Evidence map›Paper›PMID 41240326›Full record

ArticleChemical research in toxicology2026

Per- and Polyfluoroalkyl Substances Induce Cardiotoxicity and Alter Protein Profiles of Extracellular Matrix, Metabolism, and Mitochondrial Function in Human Cardiomyocytes.

Wenhao Zhang, Zeyu Wang, Olivia Reid, Frank Harris, Kun Man, Matthew Wang, Stephanie Li, Lawrence C Armand, Alicia Lane, Gayatri Patel and 6 more

Abstract read
In one paragraph

Article in Chemical research in toxicology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
  4. 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

16 authors.

Wenhao ZhangDepartment of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, Georgia 30322, United States.
Zeyu WangSchool of Chemistry and Biochemistry and the Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia 30332, United States.
Olivia ReidDepartment of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, Georgia 30322, United States.
Frank HarrisDepartment of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, Georgia 30322, United States.
Kun ManDepartment of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, Georgia 30322, United States.
Matthew WangDepartment of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, Georgia 30322, United States.
Stephanie LiDepartment of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, Georgia 30322, United States.
Lawrence C ArmandDepartment of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, Georgia 30322, United States.
Alicia LaneDepartment of Cell Biology, Emory University School of Medicine, Atlanta, Georgia 30322, United States.
Gayatri PatelWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia 30332, United States.
Victor FaundezDepartment of Cell Biology, Emory University School of Medicine, Atlanta, Georgia 30322, United States.
Yuhong DuDepartment of Pharmacology and Chemical Biology, Emory University School of Medicine, Atlanta, Georgia 30322, United States.
Ronghu WuSchool of Chemistry and Biochemistry and the Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia 30332, United States.ORCID 0000-0001-9493-9462
Lou Ann BrownDepartment of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, Georgia 30322, United States.
W Michael CaudleGangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, Georgia 30322, United States.
Chunhui XuDepartment of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, Georgia 30322, United States.ORCID 0000-0003-1748-0648

Funding

Pilot Project ProgramP30ES019776 · NIEHS · EMORY UNIVERSITY · PI William Michael Caudle · 2013 to 2026
$22.6M
Alcohol-induced cardiac injury and repair in human induced pluripotent stem cell modelR01AA028527 · NIAAA · EMORY UNIVERSITY · PI XU, CHUNHUI · 2021 to 2025
$1.8M
High-throughput assessment of chemotherapy-induced cardiotoxicity in 3D human cardiomyocytesR21CA285254 · NCI · EMORY UNIVERSITY · PI XU, CHUNHUI · 2024 to 2024
$402k
NCI NIH HHS R21 CA285254NIAAA NIH HHS R01 AA028527NIEHS NIH HHS P30 ES019776
6 · The paper itself

Abstract

Per- and polyfluoroalkyl substances (PFAS), common environmental contaminants, can cause cardiotoxic effects particularly during fetal development. However, the effect of combined PFAS exposure, which more closely reflects real-world environmental conditions, remains poorly understood. In this study, human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were exposed to three common PFAS compounds─perfluorohexanesulfonic acid (PFHxS), perfluorooctanoic acid (PFOA), and perfluorodecanoic acid (PFDA)─individually or in combination (20-200 μM; consistent with serum levels reported in occupationally exposed populations). Compared with single compounds, combined PFAS exposure induced synergistic cytotoxicity, significantly reducing hiPSC-CM viability after 5 or 10 days. Sublethal combined exposure for 10 days altered mitochondrial membrane potential and mitochondrial content in a dose-dependent manner and shifted cysteine metabolism, potentially reflecting adaptation to oxidative challenge. After 14 days, combined PFAS increased vimentin, a fibroblast marker, and reduced NKX2.5, α-actinin, and cardiac troponin T, key markers of cardiomyocytes, as detected by immunocytochemistry. Proteomics further showed enrichment of pathways in extracellular matrix organization, cholesterol metabolism, and antioxidant defense, as well as downregulation of mitochondrial proteins. Consistent with changes in protein profiles related to oxidative stress and bioenergetic impairment, exposure of hiPSC-CMs to combined PFAS also increased the level of mitochondrial superoxide, reduced ATP content, and decreased cellular respiration. Together, these data demonstrate that PFAS mixtures drive mitochondrial dysfunction, oxidative stress, metabolic changes, and extracellular matrix remodeling in hiPSC-CMs, underscoring the importance of evaluating PFAS mixtures to better understand cardiac risks from environmental exposure.

Indexed as

CaprylatesCardiotoxicityDecanoic AcidsEnvironmental PollutantsExtracellular MatrixFluorocarbonsMitochondriaMyocytes, CardiacCells, CulturedCell SurvivalDose-Response Relationship, DrugHumansInduced Pluripotent Stem CellsMembrane Potential, MitochondrialCaprylatesDecanoic AcidsEnvironmental PollutantsFluorocarbonsperfluorodecanoic acidperfluorooctanoic acid

Identifiers

PMID41240326
PMCPMC12820961

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.