Alteration of fibrin clot properties by ultrafine particulate matter.
Both long- and short-term (1-2 hours) exposure to particulate matter (PM) are associated with morbidity and mortality caused by cardiovascular diseases. One of the underlying mechanisms may be due to changes to blood coagulability upon exposure to PM. We investigated this possibility by measuring differences in blood clots formed in the presence of particulate matter in vitro. Total (T)PM increased the permeation of clots in a dose-dependant manner. Filtered (F)PM (17 microg/ml) also produced a significant increase in permeation. Turbidity measured as maximum optical density (ODmax) was increased in a dose-dependant manner with increasing concentration of TPM and FPM. Turbidity measurements also showed a significantly faster rate of polymerisation in the presence of 68 microg/ml FPM. Laser scanning confocal microscopy (LSCM) showed a decrease in fibre density without a significant increase in fibre diameter. However, LSCM showed increased clot heterogeneity due to fibre clustering, creating areas of denser fibrin network surrounded by looser network. The presence of reactive oxygen species (ROS) scavenger mannitol inhibited the effects on fibre clustering. Our data show that TPM and FPM cause alterations in fibrin clot structure, likely through the formation of ROS. These changes in fibrin clot structure may play a role in thromboembolic events upon PM exposure.
Metassan
Sofian
S
Molecular Epidemiology Unit, Leeds Institute for Health, Genetics and Therapeutics, Faculty of Medicine and Health, University of Leeds, UK.
Charlton
Alexander J
AJ
Routledge
Michael N
MN
Scott
D Julian A
DJ
Ariëns
Robert A S
RA
D001777:Blood Coagulation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005337:Fibrin / Q000378:metabolism* / Q000648:ultrastructure; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008353:Mannitol / Q000494:pharmacology; D018613:Microscopy, Confocal; D009391:Nephelometry and Turbidimetry; D010316:Particle Size; D052638:Particulate Matter / Q000633:toxicity*; D016062:Porosity; D055503:Protein Multimerization; D017382:Reactive Oxygen Species / Q000378:metabolism; D013927:Thrombosis / Q000097:blood / Q000139:chemically induced*; D001335:Vehicle Emissions / Q000633:toxicity*
D016166:Free Radical Scavengers; D052638:Particulate Matter; D017382:Reactive Oxygen Species; D001335:Vehicle Emissions; D008353:Mannitol; D005337:Fibrin