Factor XII activation is essential to sustain the procoagulant effects of particulate matter
2011 (English)In: Journal of Thrombosis and Haemostasis, ISSN 1538-7933, E-ISSN 1538-7836, Vol. 9, no 7, 1359-1367 p.Article in journal (Refereed) Published
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 μm) 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, whereas 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.
Place, publisher, year, edition, pages
2011. Vol. 9, no 7, 1359-1367 p.
air pollution, blood coagulation, factor XII, intrinsic coagulation pathway, particulate matter, thrombin generation
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:umu:diva-51285DOI: 10.1111/j.1538-7836.2011.04280.xPubMedID: 21481175OAI: oai:DiVA.org:umu-51285DiVA: diva2:478538