Evidence map›Paper›PMID 40701092›Full record

ArticleAtherosclerosis2025

Itaconate alleviates cholesterol burden via ABCA1 stabilization and cholesterol efflux.

Natalie E Hong, Anastasia M Ravodina, Courteney Asase, Huiyun Gao, Olga A Cherepanova, Andrei Maiseyeu

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Atherosclerosis, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. 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

6 authors.

Natalie E HongDepartment of Biomedical Engineering, School of Engineering, Case Western Reserve University, USA; Cardiovascular Research Institute, Case Western Reserve University School of Medicine, USA.
Anastasia M RavodinaDepartment of Medicine, School of Medicine, Case Western Reserve University, USA.
Courteney AsaseDepartment of Medicine, School of Medicine, Case Western Reserve University, USA.
Huiyun GaoDepartment of Medicine, School of Medicine, Case Western Reserve University, USA.
Olga A CherepanovaDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
Andrei MaiseyeuDepartment of Medicine, School of Medicine, Case Western Reserve University, USA; Department of Biomedical Engineering, Case Western Reserve University, USA. Electronic address: axm1079@case.edu.

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM007250 · CASE WESTERN RESERVE UNIVERSITY · 1985 to 2005
$7.3M
Medical Scientist Training Program at Case Western Reserve UniversityT32GM152319 · NIGMS · CASE WESTERN RESERVE UNIVERSITY · 2024 to 2025
$3.4M
Targets and targeting of immunometabolism in chronic PM2.5 exposureR01ES033670 · NIEHS · CASE WESTERN RESERVE UNIVERSITY · 2023 to 2025
$1.3M
NHLBI NIH HHS R01 HL130516NHLBI NIH HHS R01 HL150193NHLBI NIH HHS R01 HL155450NIEHS NIH HHS R01 ES033670NIGMS NIH HHS T32 GM007250NIGMS NIH HHS T32 GM152319
6 · The paper itself

Abstract

BACKGROUND AND

aimsItaconate (ITA) is a metabolite produced from the tricarboxylic acid cycle (TCA) that has been shown to regulate atherosclerotic plaque growth and induce stability via immunomodulation. However, lipid metabolism regulation by ITA is currently underexplored in atherosclerosis. Here, we take advantage of plaque-targeting ITA-conjugated nanoparticles (ITA-LNPs) to investigate the effects of ITA on regulating lipid metabolism in foam cells/macrophages in atherosclerosis via ABCA1 stabilization and increased triglyceride metabolism.

methodsApoe

resultsABCA1 was significantly upregulated with ITA-LNP treatment compared to Ctrl-LNP both in vivo and in vitro at the protein level, but not at the transcriptional level. ITA-LNPs were shown to prevent ABCA1 decay via the HO-1-calpain axis, resulting in significantly increased cholesterol efflux in macrophages. This was further confirmed in RAW 264.7 cells with a stable HO-1 knockdown. Additionally, ITA decreased lipid burden in conjunction with increased expression of Slc25a1 in ITA-LNP-treated BMDMs, suggesting enhanced fatty acid-derived citrate shuttling and increased fatty acid metabolism.

conclusionsITA-LNPs regulate lipid metabolism in atherosclerosis by inducing triglyceride catabolism and cholesterol efflux.

Indexed as

Aortic DiseasesAtherosclerosisATP Binding Cassette Transporter 1CholesterolSuccinatesAnimalsDiet, High-FatDisease Models, AnimalFoam CellsLipid MetabolismMacrophagesMaleMiceMice, Inbred C57BLMice, Knockout, ApoEPlaque, AtheroscleroticAbca1 protein, mouseATP Binding Cassette Transporter 1Cholesterolitaconic acidSuccinatesTriglycerides

Identifiers

PMID40701092
PMCPMC13152018

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.