title: The role of particulate matter-associated zinc in cardiac injury in rats.
abstract: BACKGROUND
  Exposure to particulate matter (PM) has been associated with increased cardiovascular morbidity; however, causative components are unknown. Zinc is a major element detected at high levels in urban air.
  
  
  OBJECTIVE
  We investigated the role of PM-associated zinc in cardiac injury.
  
  
  METHODS
  We repeatedly exposed 12- to 14-week-old male Wistar Kyoto rats intratracheally (1x/week for 8 or 16 weeks) to a) saline (control); b) PM having no soluble zinc (Mount St. Helens ash, MSH); or c) whole-combustion PM suspension containing 14.5 microg/mg of water-soluble zinc at high dose (PM-HD) and d ) low dose (PM-LD), e) the aqueous fraction of this suspension (14.5 microg/mg of soluble zinc) (PM-L), or f ) zinc sulfate (rats exposed for 8 weeks received double the concentration of all PM components of rats exposed for 16 weeks).
  
  
  RESULTS
  Pulmonary inflammation was apparent in all exposure groups when compared with saline (8 weeks > 16 weeks). PM with or without zinc, or with zinc alone caused small increases in focal subepicardial inflammation, degeneration, and fibrosis. Lesions were not detected in controls at 8 weeks but were noted at 16 weeks. We analyzed mitochondrial DNA damage using quantitative polymerase chain reaction and found that all groups except MSH caused varying degrees of damage relative to control. Total cardiac aconitase activity was inhibited in rats receiving soluble zinc. Expression array analysis of heart tissue revealed modest changes in mRNA for genes involved in signaling, ion channels function, oxidative stress, mitochondrial fatty acid metabolism, and cell cycle regulation in zinc but not in MSH-exposed rats.
  
  
  CONCLUSIONS
  These results suggest that water-soluble PM-associated zinc may be one of the causal components involved in PM cardiac effects.
authors.affiliation: National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27710, USA. kodavanti.urmila@epa.gov
authors.forename: Urmila P
authors.initials: UP
authors.lastname: Kodavanti
authors.forename: Mette C
authors.initials: MC
authors.lastname: Schladweiler
authors.forename: Peter S
authors.initials: PS
authors.lastname: Gilmour
authors.forename: J Grace
authors.initials: JG
authors.lastname: Wallenborn
authors.forename: Bhaskar S
authors.initials: BS
authors.lastname: Mandavilli
authors.forename: Allen D
authors.initials: AD
authors.lastname: Ledbetter
authors.forename: David C
authors.initials: DC
authors.lastname: Christiani
authors.forename: Marschall S
authors.initials: MS
authors.lastname: Runge
authors.forename: Edward D
authors.initials: ED
authors.lastname: Karoly
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Costa
authors.forename: Shyamal
authors.initials: S
authors.lastname: Peddada
authors.forename: Richard
authors.initials: R
authors.lastname: Jaskot
authors.forename: Judy H
authors.initials: JH
authors.lastname: Richards
authors.forename: Ronald
authors.initials: R
authors.lastname: Thomas
authors.forename: Nageswara R
authors.initials: NR
authors.lastname: Madamanchi
authors.forename: Abraham
authors.initials: A
authors.lastname: Nyska
mesh_terms: D000154:Aconitate Hydratase / Q000378:metabolism; D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D004249:DNA Damage; D004272:DNA, Mitochondrial / Q000235:genetics; D020869:Gene Expression Profiling; D006331:Heart Diseases / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D008929:Mitochondria, Heart / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D052638:Particulate Matter / Q000633:toxicity*; D051381:Rats; D011921:Rats, Inbred WKY; D015032:Zinc / Q000633:toxicity*
chemical_list: D000393:Air Pollutants; D004272:DNA, Mitochondrial; D052638:Particulate Matter; D000154:Aconitate Hydratase; D015032:Zinc