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Cited by 60Per- and polyfluoroalkyl substances researchFluorine in Organic ChemistrySynthesis and properties of polymers

Plasma levels of per- and polyfluoroalkyl substances (PFAS) are associated with altered levels of proteins previously linked to inflammation, metabolism and cardiovascular disease

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Dunder, Linda, Salihovic, Samira, Lind, P. Monica, Elmståhl, Sölve, Lind, Lars·2023·Environment International
DOI 10.1016/j.envint.2023.107979
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Abstract

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) have been linked to immunotoxic and cardiometabolic effects in both experimental and epidemiological studies, but with conflicting results. AIM: The aim of the present study was to investigate potential associations between plasma PFAS levels and plasma levels of preselected proteomic biomarkers previously linked to inflammation, metabolism and cardiovascular disease. METHODS: Three PFAS (perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA) and perfluorohexane sulfonic acid (PFHxS)) were measured by non-targeted metabolomics and 249 proteomic biomarkers were measured by the proximity extension assay (PEA) in plasma from 2,342 individuals within the Epidemiology for Health (EpiHealth) study from Sweden (45-75 years old, 50.6 % men). RESULTS: After adjustment for age and sex, 92% of the significant associations between PFOS concentrations and proteins were inverse (p < 0.0002, Bonferroni-adjusted). The results were not as clear for PFOA and PFHxS, but still with 80% and 64 % of the significant associations with proteins being inverse. After adjustment for age, sex, smoking, education, exercise habits and alcohol consumption, levels of epidermal growth factor receptor (EGFR), and paraoxonase type 3 (PON3) remained positively associated with all three PFAS, while resistin (RETN) and urokinase plasminogen activator surface receptor (uPAR) showed inverse associations with all three PFAS. CONCLUSIONS: Our findings imply that PFAS exposure is cross-sectionally linked to altered levels of proteins previously linked to inflammation, metabolism and cardiovascular disease in middle-aged humans.

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  • Resistin and urokinase plasminogen activator (uPA) were inversely linked with all three analyzed PFAS compounds.

    “In addition, resistin (a hormone primarily produced by adipose tissue that plays a role in inflammation and insulin resistance) and urokinase plasminogen activator (uPA; a serine protease involved in tissue remodeling and cell migration) were inversely linked with all three PFAS compounds analyzed.”

    From Adverse health effects of PFAS (2025) · cites this paper as [7]

    Section 3.2 reports inverse associations between resistin (RETN) and all three PFAS. It reports the same for urokinase plasminogen activator surface receptor (uPAR), not urokinase plasminogen activator (uPA); these are different proteins. Page numbers were not provided in our copy. (LLM, conf=0.90)

    Experimental — accuracy not yet measured

  • After adjustment for confounders, the epidermal growth factor receptor and paraoxonase type 3 had a positive association with all three analyzed PFAS compounds (PFOS, PFOA, PFHxS).

    “including the receptor for epidermal growth factor (EGF; a protein involved in cell signaling pathways that control cell division and survival) and paraoxonase type 3 (a family of three enzymes known for their antioxidant and hydrolase activities) had a positive association with all three analyzed PFAS compounds7.”

    From Adverse health effects of PFAS (2025) · cites this paper as [7]

  • Dunder et al.'s analyses adjusted for confounders such as smoking, age, and alcohol.

    “After adjusting for confounders such as smoking, age, alcohol, and others, the following proteomic biomarkers were expressed”

    From Adverse health effects of PFAS (2025) · cites this paper as [7]

  • In Dunder et al.'s study, PFOS was inversely associated with specific proteomic biomarkers.

    “Their results revealed an inverse association between PFOS and specific proteomic biomarkers.”

    From Adverse health effects of PFAS (2025) · cites this paper as [7]

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Authors
Dunder, L., Salihovic, S., Lind, P. M., Elmståhl, S., & Lind, L.
Affiliations
  • Uppsala University (SE)
  • Lund University (SE)
Corresponding author
Dunder, Linda
ORCID
Venue
Environment International
Publisher
Elsevier BV
Published
2023-07
Volume
177
Pages
107979
ISSN
0160-4120 (ISSN-L)
DOI
10.1016/j.envint.2023.107979
OpenAlex
W4378070864
Cited by
60
References
2
Citations by year
2026: 18 · 2025: 24 · 2024: 16 · 2023: 2
FWCI
5.18
Type
journal article
Language
en
Open access
Licence
Locations
  • Environment International (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • KTH Publication Database DiVA (KTH Royal Institute of Technology) (submittedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Lund University Publications (Lund University) (submittedVersion)
Funders
  • Akademiska Sjukhuset
  • Vetenskapsrådet
Topics
  • Physical Sciences › Environmental Science › Environmental Chemistry › Per- and polyfluoroalkyl substances research
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Fluorine in Organic Chemistry
  • Physical Sciences › Materials Science › Polymers and Plastics › Synthesis and properties of polymers
Keywords
per- and polyfluoroalkyl substances, PFOS, perfluorooctanoic acid, PFHxS, inflammation, cardiometabolic disease, cardiovascular disease, epidermal growth factor receptor, resistin, uPAR, immunotoxicity, middle-aged adults
MeSH terms
Aged, Caprylates, Cardiovascular Diseases, Environmental Pollutants, Female, Fluorocarbons, Humans, Inflammation, Male, Middle Aged, Sulfonic Acids, Alkanesulfonic Acids, Proteomics

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