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Title: Fibrin clot structure alterations after particulate matter exposure
Author: Pan, Xiaoxi
ISNI:       0000 0004 5990 0740
Awarding Body: University of Leeds
Current Institution: University of Leeds
Date of Award: 2016
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Particulate matter (PM) as an important part of ambient air pollution has been associated with increased risks of cardiovascular diseases. Fibrin clot structure alteration is an emerging risk factor of many cardiovascular diseases, especially thrombosis. Therefore, the aim of this study was to investigate whether and how air particulate matter affects fibrin clot structure and endothelial cell behaviour. Turbidity assay, turbidity lysis assay and laser scanning confocal microscopy were used to analyse clots formed from normal pooled plasma or purified fibrinogen, in the presence of varying concentrations of PM. It was found that clots formed from plasma with higher concentrations of particles led to prolonged lysis time compared to control. No differences were seen for clots formed from fibrinogen. In a study of clots formed from plasma samples collected as part of a previous study on the effects of air pollution on deep vein thrombosis (DVT), alterations were observed in clots formed from plasma of DVT patients exposed to high levels of PM compared to those exposed to low levels, but the same differences were not observed in clots formed from plasma of control subjects. To investigate the potential role of venous endothelial cells in moderating clot structure following exposure to PM, human umbilical vein endothelial cells (HUVEC) were treated with PM for 24 hours and clots subsequently formed on the cells. Clots formed from plasma on the treated cells were altered compared to controls. RT-PCR and ELISA results showed increased gene expression of tissue factor (TF), protein expression of von Willebrand Factor (VWF) and plasminogen activation inhibitor-1 (PAI-1) and decreased thrombomodulin mRNA expression which were consistent with changes observed in clot structure. Engineered SiO2 nanoparticles caused denser clot structure in clots formed from normal pooled plasma. The gene expression of thrombomodulin was inhibited by SiO2 nanoparticles, but there were no significant difference in the TF mRNA expression between control and treated cells. Silica NPs caused increased concentrations of VWF, but not PAI-1 produced by endothelial cells. The results presented here show that PM can induce changes to clot structure and function, and that changes in gene expression induced in endothelial cells may be a mechanism by which a prothrombotic state is induced in response to PM exposure. Furthermore, some, but not all, similar changes were observed in clots and cells exposed to SiO2 nanoparticles, raising the possibility that such engineered nanoparticles may also have the potential to contribute to cardiovascular toxicity.
Supervisor: Routledge, Michael ; Ariens, Robert ; Gong, Yun Yun Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available