title: Hazard identification of particulate matter on vasomotor dysfunction and progression of atherosclerosis.
abstract: The development and use of nanoparticles have alerted toxicologists and regulators to issues of safety testing. By analogy with ambient air particles, it can be expected that small doses are associated with a small increase in risk of cardiovascular diseases, possibly through oxidative stress and inflammatory pathways. We have assessed the effect of exposure to particulate matter on progression of atherosclerosis and vasomotor function in humans, animals, and ex vivo experimental systems. The type of particles that have been tested in these systems encompass TiO(2), carbon black, fullerene C(60), single-walled carbon nanotubes, ambient air particles, and diesel exhaust particles. Exposure to ambient air particles is associated with accelerated progression of atherosclerosis and vasomotor dysfunction in both healthy and susceptible animal models and humans at risk of developing cardiovascular diseases. The vasomotor dysfunction includes increased vasoconstriction as well as reduced endothelium-dependent vasodilatation; endothelium-independent vasodilatation is often unaffected indicating mainly endothelial dysfunction. Pulmonary exposure to TiO(2), carbon black, and engineered nanoparticles generate vasomotor dysfunction; the effect size is similar to that generated by combustion-derived particles, although the effect could depend on the exposure period and the administered dose, route, and mode. The relative risk associated with exposure to nanoparticles may be small compared to some traditional risk factors for cardiovascular diseases, but superimposed on these and possible exposure to large parts of the population it is a significant public health concern. Overall, assessment of vasomotor dysfunction and progression of atherosclerosis are promising tools for understanding the effects of particulate matter.
authors.affiliation: Department of Public Health, Section of Environmental Health, University of Copenhagen, Øster Farimagsgade 5A, DK-1014 Copenhagen K, Denmark. pemo@sund.ku.dk
authors.forename: Peter
authors.initials: P
authors.lastname: Møller
authors.forename: Lone
authors.initials: L
authors.lastname: Mikkelsen
authors.forename: Lise Kristine
authors.initials: LK
authors.lastname: Vesterdal
authors.forename: Janne Kjærsgaard
authors.initials: JK
authors.lastname: Folkmann
authors.forename: Lykke
authors.initials: L
authors.lastname: Forchhammer
authors.forename: Martin
authors.initials: M
authors.lastname: Roursgaard
authors.forename: Pernille Høgh
authors.initials: PH
authors.lastname: Danielsen
authors.forename: Steffen
authors.initials: S
authors.lastname: Loft
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D050197:Atherosclerosis / Q000453:epidemiology* / Q000473:pathology; D001808:Blood Vessels / Q000187:drug effects / Q000473:pathology; D018450:Disease Progression; D006801:Humans; D053758:Nanoparticles / Q000633:toxicity; D052638:Particulate Matter / Q000633:toxicity*; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D014666:Vasomotor System / Q000187:drug effects* / Q000473:pathology
chemical_list: D000393:Air Pollutants; D052638:Particulate Matter