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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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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