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

Int J Mol Sci. 2020 Jan 8;21(2):399. doi: 10.3390/ijms21020399.


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.

Keywords: cardiovascular diseases; liquid chromatography-mass spectrometry, membrane fluidity, platelets’ aggregation; perfluoro–alkyl substances.

MeSH terms

  • Adult
  • Blood Platelets / drug effects*
  • Caprylates / toxicity
  • Cardiovascular Diseases / blood*
  • Cardiovascular Diseases / chemically induced
  • Cardiovascular Diseases / pathology
  • Environmental Pollution / analysis
  • Fluorocarbons / toxicity*
  • Humans
  • Italy
  • Male
  • Platelet Aggregation / drug effects
  • Platelet Function Tests
  • Risk Factors
  • Water Pollutants, Chemical / toxicity*
  • Young Adult


  • Caprylates
  • Fluorocarbons
  • Water Pollutants, Chemical
  • perfluorooctane
  • octanoic acid