authors.

Longhou FangDepartment of Medicine, University of California, San Diego, La Jolla, California 92093, USA.
Richard Harkewicz
Karsten Hartvigsen
Philipp Wiesner
Soo-Ho Choi
Felicidad Almazan
Jennifer Pattison
Elena Deer
Tiffany Sayaphupha
Edward A Dennis
Joseph L Witztum
Sotirios Tsimikas
Yury I Miller

Funding

VIRAL MALIGNANCYP30CA023100 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DIANE M SIMEONE · 1985 to 2026
$124.9M
STEROL LIPIDSU54GM069338 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DENNIS, EDWARD A · 2003 to 2013
$72.2M
Transcriptional GenomicsP01HL088093 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI WITZTUM, JOSEPH L. · 2008 to 2018
$26.4M
Zebrafish models of vascular inflammation and atherosclerosisR01HL093767 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MILLER, YURY · 2009 to 2014
$2.5M
Early Forms of Oxidized LDL, TLRs and AtherosclerosisR01HL081862 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MILLER, YURY · 2006 to 2010
$2.1M
NCI NIH HHS P30 CA023100NCI NIH HHS P30 CA23100NHLBI NIH HHS HL081862NHLBI NIH HHS HL088093NHLBI NIH HHS HL093767NHLBI NIH HHS P01 HL088093NHLBI NIH HHS R01 HL081862NHLBI NIH HHS R01 HL093767NIGMS NIH HHS GM069338NIGMS NIH HHS U54 GM069338
6 · The paper itself

Abstract

A novel hypercholesterolemic zebrafish model has been developed to study early events of atherogenesis. This model utilizes optically transparent zebrafish larvae, fed a high cholesterol diet (HCD), to monitor processes of vascular inflammation in live animals. Because lipoprotein oxidation is an important factor in the development of atherosclerosis, in this study, we characterized the oxidized lipid milieu in HCD-fed zebrafish larvae. Using liquid chromatography-mass spectrometry, we show that feeding an HCD for only 2 weeks resulted in up to 70-fold increases in specific oxidized cholesteryl esters, identical to those present in human minimally oxidized LDL and in murine atherosclerotic lesions. The levels of oxidized phospholipids, such as 1-palmitoyl-2-oxovaleroyl-sn-glycero-3-phosphocholine, and of various lysophosphatidylcholines were also significantly elevated. Moreover, lipoproteins isolated from homogenates of HCD-fed larvae induced cell spreading as well as ERK1/2, Akt, and JNK phosphorylation in murine macrophages. Removal of apoB-containing lipoproteins from the zebrafish homogenates with an anti-human LDL antibody, as well as reducing lipid hydroperoxides with ebselen, resulted in inhibition of macrophage activation. The TLR4 deficiency in murine macrophages prevented their activation with zebrafish lipoproteins. Using biotinylated homogenates of HCD-fed larvae, we demonstrated that their components bound to murine macrophages, and this binding was effectively competed by minimally oxidized LDL but not by native LDL. These data provide evidence that molecular lipid determinants of proatherogenic macrophage phenotypes are present in large quantities in hypercholesterolemic zebrafish larvae and support the use of the HCD-fed zebrafish as a valuable model to study early events of atherogenesis.

Indexed as

ZebrafishAnimalsCell LineCholesterol, DietaryCholesterol EstersDietHumansLarvaMacrophagesMiceOxidation-ReductionPhospholipidsCholesterol, DietaryCholesterol EstersPhospholipids

Identifiers

PMID20710028
PMCPMC2952235

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.