ETS variant transcription factor 6 enhances oxidized low-density lipoprotein-induced inflammatory response in atherosclerotic macrophages via activating NF-κB signaling
Open accessAbstract
Objectives: Macrophages play a critical role in atherosclerosis by contributing to plaque development, local inflammation, and thrombosis. Elucidation of the molecular cascades in atherosclerotic macrophages is important for preventing and treating atherosclerosis. This study aims to deepen the understanding of the mechanisms that regulate the function of aorta macrophage in atherosclerosis. Methods: In the current study, the expression and function of ETS variant transcription factor 6 (ETV6) in aorta macrophages in a mouse atherosclerosis model. Aorta macrophages were enriched by flow cytometry. ETV6 expression was analyzed by quantitative RT-PCR. The role of ETV6 in macrophage-mediated pro-inflammatory response was evaluated both in vitro and in vivo after ETV6 silencing. Results: A remarkable elevation of ETV6 in aorta macrophages of atherosclerotic mice was observed. In addition, in vitro analysis indicated that oxidized low-density lipoprotein (oxLDL) up-regulated ETV6 in macrophages via the NF-κB pathway. ETV6 silencing suppressed oxLDL-induced expression of IL-1β, IL-6, and TNF-α in macrophages in vitro. However, ETV6 silencing did not impact the uptake of either oxLDL or cholesterol by macrophages. Furthermore, ETV6 silencing suppressed oxLDL-induced activation of the NF-κB pathway in macrophages, as evidenced by less phosphorylation of IKKβ and NF-κB p65, more cytoplasmic IκBα, and lower nuclear NF-κB p65. Moreover, ETV6 silencing inhibited the production of IL-1β and TNF-α in aorta macrophages in vivo. Conclusion: ETV6 supports macrophage-mediated inflammation in atherosclerotic aortas. This is a novel mechanism regulating the pro-inflammatory activity of atherosclerotic macrophages.
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This epigenetic signature is also seen in macrophages in atherosclerosis models and adipose-associated macrophages, but this signature is not seen in DAM microglia.
“This epigenetic signature is also seen in macrophages in atherosclerosis models23 and adipose-associated macrophages24 but this signature is not seen in DAM microglia25.”
From APOE4/4 is linked to damaging lipid droplets in Alzheimer’s disease microglia (2024) · cites this paper as [23]
The Results section ('Elevation of ETV6 in aorta macrophages in ApoE−/− mice'; page unavailable) reports increased ETV6 expression in macrophages from an atherosclerosis model. The cited portion of the sentence concerns an epigenetic signature, but neither that section nor the passages retrieved by searching for epigenetic and chromatin terms identifies or measures one. The adipose-macrophage and DAM-microglia portions have separate citations and are not assessed here. (LLM, conf=0.72)
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APOE4/4 is linked to damaging lipid droplets in Alzheimer’s disease microglia
Haney, M. S., Pálovics, R., Munson, C. N., Long, C., Johansson, P. K., Yip, O., Dong, W., Rawat, E., West, E., Schlachetzki, J. C. M., et al. (2024) · Nature · doi:10.1038/s41586-024-07185-7 · Cited by 536 · see citing works
“This epigenetic signature is also seen in macrophages in atherosclerosis models 23 and adipose-associated macrophages 24 but this signature is not seen in DAM microglia 25 .”
- Authors
- Xiong, X., Yan, Z., Jiang, W., & Jiang, X.
- Affiliations
- Wuhan University (CN)
- Renmin Hospital of Wuhan University (CN)
- Corresponding author
- Xiong, Xiaofang
- Jiang, Xuejun
- Venue
- International Journal of Immunopathology and Pharmacology
- Publisher
- SAGE Publications
- Published
- 2022-03-19
- Volume
- 36
- Pages
- 20587384221076472-20587384221076472
- ISSN
- 0394-6320 (ISSN-L)
- 2058-7384
- PMC
- PMC8943319
- OpenAlex
- W4220955689
- Cited by
- 10
- References
- 0
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 2 · 2023: 2 · 2022: 2
- FWCI
- 0.67
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- International Journal of Immunopathology and Pharmacology (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Wuhan Municipal Health and Family Planning Commission Foundation (WE15A03)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Keywords
- ETV6, atherosclerosis, oxidized LDL, NF-κB signaling, macrophage inflammation, inflammatory cytokines, IL-1β, TNF-α, interleukin-6, IKKβ, IκBα, aorta
- MeSH terms
- ETS Translocation Variant 6 Protein, Animals, Inflammation, Lipoproteins, LDL, Macrophages, Repressor Proteins, NF-kappa B, Atherosclerosis, Proto-Oncogene Proteins c-ets, Mice
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