title: Thrombogenic changes in young and old mice upon subchronic exposure to air pollution in an urban roadside tunnel.
abstract: 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.
authors.affiliation: Center for Molecular and Vascular Biology, University of Leuven, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Emmerechts
authors.forename: Vanessa
authors.initials: V
authors.lastname: De Vooght
authors.forename: Steven
authors.initials: S
authors.lastname: Haenen
authors.forename: Serena
authors.initials: S
authors.lastname: Loyen
authors.forename: Soetkin
authors.initials: S
authors.lastname: Van kerckhoven
authors.forename: Bianca
authors.initials: B
authors.lastname: Hemmeryckx
authors.forename: Jeroen A J
authors.initials: JA
authors.lastname: Vanoirbeek
authors.forename: Peter H
authors.initials: PH
authors.lastname: Hoet
authors.forename: Ben
authors.initials: B
authors.lastname: Nemery
authors.forename: Marc F
authors.initials: MF
authors.lastname: Hoylaerts
mesh_terms: D000375:Aging / Q000097:blood; D000397:Air Pollution / Q000009:adverse effects*; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001772:Blood Cell Count; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D005169:Factor VIII / Q000378:metabolism; D006487:Hemostasis; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D008168:Lung / Q000098:blood supply / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018986:Motor Vehicles; D019007:P-Selectin / Q000378:metabolism; D052638:Particulate Matter / Q000009:adverse effects; D010976:Platelet Count; D012307:Risk Factors; D013927:Thrombosis / Q000097:blood / Q000209:etiology*; D014504:Urban Health; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D015415:Biomarkers; D015850:Interleukin-6; D019007:P-Selectin; D052638:Particulate Matter; D014841:von Willebrand Factor; D005169:Factor VIII