Evidence mapPaperPMID 40207367Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2025

Inhibition of LXR Signaling in Human Foam Cells Impairs Macrophage-to-Endothelial Cell Cross Talk and Promotes Endothelial Cell Inflammation.

Damien Leleu, Thomas Pilot, Léa Mangin, Kevin Van Dongen, Lil Proukhnitzky, Damien Denimal, Maxime Samson, Aline Laubriet, Eric Steinmetz, Mickael Rialland and 6 more

Abstract read
In one paragraph

Article in Arteriosclerosis, thrombosis, and vascular biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Review
  3. 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

16 authors.

Damien LeleuCenter for Translational and Molecular Medecine (CTM), INSERM, UMR1231, Université Bourgogne Europe, Dijon, France (D.L., T.P., L.M., K.V.D., J.-P.P.B., T.G., C.T., D.M.).ORCID 0000-0003-3265-3201
Thomas PilotCenter for Translational and Molecular Medecine (CTM), INSERM, UMR1231, Université Bourgogne Europe, Dijon, France (D.L., T.P., L.M., K.V.D., J.-P.P.B., T.G., C.T., D.M.).
Léa ManginCenter for Translational and Molecular Medecine (CTM), INSERM, UMR1231, Université Bourgogne Europe, Dijon, France (D.L., T.P., L.M., K.V.D., J.-P.P.B., T.G., C.T., D.M.).
Kevin Van DongenCenter for Translational and Molecular Medecine (CTM), INSERM, UMR1231, Université Bourgogne Europe, Dijon, France (D.L., T.P., L.M., K.V.D., J.-P.P.B., T.G., C.T., D.M.).
Lil Proukhnitzky
Damien DenimalLipSTIC LabEx, Université Bourgogne-Franche compté, Dijon, France (D.L., T.P., L.M., K.V.D., J.-P.P.B., T.G., C.T., D.M.).ORCID 0000-0001-5454-954X
Maxime SamsonDepartment of Internal Medicine (M.S.), CHU Dijon Bourgogne, France.ORCID 0000-0002-6547-232X
Aline LaubrietDepartment of Cardiovascular Surgery (A.L., E.S.), CHU Dijon Bourgogne, France.
Eric SteinmetzDepartment of Cardiovascular Surgery (A.L., E.S.), CHU Dijon Bourgogne, France.
Emma Groetz
Jean-Paul Pais de BarrosCenter for Translational and Molecular Medecine (CTM), INSERM, UMR1231, Université Bourgogne Europe, Dijon, France (D.L., T.P., L.M., K.V.D., J.-P.P.B., T.G., C.T., D.M.).ORCID 0000-0002-5124-2283
Thomas GautierCenter for Translational and Molecular Medecine (CTM), INSERM, UMR1231, Université Bourgogne Europe, Dijon, France (D.L., T.P., L.M., K.V.D., J.-P.P.B., T.G., C.T., D.M.).ORCID 0000-0003-1119-7382
Charles ThomasCenter for Translational and Molecular Medecine (CTM), INSERM, UMR1231, Université Bourgogne Europe, Dijon, France (D.L., T.P., L.M., K.V.D., J.-P.P.B., T.G., C.T., D.M.).ORCID 0000-0001-9998-6698
David MassonCenter for Translational and Molecular Medecine (CTM), INSERM, UMR1231, Université Bourgogne Europe, Dijon, France (D.L., T.P., L.M., K.V.D., J.-P.P.B., T.G., C.T., D.M.).ORCID 0000-0003-1692-0699

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundDuring atherogenesis, macrophages turn into foam cells by engulfing lipids present within the atheroma plaques. The shift of foam cells toward proinflammatory or anti-inflammatory phenotypes, a critical step in disease progression, is still poorly understood. LXRs (liver X receptors) play a pivotal role in the macrophage response to lipid, promoting the expression of key genes of cholesterol efflux, mitigating intracellular cholesterol accumulation. LXRs also exert balanced actions on inflammation in human macrophages, displaying both proinflammatory and anti-inflammatory effects.

methodsOur study explored the role of LXRs in the functional response of human macrophage to lipid-rich plaque environment. We used primary human macrophages treated with atheroma plaque extracts and assessed the impact of pharmacological LXR inhibition by GSK2033 on cholesterol homeostasis and inflammatory response. Ultimately, we evaluated macrophage and endothelial cell cross talk by assessing the impact of macrophage-conditioned supernatants on the human endothelial cell.

resultsLXR inhibition by GSK2033 resulted in increased levels of cholesterol and oxysterols in human macrophages, alongside notable changes in the cholesterol ester profile. This was accompanied by heightened secretion of proinflammatory cytokines such as IL (interleukin)-6 and TNFα (tumor necrosis factor-α), despite a transcriptional repression of IL-1β. Conditioned media from GSK2033-treated macrophages more effectively activated ICAM-1 (intercellular adhesion molecule-1) and CCL2 (C-C motif ligand 2) expression in endothelial cells.

conclusionsOur findings illustrate the intricate relationship between LXR function, cholesterol metabolism, and inflammation in human macrophages. While LXR is required for the proper handling of plaque lipids by macrophages, the differential regulation of IL-1β versus IL-6/TNFα secretion by LXRs could be challenging for potential pharmacological interventions.

Indexed as

AtherosclerosisCell CommunicationFoam CellsHuman Umbilical Vein Endothelial CellsIndolesInflammationLiver X ReceptorsMacrophagesCells, CulturedCholesterolHumansInflammation MediatorsPlaque, AtheroscleroticSignal TransductionCholesterolIndolesInflammation MediatorsLiver X Receptorsatherosclerosisendothelial cellshomeostasisliver X receptorsmacrophages

Identifiers

PMID40207367
PMCPMC12094261

What Socratic holds

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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 Socratic graph.