Ultrafine Particles Affect Experimental Thrombosis in an In Vivo Hamster Model

Abstract

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 microg/kg body weight but not at 50 microg/kg body weight. In contrast, amine-polystyrene particles significantly enhanced thrombosis at 500 and 50 microg/kg body weight but not at 5 microg/kg body weight. Similarly, the intratracheal instillation of 5,000 microg 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 microM ADP, unmodified particles had no effect up to 100 microg/ml, and carboxylate-polystyrene particles weakly enhanced platelet aggregation at 25 to 100 microg/ml. However, amine-polystyrene particles (50 and 100 microg/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.

Ultrafine Particles Exert Prothrombotic but Not Inflammatory Effects on the Hepatic Microcirculation in Healthy Mice In Vivo

“…21,22,26 After hepatic ischemiareperfusion, in contrast to UFP exposure, platelet rolling precedes permanent adhesion, and platelet adhesion is not restricted to venules and sinusoids but rather is also observed in terminal arterioles. 20 Although UFPs were recently shown to enhance ADPinduced platelet activation, 14 we addressed the issue of whether platelet recruitment can be mediated by prothrombotic changes on the hepatic endothelium in response to the systemic infusion of particles. For this purpose, the intravascular distribution of fibrin(ogen) was determined in vivo using Alexa 488 -conjugated fibrinogen.…”

“…Indeed, Nemmar et al [12][13][14][15] have reported that intratracheally instilled UFPs are quickly translocated into the circulation and able to activate circulating platelets and affect experimental thrombosis. Because inflammatory and prothrombotic events manifest themselves on the level of the microcirculation, it is likely that the microvasculature represents the primary target for circulating particles or particles accumulated in extrapulmonary organs.…”

Air pollution and cardiac remodeling: a role for RhoA/Rho-kinase

“…The locus of these interactions at the present time is unclear but there is intriguing information that inhaled particulates particularly those in the ultrafine range, may directly transgress into the circulation where it may mediate effects. (33,34,45) There is also interesting evidence of heightened oxidant stress with inhaled particulates in the myocardium mediated through the autonomic nervous system. (15) Regardless of the mechanism, the fact that inhaled particles induce these effects in the myocardium in hypertension has important implications for the cardiovascular effects of air pollution.…”

Translocation Pathway of the Intratracheally Instilled Ultrafine Particles from the Lung into the Blood Circulation in the Mouse

“…In addition, morphological study showed instilled 30 nm gold particles in capillaries within 30 minutes' postexposure (Berry et al, 1977) and inhaled ultrafine titanium dioxide particles at alveolar wall and in capillaries at 1 hour after the end of exposure (Geiser et al, 2005). UFPs in the blood circulation can directly or indirectly influence hemostasis or cardiovascular integrity and thus induce adverse cardiovascular endpoints more directly (Nemmar et al, 2002b(Nemmar et al, , 2003a(Nemmar et al, , 2003b. The exact pathway for this translocation, however, remains unclear.…”