title: Inflammatory and Vasoactive Effects of Serum Following Inhalation of Varied Complex Mixtures.
abstract: Chronic cardiovascular disease is associated with air pollution exposure in epidemiology and toxicology studies. Inhaled toxicants can induce changes in serum bioactivity that impact endothelial inflammatory gene expression in vitro and impair vasorelaxation ex vivo, which are common precursors to atherosclerosis. Comparisons between single pollutants and common combustion mixtures, in terms of driving such serum inflammatory and vasoactive effects, have not been characterized. Healthy C57BL/6 mice were exposed to a single 6-h period of contrasting pollutant atmospheres: road dust, mixed vehicle emissions (MVE; a combination of gasoline and diesel engine emissions) particulate matter, mixed vehicle emissions gases, road dust plus ozone, road dust plus MVE, and hardwood smoke. Serum obtained from mice 24 h after these exposures was used as a stimulus to assess inflammatory potential in two assays: incubated with primary murine cerebrovascular endothelial cells for 4 h to measure inflammatory gene expression or applied to naïve aortic rings in an ex vivo myographic preparation. Road dust and wood smoke exposures were most potent at inducing inflammatory gene expression, while MVE atmospheres and wood smoke were most potent at impairing vasorelaxation to acetylcholine. Responses are consistent with recent reports on MVE toxicity, but reveal novel serum bioactivity related to wood smoke and road dust. These studies suggest that the compositional changes in serum and resultant bioactivity following inhalation exposure to pollutants may be highly dependent on the composition of mixtures.
authors.affiliation: College of Pharmacy, University of New Mexico, MSC09 5360, 1, Albuquerque, NM, 87131, USA.
authors.forename: Mario J
authors.initials: MJ
authors.lastname: Aragon
authors.affiliation: Brigham and Women's Hospital, Boston, MA, USA.|Lovelace Respiratory Research Institute, Albuquerque, NM, USA.
authors.forename: Izabela
authors.initials: I
authors.lastname: Chrobak
authors.affiliation: Lovelace Respiratory Research Institute, Albuquerque, NM, USA.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Brower
authors.affiliation: College of Pharmacy, University of New Mexico, MSC09 5360, 1, Albuquerque, NM, 87131, USA.
authors.forename: Luis
authors.initials: L
authors.lastname: Roldan
authors.affiliation: Brigham and Women's Hospital, Boston, MA, USA.|Lovelace Respiratory Research Institute, Albuquerque, NM, USA.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Fredenburgh
authors.affiliation: Lovelace Respiratory Research Institute, Albuquerque, NM, USA.
authors.forename: Jacob D
authors.initials: JD
authors.lastname: McDonald
authors.affiliation: College of Pharmacy, University of New Mexico, MSC09 5360, 1, Albuquerque, NM, 87131, USA. mcampen@unm.edu.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Campen
mesh_terms: D000393:Air Pollutants / Q000009:adverse effects / Q000633:toxicity*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D018836:Inflammation Mediators / Q000097:blood*; D019570:Inhalation Exposure / Q000009:adverse effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009924:Organ Culture Techniques; D052638:Particulate Matter / Q000008:administration & dosage / Q000633:toxicity*; D044967:Serum / Q000378:metabolism*; D014665:Vasodilator Agents / Q000494:pharmacology; D001335:Vehicle Emissions / Q000633:toxicity*
chemical_list: D000393:Air Pollutants; D018836:Inflammation Mediators; D052638:Particulate Matter; D014665:Vasodilator Agents; D001335:Vehicle Emissions
keywords: Cardiovascular; Diesel; Endothelium; Exhaust; Gasoline; Particulate matter; Wood smoke