Tissue factor, fibrinolysis and the cardiovascular health effects of PM10
P. S. Gilmour, W. MacNee, K. Donaldson (Edinburgh, United Kingdom)
Source: Annual Congress 2002 - Effects of air pollution on lung cells
Session: Effects of air pollution on lung cells
Session type: Oral Presentation
Number: 261
Disease area: Airway diseases, Pulmonary vascular diseases
Abstract Cardiovascular-related (CV) adverse health effects are associated with environmental particles (PM10). These effects may be the result of PM10-enhanced thrombus formation in the vasculature. Increased expression of tissue factor (TF) leading to activation of the intrinsic coagulation pathway via Factor VII may form a mechanism for coagulation leading to CV effects. Fibrinolysis is mediated by tissue plasminogen activator (tPA), and inhibited by plasminogen activator inhibitor-1 (PAI-1). The balance between the endogenous release of these factors appears also to be a critical event in thrombus formation. We hypothesised that PM10 exposure causes TF expression and changes in fibrinolysis-related gene expression and protein in endothelial cells and macrophages. We studied the effects of PM10 and LPS on mRNA expression by RTPCR in human umbilical vascular endothelial cells (HUVEC) and human monocyte derived macrophages (HM). In HUVECs LPS and PM10 increased TF mRNA expression at 4 hours (4.6 and 4.2 fold increase vs control respectively; p<0.01) in a dose dependent manner. Expression of tPA in HUVECs was significantly decreased by PM10 and LPS treatment (6.5 and 1.9 fold decrease vs control p<0.01). PM10 significantly increased TF expression (2.7 fold vs control, p<0.05) in HMs with a complementary increase in PAI-1 expression (2.4 fold vs control, p<0.01). These data show that, in endothelial cells and HMs, PM10 increases the expression of the procoagulant gene TF and alters thrombolytic balance towards coagulation. These mechanisms may contribute to the cardiovascular effects of PM10. Colt Foundation, MRC UK, The British Lung Foundation
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P. S. Gilmour, W. MacNee, K. Donaldson (Edinburgh, United Kingdom). Tissue factor, fibrinolysis and the cardiovascular health effects of PM10. Eur Respir J 2002; 20: Suppl. 38, 261
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