Evidence map›Paper›PMID 25201834›Full record

ArticleJournal of lipid research2014

Disruption of ldlr causes increased LDL-c and vascular lipid accumulation in a zebrafish model of hypercholesterolemia.

Elizabeth A O'Hare, Xiaochun Wang, May E Montasser, Yen-Pei C Chang, Braxton D Mitchell, Norann A Zaghloul

Open access · hybridAbstract read
In one paragraph

Article in Journal of lipid research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
0.8field-weighted citation impact, top 31% 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

26 citing papers in PubMed, 45 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Zebrafish ApoB-Containing Lipoprotein Metabolism: A Closer Look.Arteriosclerosis, thrombosis, and vascular biology · 2024
    Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Review
  16. Studies in Zebrafish Demonstrate ThatFrontiers in cardiovascular medicine · 2020
    Article
  17. Article
  18. Xuezhitong capsule, an extract ofAnnals of translational medicine · 2019
    Article
  19. Article
  20. Article
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

6 authors at 1 institution in 1 country.

Elizabeth A O'HareDepartment of Medicine, Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, Baltimore, MD.
Xiaochun WangDepartment of Medicine, Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, Baltimore, MD.
May E MontasserDepartment of Medicine, Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, Baltimore, MD.
Yen-Pei C ChangDepartment of Medicine, Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, Baltimore, MD.
Braxton D MitchellDepartment of Medicine, Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, Baltimore, MD.
Norann A ZaghloulDepartment of Medicine, Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, Baltimore, MD.
University of Maryland, Baltimore · US

Funding

Research BaseP30DK072488 · NIDDK · UNIVERSITY OF MARYLAND BALTIMORE · PI MITCHELL, BRAXTON D, TAYLOR, SIMEON I. · 2005 to 2019
$17.3M
Identification and Functional characterization of a gene influencing LDL-C on 5qR01HL121007 · NHLBI · UNIVERSITY OF MARYLAND BALTIMORE · PI MITCHELL, BRAXTON D · 2014 to 2017
$3.1M
The Biology of Exercise, Metabolism and AgingT32AG000219 · NIA · UNIVERSITY OF MARYLAND BALTIMORE · PI RYAN, ALICE S. · 1992 to 2014
$2.4M
Basal body regulation of glucose homeostasisR01DK102001 · NIDDK · UNIVERSITY OF MARYLAND BALTIMORE · PI MITCHELL, BRAXTON D · 2014 to 2018
$1.7M
Ciliary Regulation of Notch-based PhenotypesK01DK092402 · NIDDK · UNIVERSITY OF MARYLAND BALTIMORE · PI ZAGHLOUL, NORANN AMIR · 2011 to 2013
$338k
NHLBI NIH HHS R01 HL121007NIA NIH HHS T32 AG000219NIA NIH HHS T32-AG000219NIDDK NIH HHS K01 DK092402NIDDK NIH HHS K01DK092402NIDDK NIH HHS P30 DK072488NIDDK NIH HHS R01 DK102001
6 · The paper itself

Abstract

Hyperlipidemia and arterial cholesterol accumulation are primary causes of cardiovascular events. Monogenic forms of hyperlipidemia and recent genome-wide association studies indicate that genetics plays an important role. Zebrafish are a useful model for studying the genetic susceptibility to hyperlipidemia owing to conservation of many components of lipoprotein metabolism, including those related to LDL, ease of genetic manipulation, and in vivo observation of lipid transport and vascular calcification. We sought to develop a genetic model for lipid metabolism in zebrafish, capitalizing on one well-understood player in LDL cholesterol (LDL-c) transport, the LDL receptor (ldlr), and an established in vivo model of hypercholesterolemia. We report that morpholinos targeted against the gene encoding ldlr effectively suppressed its expression in embryos during the first 8 days of development. The ldlr morphants exhibited increased LDL-c levels that were exacerbated by feeding a high cholesterol diet. Increased LDL-c was ameliorated in morphants upon treatment with atorvastatin. Furthermore, we observed significant vascular and liver lipid accumulation, vascular leakage, and plaque oxidation in ldlr-deficient embryos. Finally, upon transcript analysis of several cholesterol-regulating genes, we observed changes similar to those seen in mammalian systems, suggesting that cholesterol regulation may be conserved in zebrafish. Taken together, these observations indicate conservation of ldlr function in zebrafish and demonstrate the utility of transient gene knockdown in embryos as a genetic model for hyperlipidemia.

Indexed as

ZebrafishAnimalsAtorvastatinBase SequenceBlood VesselsCholesterol, LDLDisease Models, AnimalEmbryo, NonmammalianGene Expression RegulationGene Knockdown TechniquesHepatomegalyHeptanoic AcidsHypercholesterolemiaLiverMolecular Sequence DataMorpholinosAtorvastatinCholesterol, LDLHeptanoic AcidsMorpholinosPyrrolesReceptors, LDLatherosclerosislow density lipoproteinlow density lipoprotein cholesterollow density lipoprotein receptor

Identifiers

PMID25201834
PMCPMC4617127
OpenAlexW2034672127

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.