Abstract | BACKGROUND: Accelerated thrombus formation induced by exposure to combustion-derived air pollution has been linked to alterations in endogenous fibrinolysis and platelet activation in response to pulmonary and systemic inflammation. We hypothesised that mechanisms independent of inflammation contribute to accelerated thrombus formation following exposure to diesel exhaust particles ( DEP). METHODS: RESULTS: Instillation of DEP reduced the time to thrombotic occlusion in vivo, coinciding with the peak of DEP-induced pulmonary inflammation (6 h). CB and DQ12 produced greater inflammation than DEP but did not alter time to thrombotic occlusion. Intravenous DEP produced an earlier (2 h) acceleration of thrombosis (as did CB) without pulmonary or systemic inflammation. DEP inhibited t-PA and PAI-1 release from HUVECs, and reduced the t-PA/PAI-1 ratio in vivo; similar effects in vivo were seen with CB and DQ12. DEP, but not CB or DQ12, increased platelet-monocyte aggregates. CONCLUSION:
DEP accelerates arterial thrombus formation through increased platelet activation. This effect is dissociated from pulmonary and systemic inflammation and from impaired fibrinolytic function.
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Authors | Caroline M Tabor, Catherine A Shaw, Sarah Robertson, Mark R Miller, Rodger Duffin, Ken Donaldson, David E Newby, Patrick W F Hadoke |
Journal | Particle and fibre toxicology
(Part Fibre Toxicol)
Vol. 13
Pg. 6
(Feb 09 2016)
ISSN: 1743-8977 [Electronic] England |
PMID | 26857113
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Inflammation Mediators
- Plasminogen Activator Inhibitor 1
- SERPINE1 protein, human
- Soot
- Vehicle Emissions
- Quartz
- Tissue Plasminogen Activator
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Topics |
- Animals
- Arterial Occlusive Diseases
(blood, chemically induced)
- Blood Platelets
(drug effects, metabolism)
- Bronchoalveolar Lavage Fluid
(chemistry)
- Carotid Stenosis
(blood, chemically induced)
- Cells, Cultured
- Fibrinolysis
(drug effects)
- Human Umbilical Vein Endothelial Cells
(drug effects, metabolism)
- Inflammation Mediators
(blood)
- Male
- Particle Size
- Plasminogen Activator Inhibitor 1
(metabolism)
- Platelet Activation
- Platelet Adhesiveness
(drug effects)
- Pneumonia
(blood, chemically induced)
- Quartz
(toxicity)
- Rats, Wistar
- Soot
(toxicity)
- Thrombosis
(blood, chemically induced)
- Time Factors
- Tissue Plasminogen Activator
(metabolism)
- Vehicle Emissions
(toxicity)
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