Evidence map›Paper›PMID 40728694›Full record

ArticleCardiovascular toxicology2025

Per- and Polyfluoroalkyl Substances (PFAS) Enhance Cholesterol Accumulation and Dysregulate Inflammatory Responses in Macrophages.

Jack C Connolly, Yasuhiro Ishihara, Emma Sawaya, Valerie Whitfield, Nicole Garrity, Rajveer Sohata, Mark Tsymbal, Alyssa Lundberg, Michele A La Merrill, Jamie C DeWitt and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cardiovascular toxicology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing 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

8 citing papers in PubMed.

  1. Review
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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

12 authors.

Jack C ConnollyCenter for Health and the Environment, University of California, Davis, CA, 95616, USA.
Yasuhiro IshiharaProgram of Biomedical Science, Graduate School of Integrated Sciences for Life, Hiroshima University, Hiroshima, 739-8521, Japan.
Emma SawayaCenter for Health and the Environment, University of California, Davis, CA, 95616, USA.
Valerie WhitfieldCenter for Health and the Environment, University of California, Davis, CA, 95616, USA.
Nicole GarrityCenter for Health and the Environment, University of California, Davis, CA, 95616, USA.
Rajveer SohataCenter for Health and the Environment, University of California, Davis, CA, 95616, USA.
Mark TsymbalCenter for Health and the Environment, University of California, Davis, CA, 95616, USA.
Alyssa LundbergCenter for Health and the Environment, University of California, Davis, CA, 95616, USA.
Michele A La MerrillDepartment of Environmental Toxicology, University of California, Davis, CA, 95616 , USA.
Jamie C DeWittDepartment of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR, 97331, USA.
Allison K EhrlichDepartment of Environmental Toxicology, University of California, Davis, CA, 95616 , USA.
Christoph F A VogelCenter for Health and the Environment, University of California, Davis, CA, 95616, USA. cfvogel@ucdavis.edu.ORCID 0000-0002-7561-4598

Funding

UC Davis Environmental Health Sciences Core CenterP30ES023513 · UNIVERSITY OF CALIFORNIA AT DAVIS · 2025 to 2025
$1.6M
Ah-Receptor as a central mediator of immunomodulation in the tumor microenvironment of breast cancerR01ES036338 · UNIVERSITY OF CALIFORNIA AT DAVIS · 2025 to 2025
$496k
NIEHS NIH HHS P30 ES023513NIEHS NIH HHS R01 ES036338NIEHS NIH HHS R01ES036338
6 · The paper itself

Abstract

Epidemiological studies and in vivo animal models have shown that exposure to PFAS can lead to cardiovascular toxicity and promote atherosclerosis. In this study, we explored the effects of PFOA and PFOS exposure on lipid accumulation in macrophages and analyzed critical markers of foam cell formation, which are early precursors of atherosclerotic lesions. Our results demonstrate that PFOS and PFOA enhance lipid and cholesterol accumulation in human U937-derived macrophages, which is characteristic of foam cells. PFOS and PFOA induced the activity of the peroxisome proliferator-activated receptor gamma (PPARγ) and treatment with a PPARγ antagonist partly reversed the accumulation of lipids after PFAS exposure. Furthermore, the results show that PFOS and PFOA activate (NF)-erythroid-derived 2 (E2)-related factor 2 (Nrf2) and induce markers of oxidative stress. Gene expression analysis revealed that mRNA levels of interleukin-1β (IL-1β) and plasminogen activator inhibitor-2 (PAI-2) were upregulated in a time- and concentration-dependent manner in PFOS- and PFOA-treated macrophages. The expression of other key atherosclerosis-related enzymes, including cytochrome P450 8B1 (CYP8B1) and lanosterol synthase (LSS), was downregulated, whereas the expression of cyclooxygenase 2 (COX-2) and aldo-keto reductase family 1 member C3 (AKR1C3) was induced by PFOS and PFOA. Additionally, elevated levels of matrix metalloproteinases (MMP)-1 and MMP-12 were found in PFOS- and PFOA-treated cells, which were associated with increased cell migration. Furthermore, PFOS and PFOA enhanced the expression of IL-1β when macrophages were activated; however, elevated levels of IL-6 and COX-2 in activated macrophages were repressed by PFOS and PFOA. Together, the findings indicate that PFAS exposure modifies immune responses and promotes lipid accumulation in macrophages, potentially contributing to foam cell and plaque formation in atherosclerosis.

Indexed as

Alkanesulfonic AcidsCaprylatesCholesterolFluorocarbonsFoam CellsInflammationInflammation MediatorsMacrophagesAtherosclerosisDose-Response Relationship, DrugHumansOxidative StressPPAR gammaSignal TransductionU937 CellsAlkanesulfonic AcidsCaprylatesCholesterolFluorocarbonsInflammation Mediatorsperfluorooctane sulfonic acidperfluorooctanoic acidPPAR gammaCardiovascular diseaseCytokinesFoam cellsLipidsMacrophagesPFASPPARSARS-CoV-2

Identifiers

PMID40728694
PMCPMC12432094

What Socratic 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 Socratic graph.