Evidence map›Paper›PMID 24710030›Full record

ArticleCirculation2014

Inhibition of glycosphingolipid synthesis ameliorates atherosclerosis and arterial stiffness in apolipoprotein E-/- mice and rabbits fed a high-fat and -cholesterol diet.

Subroto Chatterjee, Djahida Bedja, Sumita Mishra, Christine Amuzie, Alberto Avolio, David A Kass, Dan Berkowitz, Mark Renehan

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Circulation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.

0numbers the graph read from it
0cells of the map it votes in
74citing papers in PubMed
7.5field-weighted citation impact, top 2% 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

74 citing papers in PubMed, 108 citations in OpenAlex.

  1. Trial
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  3. Glycyrrhizic Acid Alleviates Atherosclerosis inInternational journal of molecular sciences · 2026
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  14. Mouse Cardiovascular Imaging.Current protocols · 2024
    Review
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14 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 1 institution in 2 countries.

Subroto ChatterjeeFrom the Departments of Pediatrics (S.C., S.M., C.A., M.R.), Medicine (D. Bedja, D.A.K.), and Anesthesiology and Critical Care Medicine (D. Berkowitz), Johns Hopkins University School of Medicine, Baltimore, MD; and Australian School of Advanced Medicine, Macquarie University, Sydney, Australia (D. Bedja, A.A.). Schatte2@jhmi.edu.
Djahida BedjaFrom the Departments of Pediatrics (S.C., S.M., C.A., M.R.), Medicine (D. Bedja, D.A.K.), and Anesthesiology and Critical Care Medicine (D. Berkowitz), Johns Hopkins University School of Medicine, Baltimore, MD; and Australian School of Advanced Medicine, Macquarie University, Sydney, Australia (D. Bedja, A.A.).
Sumita MishraFrom the Departments of Pediatrics (S.C., S.M., C.A., M.R.), Medicine (D. Bedja, D.A.K.), and Anesthesiology and Critical Care Medicine (D. Berkowitz), Johns Hopkins University School of Medicine, Baltimore, MD; and Australian School of Advanced Medicine, Macquarie University, Sydney, Australia (D. Bedja, A.A.).
Christine AmuzieFrom the Departments of Pediatrics (S.C., S.M., C.A., M.R.), Medicine (D. Bedja, D.A.K.), and Anesthesiology and Critical Care Medicine (D. Berkowitz), Johns Hopkins University School of Medicine, Baltimore, MD; and Australian School of Advanced Medicine, Macquarie University, Sydney, Australia (D. Bedja, A.A.).
Alberto AvolioFrom the Departments of Pediatrics (S.C., S.M., C.A., M.R.), Medicine (D. Bedja, D.A.K.), and Anesthesiology and Critical Care Medicine (D. Berkowitz), Johns Hopkins University School of Medicine, Baltimore, MD; and Australian School of Advanced Medicine, Macquarie University, Sydney, Australia (D. Bedja, A.A.).
David A KassFrom the Departments of Pediatrics (S.C., S.M., C.A., M.R.), Medicine (D. Bedja, D.A.K.), and Anesthesiology and Critical Care Medicine (D. Berkowitz), Johns Hopkins University School of Medicine, Baltimore, MD; and Australian School of Advanced Medicine, Macquarie University, Sydney, Australia (D. Bedja, A.A.).
Dan BerkowitzFrom the Departments of Pediatrics (S.C., S.M., C.A., M.R.), Medicine (D. Bedja, D.A.K.), and Anesthesiology and Critical Care Medicine (D. Berkowitz), Johns Hopkins University School of Medicine, Baltimore, MD; and Australian School of Advanced Medicine, Macquarie University, Sydney, Australia (D. Bedja, A.A.).
Mark RenehanFrom the Departments of Pediatrics (S.C., S.M., C.A., M.R.), Medicine (D. Bedja, D.A.K.), and Anesthesiology and Critical Care Medicine (D. Berkowitz), Johns Hopkins University School of Medicine, Baltimore, MD; and Australian School of Advanced Medicine, Macquarie University, Sydney, Australia (D. Bedja, A.A.).
Johns Hopkins University · US

Funding

Shared Resource CoresP01HL107153 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI HART, GERALD WARREN · 2011 to 2017
$16.8M
JHU-UMD Diabetes Research CenterP30DK079637 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI WONDISFORD, FREDRIC E. · 2013 to 2017
$9.7M
NHLBI NIH HHS 3P01HL107153-03S1NHLBI NIH HHS P01 HL107153NHLBI NIH HHS P01HL107153NIDDK NIH HHS P30 DK079637
6 · The paper itself

Abstract

backgroundGlycosphingolipids, integral components of the cell membrane, have been shown to serve as messengers, transducing growth factor-initiated phenotypes. Here, we have examined whether inhibition of glycosphingolipid synthesis could ameliorate atherosclerosis and arterial stiffness in transgenic mice and rabbits. METHODS AND

resultsApolipoprotein E(-/-) mice (12 weeks of age; n=6) were fed regular chow or a Western diet (1.25% cholesterol, 2% fat). Mice were fed 5 or 10 mg/kg of an inhibitor of glycosphingolipid synthesis, D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (D-PDMP), solubilized in vehicle (5% Tween-80 in PBS); the placebo group received vehicle only. At 20 and 36 weeks of age, serial echocardiography was performed to measure aortic intima-media thickening. Aortic pulse-wave velocity measured vascular stiffness. Feeding mice a Western diet markedly increased aortic pulse-wave velocity, intima-media thickening, oxidized low-density lipoprotein, Ca(2+) deposits, and glucosylceramide and lactosylceramide synthase activity. These were dose-dependently decreased by feeding D-PDMP. In liver, D-PDMP decreased cholesterol and triglyceride levels by raising the expression of SREBP2, low-density lipoprotein receptor, HMGCo-A reductase, and the cholesterol efflux genes (eg, ABCG5, ABCG8). D-PDMP affected very-low-density lipoprotein catabolism by increasing the gene expression for lipoprotein lipase and very-low-density lipoprotein receptor. Rabbits fed a Western diet for 90 days had extensive atherosclerosis accompanied by a 17.5-fold increase in total cholesterol levels and a 3-fold increase in lactosylceramide levels. This was completely prevented by feeding D-PDMP.

conclusionsInhibition of glycosphingolipid synthesis ameliorates atherosclerosis and arterial stiffness in apolipoprotein E(-/-) mice and rabbits. Thus, inhibition of glycosphingolipid synthesis may be a novel approach to ameliorate atherosclerosis and arterial stiffness.

Indexed as

Diet, High-FatAnimalsAntigens, CDAortaApolipoproteins ECalciumCholesterol, DietaryCoronary Artery DiseaseDose-Response Relationship, DrugEnzyme InhibitorsGene Expression RegulationGlucosylceramidesGlycosphingolipidsHyperlipidemiasLactosylceramidesLipoproteins, LDLAntigens, CDApolipoproteins ECalciumCDw17 antigenCholesterol, DietaryEnzyme InhibitorsGlucosylceramidesGlycosphingolipidsLactosylceramidesLipoproteins, LDLMorpholinesoxidized low density lipoproteinRV 538atherosclerosisglycosphingolipidsmice, knockoutmolecular imaging

Identifiers

PMID24710030
PMCPMC4053506
OpenAlexW2089255055

What OpenQuestion holds

Textmetadata
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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.