Journal
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
Volume 9, Issue 7, Pages 1359-1367Publisher
WILEY
DOI: 10.1111/j.1538-7836.2011.04280.x
Keywords
air pollution; blood coagulation; factor XII; intrinsic coagulation pathway; particulate matter; thrombin generation
Categories
Funding
- Netherlands Heart Foundation [2006B064]
- VR [K2010-64X21462013]
- European Commission [MEST-CT-2005-020706]
- European Union [QLRT-1999-01582]
- RIVM strategic research program
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Background: Particulate matter (PM) is a key component of ambient air pollution and has been associated with an increased risk of thrombotic events and mortality. The underlying mechanisms remain unclear. Objectives: To study the mechanisms of PM-driven procoagulant activity in human plasma and to investigate mainly, the coagulation driven by ultrafine particles (UFPs; < 0.1 mu m) in genetically modified mice. Methods: Thrombin generation in response to PM of different sizes was assessed in normal human platelet-poor plasma, as well as in plasmas deficient in the intrinsic pathway proteases factors XII (FXII) or XI (FXI). In addition, UFPs were intratracheally instilled in wild-type (WT) and FXII-deficient (FXII-/-) mice and plasma thrombin generation was analyzed in plasma from treated mice at 4 and 20 h post-exposure. Results: In normal human plasma, thrombin generation was enhanced in the presence of PM, where as PM-driven thrombin formation was completely abolished in FXII-and FXI-deficient plasma. UFPs induced a transient increase in tissue factor (TF)-driven thrombin formation at 4 h post-instillation in WT mice compared with saline instillation. Intratracheal instillation of UFPs resulted in a procoagulant response in WT mice plasma at 20 h, whereas it was entirely suppressed in FXII-/- mice. Conclusions: Overall, the data suggest that PM promotes its early procoagulant actions mostly through the TF-driven extrinsic pathway of coagulation, whereas PM-driven long lasting thrombogenic effects are predominantly mediated via formation of activated FXII. Hence, FXII-driven thrombin formation may be relevant to an enhanced thrombotic susceptibility upon chronic exposure to PM in humans.
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