Evidence map›Paper›PMID 30002403›Full record

ArticleScientific reports2018

Systematic RNA-interference in primary human monocyte-derived macrophages: A high-throughput platform to study foam cell formation.

Gabriele Domschke, Fabian Linden, Lukas Pawig, Anna Hafner, Mohammadreza Akhavanpoor, Jürgen Reymann, Andreas O Doesch, Christian Erbel, Christian Weber, Hugo A Katus and 4 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
1.3field-weighted citation impact, top 21% 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

23 citing papers in PubMed, 38 citations in OpenAlex.

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  20. Quantitative Assessment of CMTM6 in the Tumor Microenvironment and Association with Response to PD-1 Pathway Blockade in Advanced-Stage Non-Small Cell Lung Cancer.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2019
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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

14 authors at 4 institutions in 4 countries.

Gabriele DomschkeInstitute of Human Genetics, University of Heidelberg, 69120, Heidelberg, Germany.
Fabian LindenDepartment of Cardiology, University of Heidelberg, 69120, Heidelberg, Germany.
Lukas PawigInstitute for Molecular Cardiovascular Research, RWTH Aachen University, University Clinic, 52074, Aachen, Germany.
Anna HafnerDepartment of Cardiology, University of Heidelberg, 69120, Heidelberg, Germany.
Mohammadreza AkhavanpoorDepartment of Cardiology, University of Heidelberg, 69120, Heidelberg, Germany.
Jürgen ReymannBioQuant, Heidelberg University, 69120, Heidelberg, Germany.
Andreas O DoeschDepartment of Cardiology, University of Heidelberg, 69120, Heidelberg, Germany.
Christian ErbelDepartment of Cardiology, University of Heidelberg, 69120, Heidelberg, Germany.
Christian WeberInstitute for Cardiovascular Prevention, LMU Munich and German Centre for Cardiovascular Research (DZHK), partner site Munich Heart Alliance, Munich, Germany.
Hugo A KatusDepartment of Cardiology, University of Heidelberg, 69120, Heidelberg, Germany.
Heidi NoelsInstitute for Molecular Cardiovascular Research, RWTH Aachen University, University Clinic, 52074, Aachen, Germany.ORCID 0000-0003-3053-6984
Holger ErfleBioQuant, Heidelberg University, 69120, Heidelberg, Germany.
Christian A GleissnerDepartment of Cardiology, University of Heidelberg, 69120, Heidelberg, Germany. christian.gleissner@med.uni-heidelberg.de.
Heiko RunzInstitute of Human Genetics, University of Heidelberg, 69120, Heidelberg, Germany. heiko.runz@gmail.com.
Heidelberg University · DERWTH Aachen University · DEBiogen (United States) · USMaastricht University · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Macrophage-derived foam cells are key regulators of atherogenesis. They accumulate in atherosclerotic plaques and support inflammatory processes by producing cytokines and chemokines. Identifying factors that regulate macrophage lipid uptake may reveal therapeutic targets for coronary artery disease (CAD). Here, we establish a high-throughput screening workflow to systematically identify genes that impact the uptake of DiI-labeled low-density lipoprotein (LDL) into monocyte-derived primary human macrophages. For this, monocytes isolated from peripheral blood were seeded onto 384-well plates, solid-phase transfected with siRNAs, differentiated in vitro into macrophages, and LDL-uptake per cell was measured by automated microscopy and quantitative image analysis. We applied this workflow to study how silencing of 89 genes impacts LDL-uptake into cells from 16 patients with CAD and 16 age-matched controls. Silencing of four novel genes (APOC1, CMTM6, FABP4, WBP5) reduced macrophage LDL-uptake. Additionally, knockdown of the chemokine receptor CXCR4 reduced LDL-uptake, most likely through a G-protein coupled mechanism that involves the CXCR4 ligand macrophage-induced factor (MIF), but is independent of CXCL12. We introduce a high-throughput strategy to systematically study gene function directly in primary CAD-patient cells. Our results propose a function for the MIF/CXCR4 signaling pathway, as well as several novel candidate genes impacting lipid uptake into human macrophages.

Indexed as

AdultAgedAged, 80 and overCell DifferentiationCoronary Artery DiseaseFoam CellsGene Knockdown TechniquesHumansIntramolecular OxidoreductasesLipid MetabolismLipoproteins, LDLMacrophage Migration-Inhibitory FactorsMaleMiddle AgedMolecular Targeted TherapyMonocytesCXCR4 protein, humanIntramolecular OxidoreductasesLipoproteins, LDLMacrophage Migration-Inhibitory FactorsMIF protein, humanReceptors, CXCR4RNA, Small Interfering

Identifiers

PMID30002403
PMCPMC6043567
OpenAlexW2870297137

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.