Cited by 210Per- and polyfluoroalkyl substances researchFluorine in Organic ChemistrySynthesis and properties of polymers

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Exposure to Perfluoroalkyl Chemicals and Cardiovascular Disease: Experimental and Epidemiological Evidence

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Meneguzzi, Alessandra, Fava, Cristiano, Castelli, Marco, Minuz, Pietro·2021·Frontiers in Endocrinology

DOI 10.3389/fendo.2021.706352PMC PMC8298860

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Abstract

Polyfluoro- and perfluoro–alkyl substances (PFAS) are organic chemicals extensively used worldwide for industry and consumer products. Due to their chemical stability, PFAS represent a major cause of environmental pollution. PFAS accumulate in animal and human blood and tissues exerting their toxicity. We performed a review of the epidemiological studies exploring the relationship between exposure to PFAS and thromboembolic cardiovascular disease. An increase in cardiovascular disease or death related to PFAS exposure has been reported from cross-sectional and longitudinal observational studies with evidence concerning the relation with early vascular lesions and atherosclerosis. Several studies indicate an alteration in lipid and glucose metabolism disorders and increased blood pressure as a possible link with cardiovascular thromboembolic events. We also examined the recent evidence indicating that legacy and new PFAS can be incorporated in platelet cell membranes giving a solid rationale to the observed increase risk of cardiovascular events in the populations exposed to PFAS by directly promoting thrombus formation. Exposure to PFAS has been related to altered plasma membrane fluidity and associated with altered calcium signal and increased platelet response to agonists, both in vitro and ex vivo in subjects exposed to PFAS. All the functional responses are increased in platelets by incorporation of PFAS: adhesion, aggregation, microvesicles release and experimental thrombus formation. These findings offer mechanistic support the hypothesis that platelet-centred mechanisms may be implicated in the increase in cardiovascular events observed in populations chronically exposed to PFAS.

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Figure 1 Updated hypothesis on the association of exposure to PFAS with cardiovascular disease and death. PFAS may promote arterial thrombosis by increasing cardiovascular risk (causing lipid and glucose disorders and arterial hypertension) or by directly activating platelets. (A) functional endothelial and resting circulating platelets; (B) exposure to PFAS and cardiovascular risk factors induce endothelial dysfunction and the activation of circulating platelets (release of microvesicles); (C) exposure to PFAS directly induces platelet adhesion and aggregation when endothelium has been removed or damaged and collagen is exposed to blood flow (release of prothrombotic substances and microvesicles from aggregating platelets) thus causing arterial thrombosis.CC BY · PubMed Central

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Additional file 45 of Characterizing PFAS hazards and risks: a human population-based in vitro cardiotoxicity assessment strategy
Ford, L. C., Lin, H.-C., Zhou, Y., Wright, F. A., Gombar, V. K., Sedykh, A., Shah, R., Chiu, W. A., & Rusyn, I. (2024) · Figshare · doi:10.6084/m9.figshare.26944878
Additional file 6 of Characterizing PFAS hazards and risks: a human population-based in vitro cardiotoxicity assessment strategy
Ford, L. C., Lin, H.-C., Zhou, Y., Wright, F. A., Gombar, V. K., Sedykh, A., Shah, R., Chiu, W. A., & Rusyn, I. (2024) · Figshare · doi:10.6084/m9.figshare.26944761
Additional file 34 of Characterizing PFAS hazards and risks: a human population-based in vitro cardiotoxicity assessment strategy
Ford, L. C., Lin, H.-C., Zhou, Y., Wright, F. A., Gombar, V. K., Sedykh, A., Shah, R., Chiu, W. A., & Rusyn, I. (2024) · Figshare · doi:10.6084/m9.figshare.26944845
Additional file 21 of Characterizing PFAS hazards and risks: a human population-based in vitro cardiotoxicity assessment strategy
Ford, L. C., Lin, H.-C., Zhou, Y., Wright, F. A., Gombar, V. K., Sedykh, A., Shah, R., Chiu, W. A., & Rusyn, I. (2024) · Figshare · doi:10.6084/m9.figshare.26944806
Additional file 31 of Characterizing PFAS hazards and risks: a human population-based in vitro cardiotoxicity assessment strategy
Ford, L. C., Lin, H.-C., Zhou, Y., Wright, F. A., Gombar, V. K., Sedykh, A., Shah, R., Chiu, W. A., & Rusyn, I. (2024) · Figshare · doi:10.6084/m9.figshare.26944836
Additional file 49 of Characterizing PFAS hazards and risks: a human population-based in vitro cardiotoxicity assessment strategy
Ford, L. C., Lin, H.-C., Zhou, Y., Wright, F. A., Gombar, V. K., Sedykh, A., Shah, R., Chiu, W. A., & Rusyn, I. (2024) · Figshare · doi:10.6084/m9.figshare.26944890
Additional file 3 of Characterizing PFAS hazards and risks: a human population-based in vitro cardiotoxicity assessment strategy
Ford, L. C., Lin, H.-C., Zhou, Y., Wright, F. A., Gombar, V. K., Sedykh, A., Shah, R., Chiu, W. A., & Rusyn, I. (2024) · Figshare · doi:10.6084/m9.figshare.26944752
Additional file 12 of Characterizing PFAS hazards and risks: a human population-based in vitro cardiotoxicity assessment strategy
Ford, L. C., Lin, H.-C., Zhou, Y., Wright, F. A., Gombar, V. K., Sedykh, A., Shah, R., Chiu, W. A., & Rusyn, I. (2024) · Figshare · doi:10.6084/m9.figshare.26944779
Additional file 4 of Characterizing PFAS hazards and risks: a human population-based in vitro cardiotoxicity assessment strategy
Ford, L. C., Lin, H.-C., Zhou, Y., Wright, F. A., Gombar, V. K., Sedykh, A., Shah, R., Chiu, W. A., & Rusyn, I. (2024) · Figshare · doi:10.6084/m9.figshare.26944755
Additional file 32 of Characterizing PFAS hazards and risks: a human population-based in vitro cardiotoxicity assessment strategy
Ford, L. C., Lin, H.-C., Zhou, Y., Wright, F. A., Gombar, V. K., Sedykh, A., Shah, R., Chiu, W. A., & Rusyn, I. (2024) · Figshare · doi:10.6084/m9.figshare.26944839
Additional file 7 of Characterizing PFAS hazards and risks: a human population-based in vitro cardiotoxicity assessment strategy
Ford, L. C., Lin, H.-C., Zhou, Y., Wright, F. A., Gombar, V. K., Sedykh, A., Shah, R., Chiu, W. A., & Rusyn, I. (2024) · Figshare · doi:10.6084/m9.figshare.26944764
Additional file 41 of Characterizing PFAS hazards and risks: a human population-based in vitro cardiotoxicity assessment strategy
Ford, L. C., Lin, H.-C., Zhou, Y., Wright, F. A., Gombar, V. K., Sedykh, A., Shah, R., Chiu, W. A., & Rusyn, I. (2024) · Figshare · doi:10.6084/m9.figshare.26944866
Additional file 20 of Characterizing PFAS hazards and risks: a human population-based in vitro cardiotoxicity assessment strategy
Ford, L. C., Lin, H.-C., Zhou, Y., Wright, F. A., Gombar, V. K., Sedykh, A., Shah, R., Chiu, W. A., & Rusyn, I. (2024) · Figshare · doi:10.6084/m9.figshare.26944803
Additional file 28 of Characterizing PFAS hazards and risks: a human population-based in vitro cardiotoxicity assessment strategy
Ford, L. C., Lin, H.-C., Zhou, Y., Wright, F. A., Gombar, V. K., Sedykh, A., Shah, R., Chiu, W. A., & Rusyn, I. (2024) · Figshare · doi:10.6084/m9.figshare.26944827
Additional file 23 of Characterizing PFAS hazards and risks: a human population-based in vitro cardiotoxicity assessment strategy
Ford, L. C., Lin, H.-C., Zhou, Y., Wright, F. A., Gombar, V. K., Sedykh, A., Shah, R., Chiu, W. A., & Rusyn, I. (2024) · Figshare · doi:10.6084/m9.figshare.26944812
Additional file 40 of Characterizing PFAS hazards and risks: a human population-based in vitro cardiotoxicity assessment strategy
Ford, L. C., Lin, H.-C., Zhou, Y., Wright, F. A., Gombar, V. K., Sedykh, A., Shah, R., Chiu, W. A., & Rusyn, I. (2024) · Figshare · doi:10.6084/m9.figshare.26944863
Additional file 9 of Characterizing PFAS hazards and risks: a human population-based in vitro cardiotoxicity assessment strategy
Ford, L. C., Lin, H.-C., Zhou, Y., Wright, F. A., Gombar, V. K., Sedykh, A., Shah, R., Chiu, W. A., & Rusyn, I. (2024) · Figshare · doi:10.6084/m9.figshare.26944770
Additional file 2 of Characterizing PFAS hazards and risks: a human population-based in vitro cardiotoxicity assessment strategy
Ford, L. C., Lin, H.-C., Zhou, Y., Wright, F. A., Gombar, V. K., Sedykh, A., Shah, R., Chiu, W. A., & Rusyn, I. (2024) · Figshare · doi:10.6084/m9.figshare.26944749
Additional file 26 of Characterizing PFAS hazards and risks: a human population-based in vitro cardiotoxicity assessment strategy
Ford, L. C., Lin, H.-C., Zhou, Y., Wright, F. A., Gombar, V. K., Sedykh, A., Shah, R., Chiu, W. A., & Rusyn, I. (2024) · Figshare · doi:10.6084/m9.figshare.26944821
Additional file 44 of Characterizing PFAS hazards and risks: a human population-based in vitro cardiotoxicity assessment strategy
Ford, L. C., Lin, H.-C., Zhou, Y., Wright, F. A., Gombar, V. K., Sedykh, A., Shah, R., Chiu, W. A., & Rusyn, I. (2024) · Figshare · doi:10.6084/m9.figshare.26944875
Additional file 47 of Characterizing PFAS hazards and risks: a human population-based in vitro cardiotoxicity assessment strategy
Ford, L. C., Lin, H.-C., Zhou, Y., Wright, F. A., Gombar, V. K., Sedykh, A., Shah, R., Chiu, W. A., & Rusyn, I. (2024) · Figshare · doi:10.6084/m9.figshare.26944884
Additional file 42 of Characterizing PFAS hazards and risks: a human population-based in vitro cardiotoxicity assessment strategy
Ford, L. C., Lin, H.-C., Zhou, Y., Wright, F. A., Gombar, V. K., Sedykh, A., Shah, R., Chiu, W. A., & Rusyn, I. (2024) · Figshare · doi:10.6084/m9.figshare.26944869
Additional file 37 of Characterizing PFAS hazards and risks: a human population-based in vitro cardiotoxicity assessment strategy
Ford, L. C., Lin, H.-C., Zhou, Y., Wright, F. A., Gombar, V. K., Sedykh, A., Shah, R., Chiu, W. A., & Rusyn, I. (2024) · Figshare · doi:10.6084/m9.figshare.26944854
Additional file 29 of Characterizing PFAS hazards and risks: a human population-based in vitro cardiotoxicity assessment strategy
Ford, L. C., Lin, H.-C., Zhou, Y., Wright, F. A., Gombar, V. K., Sedykh, A., Shah, R., Chiu, W. A., & Rusyn, I. (2024) · Figshare · doi:10.6084/m9.figshare.26944830
Additional file 1 of Characterizing PFAS hazards and risks: a human population-based in vitro cardiotoxicity assessment strategy
Ford, L. C., Lin, H.-C., Zhou, Y., Wright, F. A., Gombar, V. K., Sedykh, A., Shah, R., Chiu, W. A., & Rusyn, I. (2024) · Figshare · doi:10.6084/m9.figshare.26944746
Additional file 43 of Characterizing PFAS hazards and risks: a human population-based in vitro cardiotoxicity assessment strategy
Ford, L. C., Lin, H.-C., Zhou, Y., Wright, F. A., Gombar, V. K., Sedykh, A., Shah, R., Chiu, W. A., & Rusyn, I. (2024) · Figshare · doi:10.6084/m9.figshare.26944872
Additional file 27 of Characterizing PFAS hazards and risks: a human population-based in vitro cardiotoxicity assessment strategy
Ford, L. C., Lin, H.-C., Zhou, Y., Wright, F. A., Gombar, V. K., Sedykh, A., Shah, R., Chiu, W. A., & Rusyn, I. (2024) · Figshare · doi:10.6084/m9.figshare.26944824
Additional file 30 of Characterizing PFAS hazards and risks: a human population-based in vitro cardiotoxicity assessment strategy
Ford, L. C., Lin, H.-C., Zhou, Y., Wright, F. A., Gombar, V. K., Sedykh, A., Shah, R., Chiu, W. A., & Rusyn, I. (2024) · Figshare · doi:10.6084/m9.figshare.26944833
Additional file 1 of Association of per- and polyfluoroalkyl substances (PFAS) with periodontitis: the mediating role of sex hormones
Wu, Y., Qiu, Y., Wu, Y., Li, H., Yang, H., Deng, Q., He, B., Yan, F., Li, Y., & Chen, F. (2024) · Figshare · doi:10.6084/m9.figshare.25231249
Additional file 39 of Characterizing PFAS hazards and risks: a human population-based in vitro cardiotoxicity assessment strategy
Ford, L. C., Lin, H.-C., Zhou, Y., Wright, F. A., Gombar, V. K., Sedykh, A., Shah, R., Chiu, W. A., & Rusyn, I. (2024) · Figshare · doi:10.6084/m9.figshare.26944860
Additional file 8 of Characterizing PFAS hazards and risks: a human population-based in vitro cardiotoxicity assessment strategy
Ford, L. C., Lin, H.-C., Zhou, Y., Wright, F. A., Gombar, V. K., Sedykh, A., Shah, R., Chiu, W. A., & Rusyn, I. (2024) · Figshare · doi:10.6084/m9.figshare.26944767
Additional file 25 of Characterizing PFAS hazards and risks: a human population-based in vitro cardiotoxicity assessment strategy
Ford, L. C., Lin, H.-C., Zhou, Y., Wright, F. A., Gombar, V. K., Sedykh, A., Shah, R., Chiu, W. A., & Rusyn, I. (2024) · Figshare · doi:10.6084/m9.figshare.26944818
Additional file 11 of Characterizing PFAS hazards and risks: a human population-based in vitro cardiotoxicity assessment strategy
Ford, L. C., Lin, H.-C., Zhou, Y., Wright, F. A., Gombar, V. K., Sedykh, A., Shah, R., Chiu, W. A., & Rusyn, I. (2024) · Figshare · doi:10.6084/m9.figshare.26944776
Additional file 14 of Characterizing PFAS hazards and risks: a human population-based in vitro cardiotoxicity assessment strategy
Ford, L. C., Lin, H.-C., Zhou, Y., Wright, F. A., Gombar, V. K., Sedykh, A., Shah, R., Chiu, W. A., & Rusyn, I. (2024) · Figshare · doi:10.6084/m9.figshare.26944785
Additional file 48 of Characterizing PFAS hazards and risks: a human population-based in vitro cardiotoxicity assessment strategy
Ford, L. C., Lin, H.-C., Zhou, Y., Wright, F. A., Gombar, V. K., Sedykh, A., Shah, R., Chiu, W. A., & Rusyn, I. (2024) · Figshare · doi:10.6084/m9.figshare.26944887
Additional file 17 of Characterizing PFAS hazards and risks: a human population-based in vitro cardiotoxicity assessment strategy
Ford, L. C., Lin, H.-C., Zhou, Y., Wright, F. A., Gombar, V. K., Sedykh, A., Shah, R., Chiu, W. A., & Rusyn, I. (2024) · Figshare · doi:10.6084/m9.figshare.26944794
Additional file 15 of Characterizing PFAS hazards and risks: a human population-based in vitro cardiotoxicity assessment strategy
Ford, L. C., Lin, H.-C., Zhou, Y., Wright, F. A., Gombar, V. K., Sedykh, A., Shah, R., Chiu, W. A., & Rusyn, I. (2024) · Figshare · doi:10.6084/m9.figshare.26944788
Additional file 24 of Characterizing PFAS hazards and risks: a human population-based in vitro cardiotoxicity assessment strategy
Ford, L. C., Lin, H.-C., Zhou, Y., Wright, F. A., Gombar, V. K., Sedykh, A., Shah, R., Chiu, W. A., & Rusyn, I. (2024) · Figshare · doi:10.6084/m9.figshare.26944815
Additional file 33 of Characterizing PFAS hazards and risks: a human population-based in vitro cardiotoxicity assessment strategy
Ford, L. C., Lin, H.-C., Zhou, Y., Wright, F. A., Gombar, V. K., Sedykh, A., Shah, R., Chiu, W. A., & Rusyn, I. (2024) · Figshare · doi:10.6084/m9.figshare.26944842
Additional file 16 of Characterizing PFAS hazards and risks: a human population-based in vitro cardiotoxicity assessment strategy
Ford, L. C., Lin, H.-C., Zhou, Y., Wright, F. A., Gombar, V. K., Sedykh, A., Shah, R., Chiu, W. A., & Rusyn, I. (2024) · Figshare · doi:10.6084/m9.figshare.26944791
Additional file 18 of Characterizing PFAS hazards and risks: a human population-based in vitro cardiotoxicity assessment strategy
Ford, L. C., Lin, H.-C., Zhou, Y., Wright, F. A., Gombar, V. K., Sedykh, A., Shah, R., Chiu, W. A., & Rusyn, I. (2024) · Figshare · doi:10.6084/m9.figshare.26944797
Additional file 13 of Characterizing PFAS hazards and risks: a human population-based in vitro cardiotoxicity assessment strategy
Ford, L. C., Lin, H.-C., Zhou, Y., Wright, F. A., Gombar, V. K., Sedykh, A., Shah, R., Chiu, W. A., & Rusyn, I. (2024) · Figshare · doi:10.6084/m9.figshare.26944782
Additional file 10 of Characterizing PFAS hazards and risks: a human population-based in vitro cardiotoxicity assessment strategy
Ford, L. C., Lin, H.-C., Zhou, Y., Wright, F. A., Gombar, V. K., Sedykh, A., Shah, R., Chiu, W. A., & Rusyn, I. (2024) · Figshare · doi:10.6084/m9.figshare.26944773
Additional file 36 of Characterizing PFAS hazards and risks: a human population-based in vitro cardiotoxicity assessment strategy
Ford, L. C., Lin, H.-C., Zhou, Y., Wright, F. A., Gombar, V. K., Sedykh, A., Shah, R., Chiu, W. A., & Rusyn, I. (2024) · Figshare · doi:10.6084/m9.figshare.26944851
Additional file 38 of Characterizing PFAS hazards and risks: a human population-based in vitro cardiotoxicity assessment strategy
Ford, L. C., Lin, H.-C., Zhou, Y., Wright, F. A., Gombar, V. K., Sedykh, A., Shah, R., Chiu, W. A., & Rusyn, I. (2024) · Figshare · doi:10.6084/m9.figshare.26944857
Additional file 35 of Characterizing PFAS hazards and risks: a human population-based in vitro cardiotoxicity assessment strategy
Ford, L. C., Lin, H.-C., Zhou, Y., Wright, F. A., Gombar, V. K., Sedykh, A., Shah, R., Chiu, W. A., & Rusyn, I. (2024) · Figshare · doi:10.6084/m9.figshare.26944848
Additional file 22 of Characterizing PFAS hazards and risks: a human population-based in vitro cardiotoxicity assessment strategy
Ford, L. C., Lin, H.-C., Zhou, Y., Wright, F. A., Gombar, V. K., Sedykh, A., Shah, R., Chiu, W. A., & Rusyn, I. (2024) · Figshare · doi:10.6084/m9.figshare.26944809
Additional file 5 of Characterizing PFAS hazards and risks: a human population-based in vitro cardiotoxicity assessment strategy
Ford, L. C., Lin, H.-C., Zhou, Y., Wright, F. A., Gombar, V. K., Sedykh, A., Shah, R., Chiu, W. A., & Rusyn, I. (2024) · Figshare · doi:10.6084/m9.figshare.26944758
Additional file 19 of Characterizing PFAS hazards and risks: a human population-based in vitro cardiotoxicity assessment strategy
Ford, L. C., Lin, H.-C., Zhou, Y., Wright, F. A., Gombar, V. K., Sedykh, A., Shah, R., Chiu, W. A., & Rusyn, I. (2024) · Figshare · doi:10.6084/m9.figshare.26944800
Additional file 46 of Characterizing PFAS hazards and risks: a human population-based in vitro cardiotoxicity assessment strategy
Ford, L. C., Lin, H.-C., Zhou, Y., Wright, F. A., Gombar, V. K., Sedykh, A., Shah, R., Chiu, W. A., & Rusyn, I. (2024) · Figshare · doi:10.6084/m9.figshare.26944881
Tracing PFAS from the environment to the food chain: Human health impacts, in vivo toxicological insights, and detection approaches
Dimri, S., Bisht, B., Vlaskin, M., Kurbatova, A., Jaiswal, K. K., Rajput, V. S., Sharma, R., Chauhan, P. K., & Kumar, V. (2025) · Food and Humanity · doi:10.1016/j.foohum.2025.100982
Systematic review on internal exposure to per- and polyfluoroalkyl substances (PFAS) and risk of ischemic heart diseases
Bauer, M. L., Weikert, C., Knüppel, S., Monien, B. H., Abraham, K., & Menzel, J. (2026) · Environment International · doi:10.1016/j.envint.2026.110278
Acute exposure to perfluorooctanoic acid during cardiomyogenesis disrupts transcriptional and electrophysiological profiles in differentiated myocytes
Ishikawa, T., Clark, C. W., Tapaswi, A., Sala-Hamrick, K. E., Herron, T. J., Jiménez‐Vázquez, E. N., Jain, A., Jones, D. K., Colacino, J. A., da Rocha, A. M., et al. (2026) · Toxicological Sciences · doi:10.1093/toxsci/kfag107 · Cited by 1

Authors: Meneguzzi, A., Fava, C., Castelli, M., & Minuz, P.
Affiliations: University of Verona (IT)
Corresponding author: Minuz, Pietro
ORCID: Meneguzzi, Alessandra
Fava, Cristiano
Castelli, Marco
Minuz, Pietro
Venue: Frontiers in Endocrinology
Publisher: Frontiers Media SA
Published: 2021-07-09
Volume: 12
Pages: 706352-706352
ISSN: 1664-2392 (ISSN-L)
DOI: 10.3389/fendo.2021.706352
PMC: PMC8298860
OpenAlex: W3179412230
Cited by: 174
References: 83
Citations by year: 2026: 23 · 2025: 43 · 2024: 58 · 2023: 31 · 2022: 19
FWCI: 2.67
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (vor)
Locations: Frontiers in Endocrinology (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics: Physical Sciences › Environmental Science › Environmental Chemistry › Per- and polyfluoroalkyl substances research
Physical Sciences › Chemistry › Organic Chemistry › Fluorine in Organic Chemistry
Physical Sciences › Materials Science › Polymers and Plastics › Synthesis and properties of polymers
Keywords: perfluorinated compounds, PFAS exposure, cardiovascular disease, thromboembolism, platelets, atherosclerosis, glycolipid metabolism, blood pressure, thrombus formation, platelet microparticles, plasma membrane fluidity, calcium signaling, environmental pollution
MeSH terms: Blood Platelets, Cardiovascular Diseases, Environmental Pollutants, Fluorocarbons, Humans, Thrombosis

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Exposure to Perfluoroalkyl Chemicals and Cardiovascular Disease: Experimental and Epidemiological Evidence

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