Evidence map›Paper›PMID 37920458›Full record

ArticleFrontiers in immunology2023

GM-CSF-activated STAT5A regulates macrophage functions and inflammation in atherosclerosis.

Jan Nagenborg, Han Jin, Adele V Ruder, Lieve Temmerman, Barend Mees, Casper Schalkwijk, Daniel Müller-Klieser, Thorsten Berg, Pieter Goossens, Marjo M P C Donners and 1 more

Open access · goldAbstract read
In one paragraph

Article in Frontiers in immunology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
4.1field-weighted citation impact, top 5% 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

13 citing papers in PubMed, 18 citations in OpenAlex.

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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

11 authors at 2 institutions in 2 countries.

Jan NagenborgDepartment of Pathology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Center (UMC), Maastricht, Netherlands.
Han JinDepartment of Pathology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Center (UMC), Maastricht, Netherlands.
Adele V RuderDepartment of Pathology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Center (UMC), Maastricht, Netherlands.
Lieve TemmermanDepartment of Pathology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Center (UMC), Maastricht, Netherlands.
Barend MeesDepartment of Pathology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Center (UMC), Maastricht, Netherlands.
Casper SchalkwijkCardiovascular Research Institute Maastricht (CARIM), University Maastricht, Maastricht, Netherlands.
Daniel Müller-KlieserInstitute for Organic Chemistry, Faculty of Chemistry and Mineralogy, Leipzig, Germany.
Thorsten BergInstitute for Organic Chemistry, Faculty of Chemistry and Mineralogy, Leipzig, Germany.
Pieter GoossensDepartment of Pathology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Center (UMC), Maastricht, Netherlands.
Marjo M P C DonnersDepartment of Pathology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Center (UMC), Maastricht, Netherlands.
Erik A L BiessenDepartment of Pathology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Center (UMC), Maastricht, Netherlands.
Maastricht University · NLLeipzig University · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Introduction: Inhibition of STAT5 was recently reported to reduce murine atherosclerosis. However, the role of STAT5 isoforms, and more in particular STAT5A in macrophages in the context of human atherosclerosis remains unknown. Methods and results: Here, we demonstrate reciprocal expression regulation of STAT5A and STAT5B in human atherosclerotic lesions. The former was highly upregulated in ruptured over stable plaque and correlated with macrophage presence, a finding that was corroborated by the high chromosomal accessibility of STAT5A but not B gene in plaque macrophages. Phosphorylated STAT5 correlated with macrophages confirming its activation status. As macrophage STAT5 is activated by GM-CSF, we studied the effects of its silencing in GM-CSF differentiated human macrophages. STAT5A knockdown blunted the immune response, phagocytosis, cholesterol metabolism, and augmented apoptosis terms on transcriptional levels. These changes could partially be confirmed at functional level, with significant increases in apoptosis and decreases in lipid uptake and IL-6, IL-8, and TNFa cytokine secretion after STAT5A knockdown. Finally, inhibition of general and isoform A specific STAT5 significantly reduced the secretion of TNFa, IL-8 and IL-10 in ex vivo tissue slices of advanced human atherosclerotic plaques. Discussion: In summary, we identify STAT5A as an important determinant of macrophage functions and inflammation in the context of atherosclerosis and show its promise as therapeutic target in human atherosclerotic plaque inflammation.

Indexed as

AtherosclerosisGranulocyte-Macrophage Colony-Stimulating FactorAnimalsHumansInflammationInterleukin-8MacrophagesMiceSignal TransductionSTAT5 Transcription FactorTrans-ActivatorsTumor Suppressor ProteinsGranulocyte-Macrophage Colony-Stimulating FactorInterleukin-8STAT5A protein, humanSTAT5 Transcription FactorTrans-ActivatorsTumor Suppressor ProteinsatherosclerosisGM-CSFinflammationmacrophageSTAT5ASTAT5B

Identifiers

PMID37920458
PMCPMC10619680
OpenAlexW4387742161

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.