Increased Cardiovascular Risk Associated with Chemical Sensitivity to Perfluoro-Octanoic Acid: Role of Impaired Platelet Aggregation.

Luca De Toni,Claudia Maria Radu,Carlo Foresta,Diego Guidolin,Iva Sabovic,Elena Campello,Andrea Di Nisio,Paolo Simioni,Stefano Dall’Acqua,Salvatore Spampinato

doi:10.3390/ijms21020399

Abstract

Perfluoro–alkyl substances (PFAS), particularly perfluoro–octanoic acid (PFOA), are persisting environmental chemicals showing bioaccumulation in human tissues. Recently, exposure to PFAS has been associated with increased prevalence of cardiovascular diseases (CVDs). However, a causal role of PFAS in atherosclerosis pathogenesis is under-investigated. Here, we investigated the effect of PFOA exposure on platelets’ function, a key player in atherosclerosis process. PFOA accumulation in platelets was evaluated by liquid chromatography-mass spectrometry. Changes in platelets’ membrane fluidity and activation after dose-dependent exposure to PFOA were evaluated by merocyanine 540 (MC540) and anti P-Selectin immune staining at flow cytometry, respectively. Intracellular calcium trafficking was analyzed with Fluo4M probe, time-lapse live imaging. Platelets’ aggregation state was also evaluated with Multiplate® aggregometry analyzer in 48 male subjects living in a specific area of the Veneto region with high PFAS environmental pollution, and compared with 30 low-exposure control subjects. Platelets’ membrane was the major target of PFOA, whose dose-dependent accumulation was associated in turn with increased membrane fluidity, as expected by a computational model; increased activation at resting condition; and both calcium uptake and aggregation upon activation. Finally, exposed subjects had higher serum and platelets levels of PFOA, together with increased aggregation parameters at Multiplate®, compared with controls. These data help to explain the emerging association between PFAS exposure and CVD.

Highlights

Perfluoro–alkyl substances (PFAS), such as perfluoro–octanoic acid (PFOA) and perfluoro–octane–sulfonate (PFOS), are a class of organic molecules characterized by the high degree of fluorination of hydrocarbon chains, and are extensively used in industry and consumer products, including oil and water repellents, coatings for cookware, carpets, and textiles
Properties like grease repellency and flame retardation have led to a widespread use of PFAS in industrial and consumer products since the introduction of the compounds, and they can be found in a variety of consumer goods
PFAS can be absorbed by the intestine or inhaled and, once in the circulation, they may act as endocrine disruptors (ED), leading to severe health consequences, such as neonatal mortality, neurotoxicity, immunotoxicity, and reproductive disorders [3,4]

Summary

Introduction

Perfluoro–alkyl substances (PFAS), such as perfluoro–octanoic acid (PFOA) and perfluoro–octane–sulfonate (PFOS), are a class of organic molecules characterized by the high degree of fluorination of hydrocarbon chains, and are extensively used in industry and consumer products, including oil and water repellents, coatings for cookware, carpets, and textiles. The elimination of PFAS from the serum of a highly exposed human subjects was estimated to be approximately 5 to 8.5 years, whereas in murine models, it is much shorter [5]. On these bases, in 2015, PFOA was classified as a possible carcinogenic agent (2B group) to humans by the International Agency for Research on Cancer (IARC) [6]

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