Evidence map›Paper›PMID 41948895›Full record

ArticleMediators of inflammation2026

The IRE1α Pathway Links Endoplasmic Reticulum Stress to Atherosclerosis-Related Inflammation and Lipid Accumulation.

Mariam Bagheri Ekta, Natalia Elizova, Stanislav Antonov, Alexander Orekhov, Vasily Sukhorukov

Abstract read
In one paragraph

Article in Mediators of inflammation, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

5 authors.

Mariam Bagheri EktaLaboratory of Cellular and Molecular Pathology of the Cardiovascular System, Petrovsky National Research Center of Surgery (Formerly Russian Scientific Center of Surgery), Abrikosovsky Lane 2, Moscow, 119991, Russia.ORCID https://orcid.org/0000-0001-7952-1068
Natalia ElizovaLaboratory of Cellular and Molecular Pathology of the Cardiovascular System, Petrovsky National Research Center of Surgery (Formerly Russian Scientific Center of Surgery), Abrikosovsky Lane 2, Moscow, 119991, Russia.
Stanislav AntonovLaboratory of Cellular and Molecular Pathology of the Cardiovascular System, Petrovsky National Research Center of Surgery (Formerly Russian Scientific Center of Surgery), Abrikosovsky Lane 2, Moscow, 119991, Russia.ORCID https://orcid.org/0000-0002-6866-7077
Alexander OrekhovLaboratory of Molecular Genetic Modeling of Inflammaging, Institute of General Pathology and Pathophysiology, Baltiyskaya Street 8, Moscow, 125315, Russia, niiopp.ru.ORCID https://orcid.org/0000-0002-3318-4681
Vasily SukhorukovLaboratory of Molecular Genetic Modeling of Inflammaging, Institute of General Pathology and Pathophysiology, Baltiyskaya Street 8, Moscow, 125315, Russia, niiopp.ru.ORCID https://orcid.org/0000-0002-0312-3773

Funding

Russian Science Foundation # 25-15-00483
6 · The paper itself

Abstract

Endoplasmic reticulum stress (ER stress) is closely related to the pathogenesis of atherosclerosis through various mechanisms, including inflammatory responses and foam cell formation. However, the mechanisms by which ER stress contributes to atherosclerosis require further elucidation. In this study, we investigate the impact of the inositol-requiring enzyme 1 alpha (IRE1α) arm of the unfolded protein response (UPR) in the expression of inflammatory cytokines in monocytes and intracellular lipid accumulation in macrophages, which play a crucial role in the immune response associated with atherosclerosis. We created an IRE1α knockout (KO) THP-1 monocytic cell line using the CRISPR/Cas9 gene-editing technology and subsequently differentiated these cells into macrophages. We conducted a comparative analysis of IRE1α KO cells and control THP-1 cells, focusing on several parameters: morphological features, lipopolysaccharide (LPS)-induced proinflammatory cytokine responses, specifically interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor (TNF) α measured by quantitative real-time PCR (qPCR) and enzyme-linked immunosorbent assay (ELISA), as well as intracellular cholesterol accumulation and the expression levels of CD36 and ABCA1 genes following exposure to low-density lipoproteins (LDLs) derived from patients with atherosclerosis. Our findings demonstrate that IRE1α KO resulted in significant reduction of TNF, IL-1β, and IL-6 expression following LPS stimulation (p  < 0.05). ELISA confirmed significantly reduced cytokine secretion in IRE1α KO monocytes compared to controls. Furthermore, IRE1α deficiency impaired the cellular response to atherogenic LDL, preventing lipid-induced upregulation of scavenger receptor CD36 and cholesterol efflux transporter ABCA1. Thus, IRE1α serves as a critical regulator of both inflammatory cytokine expression and lipid metabolism in THP-1 cells, highlighting its potential as a therapeutic target for inflammatory diseases and atherosclerosis. Targeting IRE1α could offer new strategies to address inflammation and lipid dysregulation in cardiovascular diseases.

Indexed as

AtherosclerosisEndoplasmic Reticulum StressEndoribonucleasesInflammationProtein Serine-Threonine KinasesCholesterolEnzyme-Linked Immunosorbent AssayHumansInterleukin-1betaInterleukin-6Lipid MetabolismLipopolysaccharidesLipoproteins, LDLMacrophagesMonocytesTHP-1 CellsCholesterolEndoribonucleasesERN1 protein, humanInterleukin-1betaInterleukin-6LipopolysaccharidesLipoproteins, LDLProtein Serine-Threonine KinasesTumor Necrosis Factor-alphaatherosclerosisCRISPR/Cas9inflammationIRE1αmacrophagesunfolded protein response

Identifiers

PMID41948895
PMCPMC13058818

What Socratic holds

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LicenceCC BY
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Registered trials

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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.