Thrombogenic changes in young and old mice upon subchronic exposure to air pollution in an urban roadside tunnel

Jan Emmerechts; Vanessa De Vooght; Steven Haenen; Serena Loyen; Soetkin Van kerckhoven; Bianca Hemmeryckx; Jeroen A. J. Vanoirbeek; Peter H. Hoet; Ben Nemery; Marc F. Hoylaerts

doi:10.1160/TH12-03-0161

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2012; 108(04): 756-768
DOI: 10.1160/TH12-03-0161

Animal Models

Schattauer GmbH

Thrombogenic changes in young and old mice upon subchronic exposure to air pollution in an urban roadside tunnel

Authors

Jan Emmerechts

¹Center for Molecular and Vascular Biology, University of Leuven, Belgium
Vanessa De Vooght

²Occupational & Environmental Medicine, Unit of lung toxicology, University of Leuven, Belgium
Steven Haenen

²Occupational & Environmental Medicine, Unit of lung toxicology, University of Leuven, Belgium
Serena Loyen

¹Center for Molecular and Vascular Biology, University of Leuven, Belgium
Soetkin Van kerckhoven

¹Center for Molecular and Vascular Biology, University of Leuven, Belgium
Bianca Hemmeryckx

¹Center for Molecular and Vascular Biology, University of Leuven, Belgium
Jeroen A. J. Vanoirbeek

²Occupational & Environmental Medicine, Unit of lung toxicology, University of Leuven, Belgium
Peter H. Hoet

²Occupational & Environmental Medicine, Unit of lung toxicology, University of Leuven, Belgium
Ben Nemery

²Occupational & Environmental Medicine, Unit of lung toxicology, University of Leuven, Belgium
Marc F. Hoylaerts

¹Center for Molecular and Vascular Biology, University of Leuven, Belgium

Abstract

Summary

Epidemiological studies indicate that elderly persons are particularly susceptible to the cardiovascular health complications of air pollution, but pathophysiological mechanisms behind the increased susceptibility remain unclear. Therefore, we investigated how continuous traffic-related air pollution exposure affects haemostasis parameters in young and old mice. Young (10 weeks) and old (20 months) mice were placed in an urban roadside tunnel or in a clean environment for 25 or 26 days and markers of inflammation and endothelial cells or blood platelet activation were measured, respectively. Plasma microvesicles and pro/ anticoagulant factors were analysed, and thrombin generation analysis was performed. Despite elevated macrophage carbon load, tunnel mice showed no overt pulmonary or systemic inflammation, yet manifested reduced pulmonary thrombomudulin expression and elevated endothelial von Willebrand factor (VWF) expression in lung capillaries. In young mice, soluble P-selectin (sP-sel) increased with exposure and correlated with soluble E-selectin and VWF. Baseline plasma factor VIII (FVIII), sP-sel and VWF were higher in old mice, but did not pronouncedly increase further with exposure. Traffic-related air pollution markedly raised red blood cell and blood platelet numbers in young and old mice and procoagulant blood platelet-derived microvesicle numbers in old animals. Changes in coagulation factors and thrombin generation were mild or absent. Hence, continuous traffic-related air pollution did not trigger overt lung inflammation, yet modified pulmonary endothelial cell function and enhanced platelet activity. In old mice, subchronic exposure to polluted air raised platelet numbers, VWF, sP-sel and microvesicles to the highest values presently recorded, collectively substantiating a further elevation of thrombogenicity, already high at old age.

Keywords

Air pollution - haemostasis - microvesicles - endothelium - blood platelets

Full Text

References

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