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Ultrafine Particles Affect Experimental Thrombosis in an In Vivo Hamster Model

Laboratory of Pneumology, Unit of Lung Toxicology; and Center for Molecular and Vascular Biology, K.U. Leuven, Leuven, Belgium; and MRC Toxicology Unit, Leicester, United Kingdom

Correspondence and requests for reprints should be addressed to Prof. B. Nemery, Laboratory of Pneumology, Unit of Lung Toxicology, K.U. Leuven, Herestraat 49, B-3000 Leuven, Belgium. E-mail: ben.nemery{at}med.kuleuven.ac.be

Particulate air pollution is associated with cardiovascular morbidity and mortality. To investigate this association, we studied the effect of ultrafine (60 nm) polystyrene particles on thrombus formation in a hamster model after intravenous and intratracheal administration of unmodified, carboxylate-polystyrene, or amine-polystyrene particles. Unmodified particles had no effect on thrombosis up to 5 mg/kg. Carboxylate-polystyrene particles significantly inhibited thrombus formation at 500 and 100 µg/kg body weight but not at 50 µg/kg body weight. In contrast, amine-polystyrene particles significantly enhanced thrombosis at 500 and 50 µg/kg body weight but not at 5 µg/kg body weight. Similarly, the intratracheal instillation of 5,000 µg of amine-polystyrene particles significantly increased thrombus formation. The unmodified particles and carboxylate-polystyrene particles had no effect. During platelet aggregation in human platelet-rich plasma, induced with 1.25 µM ADP, unmodified particles had no effect up to 100 µg/ml, and carboxylate-polystyrene particles weakly enhanced platelet aggregation at 25 to 100 µg/ml. However, amine-polystyrene particles (50 and 100 µg/ml) induced platelet aggregation themselves and strongly increased the ADP-induced aggregation. We conclude that the presence of (ultrafine) particles in the circulation may affect hemostasis. The observed in vivo prothrombotic tendency results, at least in part, from platelet activation by positively charged amine-polystyrene particles.

Key Words: air pollution • cardiovascular effects • hemostasis • platelets • ultrafine particles

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