Evidence mapPaperPMID 38415442Full record

ArticleCurrent medicinal chemistry2025

Evidence for the Involvement of Gene Regulation of Inflammatory Molecules in the Accumulation of Intracellular Cholesterol: The Mechanism of Foam Cell Formation in Atherosclerosis.

Vasily Nikolaevich Sukhorukov, Victoria Alexandrovna Khotina, Daria Dmitryevna Borodko, Mariam Bagheri Ekta, Yumiko Oishi, Andrey Vladimirovich Omelchenko, Kira Ivanovna Kolmychkova, Nikita G Nikiforov, Igor Alexandrovich Sobenin, Alexander Nikolaevich Orekhov

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Article in Current medicinal chemistry, 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
0.5field-weighted citation impact, top 38% 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

3 citing papers in PubMed, 2 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

10 authors at 4 institutions in 2 countries.

Vasily Nikolaevich SukhorukovLaboratory of Angiopathology, Institute of General Pathology and Pathophysiology, 125315, Moscow, Russia.
Victoria Alexandrovna KhotinaLaboratory of Angiopathology, Institute of General Pathology and Pathophysiology, 125315, Moscow, Russia.
Daria Dmitryevna BorodkoLaboratory of Angiopathology, Institute of General Pathology and Pathophysiology, 125315, Moscow, Russia.
Mariam Bagheri EktaLaboratory of Cellular and Molecular Pathology of Cardiovascular System, Petrovsky National Research Centre of Surgery, 119991, Moscow, Russia.
Yumiko OishiDepartment of Medical Biochemistry, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
Andrey Vladimirovich OmelchenkoLaboratory of Angiopathology, Institute of General Pathology and Pathophysiology, 125315, Moscow, Russia.
Kira Ivanovna KolmychkovaLaboratory of Angiopathology, Institute of General Pathology and Pathophysiology, 125315, Moscow, Russia.
Nikita G NikiforovLaboratory of Angiopathology, Institute of General Pathology and Pathophysiology, 125315, Moscow, Russia.
Igor Alexandrovich SobeninLaboratory of Angiopathology, Institute of General Pathology and Pathophysiology, 125315, Moscow, Russia.
Alexander Nikolaevich OrekhovLaboratory of Angiopathology, Institute of General Pathology and Pathophysiology, 125315, Moscow, Russia.
Research Institute of General Pathology and Pathophysiology, the Russian Academy of Medical Sciences · RUTokyo Medical and Dental University · JPInstitute of Experimental Cardiology · RURussian Scientific Center of Surgery · RU

Funding

Russian Science Foundation 23-45-00031
6 · The paper itself

Abstract

backgroundThe relationship between the cellular pro-inflammatory response and intracellular lipid accumulation in atherosclerosis is not sufficiently studied. Transcriptomic analysis is one way to establish such a relationship. Previously, we identified 10 potential key genes (IL-15, CXCL8, PERK, IL-7, IL-7R, DUSP1, TIGIT, F2RL1, TSPYL2, and ANXA1) involved in cholesterol accumulation in macrophages. It should be noted that all these genes do not directly participate in cholesterol metabolism, but encode molecules related to inflammation.

methodsIn this study, we conducted a knock-down of the 10 identified key genes using siRNA to determine their possible role in cholesterol accumulation in macrophages. To assess cholesterol accumulation, human monocyte-derived macrophages (MDM) were incubated with atherogenic LDL from patients with atherosclerosis. Cholesterol content was assessed by the enzymatic method. Differentially expressed genes were identified with DESeq2 analysis. Master genes were determined by the functional analysis.

resultsWe found that only 5 out of 10 genes (IL-15, PERK, IL-7, IL-7R, ANXA1) can affect intracellular lipid accumulation. Knock-down of the IL-15, PERK, and ANXA1 genes prevented lipid accumulation, while knock-down of the IL-7 and IL-7R genes led to increased intracellular lipid accumulation during incubation of MDM with atherogenic LDL. Seventeen overexpressed genes and 189 underexpressed genes were obtained in the DGE analysis, which allowed us to discover 20 upregulated and 86 downregulated metabolic pathways, a number of which are associated with chronic inflammation and insulin signaling. We also elucidated 13 master regulators of cholesterol accumulation that are immune response-associated genes.

conclusionThus, it was discovered that 5 inflammation-related master regulators may be involved in lipid accumulation in macrophages. Therefore, the pro-inflammatory response of macrophages may trigger foam cell formation rather than the other way around, where intracellular lipid accumulation causes an inflammatory response, as previously assumed.

Indexed as

AtherosclerosisCholesterolFoam CellsInflammationCells, CulturedGene Expression RegulationHumansMacrophagesRNA, Small InterferingCholesterolRNA, Small InterferingAtherosclerosisinflammationLDLlipid metabolismmacrophagestranscriptome analysis.

Identifiers

PMID38415442
OpenAlexW4392057611

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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.