Perfluoroalkyl and Polyfluoroalkyl Substances Interact with Platelet Glycoprotein Ibα and Exacerbate Thrombosis
Open accessAbstract
Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are highly stable man-made chemicals. They have recently garnered significant attention due to their ubiquitous presence in the environment and deleterious effects on human health including cardiovascular diseases (CVDs). Thrombosis due to platelet activation is a major aspect in CVDs. However, the direct effect and underlying mechanism of PFAS on the platelets remains elusive. Here, we observed that PFAS engagement with the extracellular domain of platelet GPIbα, transduced GPIbα-driven inward signals, resulting in intracellular calcium mobilization, activation of Akt and αⅡbβ3 integrin, culminating in platelet aggregation and procoagulant platelet formation. PFAS pretreatment enhanced GPIb-mediated platelet spreading and thrombus formation under high shear conditions. PFAS-induced platelet activation was markedly decreased in Gpibα-deficient mice. PFAS-primed platelets drove neutrophil extracellular traps formation through GPIbα-dependent pathway. Further, PFAS-exposed mice showed heightened risk of thrombus growth and ischemic stroke. Our findings provide experimental evidence for the causal links between PFAS exposure and thrombotic CVDs. Blockade of GPIbα and the downstream pathways could be an instrumental strategy against PFAS-induced platelet activation and thrombosis.
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PFAS engagement with platelet GPIbα triggers calcium influx, Akt activation, and αIIbβ3 integrin signaling, culminating in procoagulant platelet formation.
“Mechanistic studies reveal that PFAS engagement with platelet GPIbα triggers calcium influx, Akt activation, and αIIbβ3 integrin signaling, culminating in procoagulant platelet formation.”
From Exposure to Per- and Polyfluoroalkyl Substances (PFASs) in Healthcare: Environmental and Clinical Insights (2025) · cites this paper as [73]
Animal models exposed to PFASs show increased thrombus development and ischemic stroke.
“Animal models exposed to PFASs show increased thrombus development and ischemic stroke, suggesting potential targets (e.g., GPIbα) for mitigating PFAS-induced thrombosis [73].”
From Exposure to Per- and Polyfluoroalkyl Substances (PFASs) in Healthcare: Environmental and Clinical Insights (2025) · cites this paper as [73]
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Self-citationMICROPLÁSTICOS E SUBSTÂNCIAS PER- E POLIFLUOROALQUIL (PFAS): IMPLICAÇÕES CARDIOMETABÓLICAS
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Self-citation
- Authors
- Liu, M., Zhao, W., Ma, C., Awais, M., Chen, X., Feng, Y., Wang, T., Zhou, S., Bai, Y., Jiang, S., Zhang, D., Zhu, G., Xu, X. R., Xu, M., Ni, H., & Shen, C.
- Affiliations
- Ocean University of China (CN)
- St. Michael's Hospital (CA)
- Shandong University (CN)
- Corresponding author
- Ni, Heyu
- Shen, Chuanbin
- ORCID
- Venue
- Journal of Hazardous Materials
- Publisher
- Elsevier BV
- Published
- 2025-08
- Volume
- 494
- Pages
- 138506
- ISSN
- 0304-3894 (ISSN-L)
- OpenAlex
- W4410088724
- Cited by
- 12
- References
- 87
- Citations by year
- 2026: 7 · 2025: 5
- FWCI
- 8.87
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- Locations
- Journal of Hazardous Materials (publishedVersion)
- SSRN Electronic Journal (acceptedVersion)
- PubMed (publishedVersion)
- Funders
- Natural Science Foundation of Shandong Province (2024HWYQ-035)
- National Natural Science Foundation of China (32400941)
- Fundamental Research Funds for the Central Universities (842412013)
- Canadian Institutes of Health Research (389035)
- Topics
- Health Sciences › Medicine › Hematology › Platelet Disorders and Treatments
- Physical Sciences › Environmental Science › Environmental Chemistry › Per- and polyfluoroalkyl substances research
- Health Sciences › Medicine › Surgery › Heparin-Induced Thrombocytopenia and Thrombosis
- Keywords
- per- and polyfluoroalkyl substances, PFAS, platelet activation, GPIbα, thrombosis, platelet aggregation, calcium mobilization, Akt signaling, integrin αIIbβ3, neutrophil extracellular traps, ischemic stroke, thrombus formation, high shear
- MeSH terms
- Animals, Blood Platelets, Fluorocarbons, Humans, Male, Mice, Inbred C57BL, Platelet Aggregation, Thrombosis, Platelet Activation, Platelet Glycoprotein GPIb-IX Complex, Mice
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