Evidence map›Paper›PMID 41365366›Full record

ArticleToxicology and applied pharmacology2026

Exposure to a PFAS mixture alters cholesterol lipoprotein subfractions and induces a foam cell-like aortic macrophage expression profile in hyperlipidemic LDLr

Katherine Roth, Zhao Yang, Manisha Agarwal, Katherine Gurdziel, Michael C Petriello

Abstract read
In one paragraph

Article in Toxicology and applied pharmacology, 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. 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

5 authors.

Katherine RothInstitute of Environmental Health Sciences, Wayne State University, Detroit, MI 48202, USA.
Zhao YangInstitute of Environmental Health Sciences, Wayne State University, Detroit, MI 48202, USA.
Manisha AgarwalDepartment of Pharmacology, School of Medicine, Wayne State University, Detroit, MI 48202, USA.
Katherine GurdzielGenomic Sciences Core, Wayne State University, Detroit, MI, USA.
Michael C PetrielloInstitute of Environmental Health Sciences, Wayne State University, Detroit, MI 48202, USA; Department of Pharmacology, School of Medicine, Wayne State University, Detroit, MI 48202, USA. Electronic address: Michael.petriello@wayne.edu.

Funding

Translational Research Support CoreP30ES036084 · NIEHS · WAYNE STATE UNIVERSITY · PI Carrie Leach · 2024 to 2026
$5.2M
PFAS accelerate atherosclerosis through modulation of bile acid metabolismR01ES034407 · NIEHS · WAYNE STATE UNIVERSITY · PI Michael Curtis Petriello · 2023 to 2026
$2.3M
Exposure to PFAS mixture induces atherosclerosis via modulation of bile acid transportF32ES034638 · NIEHS · WAYNE STATE UNIVERSITY · PI ROTH, KATHERINE · 2023 to 2024
$151k
NIEHS NIH HHS F32 ES034638NIEHS NIH HHS P30 ES036084NIEHS NIH HHS R01 ES034407
6 · The paper itself

Abstract

Per- and polyfluoroalkyl substances (PFAS) have been associated with elevated cholesterol, a clinically-relevant risk factor for atherosclerosis. Macrophages are key mediators of atherosclerosis progression through their polarization to various subsets including inflammatory macrophages and foam cells. However, studies examining impacts of PFAS on macrophages in the context of atherosclerosis are lacking. Here, we investigate the impact of PFAS mixtures on cholesterol subfractions and transcriptional profiling of aortic macrophages during early atherosclerosis. Male low density lipoprotein receptor (Ldlr) deficient mice were fed an atherogenic diet and exposed via their drinking water to a mixture of 5 PFAS (i.e., PFOA, PFOS, PFNA, PFHxS, and GenX), each at a concentration of 2 mg/L, for 7 weeks. Circulating cholesterol subfractions and subclasses were analyzed, and aortic macrophages were isolated using immuno-magnetic beads for RNA-sequencing. Total circulating cholesterol was significantly elevated by 10 % following PFAS exposure which was predominately due to a 25 % increase in intermediate-density lipoprotein (IDL). The densest subfraction of low-density lipoprotein, LDL7, also increased by 206 %. RNA sequencing of aortic macrophages revealed PFAS downregulated 389 and upregulated 593 genes; many related to lipid metabolism and foam cell development. Specifically, expression of inflammatory mediators chemokine (C-X-C motif) ligand 2 (Cxcl2) and chemokine (C-X-C motif) ligand 17 (Cxcl17) were significantly increased due to PFAS (2.4 log2 fold change and 10.4 log2 FC respectively) and levels of lipid metabolism and transport genes fatty acid binding protein 4 (Fabp4) and fatty acid synthase (Fasn) were similarly increased (3 log2 FC and 5.2 log2 FC respectively). This work provides additional mechanistic information related to PFAS-mediated acceleration of atherosclerosis.

Indexed as

AortaAtherosclerosisCholesterolFluorocarbonsFoam CellsHyperlipidemiasLipoproteinsMacrophagesReceptors, LDLAnimalsMaleMiceMice, Inbred C57BLMice, KnockoutCholesterolFluorocarbonsLipoproteinsReceptors, LDLAtherosclerosisCardiometabolic diseaseCholesterolHyperlipidemiaMacrophagePer- and polyfluoroalkyl substancesPFAS toxicity

Identifiers

PMID41365366
PMCPMC13141778

What Socratic holds

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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.