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Factor XII activation is essential to sustain the procoagulant effects of particulate matter
- Kilinç, E (author)
- Van Oerle, R (author)
- Borissoff, J I (author)
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- Oschatz, C (author)
- Gerlofs-Nijland, M E (author)
- Janssen, N A (author)
- Cassee, F R (author)
- Ten Cate, H (author)
- Spronk, H M H (author)
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- (creator_code:org_t)
- Elsevier BV, 2011
- 2011
- English.
- In: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 9:7, s. 1359-1367
- Journal article (peer-reviewed)
Abstract
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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 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.
Keyword
- air pollution
- blood coagulation
- factor XII
- intrinsic coagulation pathway
- particulate matter
- thrombin generation
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- ref (subject category)
- art (subject category)
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- Kilinç, E
- Van Oerle, R
- Borissoff, J I
- Oschatz, C
- Gerlofs-Nijland, ...
- Janssen, N A
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- Cassee, F R
- Sandström, Thoma ...
- Renné, T
- Ten Cate, H
- Spronk, H M H
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