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The role of particulate matter-associated zinc in cardiac injury in rats.

Kodavanti UP, Schladweiler MC, Gilmour PS, Wallenborn JG, Mandavilli BS, Ledbetter AD, Christiani DC, Runge MS, Karoly ED, Costa DL, Peddada S, Jaskot R, Richards JH, Thomas R, Madamanchi NR, Nyska A - Environ. Health Perspect. (2008)

Bottom Line: We investigated the role of PM-associated zinc in cardiac injury.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.These results suggest that water-soluble PM-associated zinc may be one of the causal components involved in PM cardiac effects.

View Article: PubMed Central - PubMed

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

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.

Conclusion: These results suggest that water-soluble PM-associated zinc may be one of the causal components involved in PM cardiac effects.

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Related in: MedlinePlus

Heatmap showing differential gene expression as fold change intensities from group contrasts with saline control. Red and green color intensities indicate fold change increases and decreases, respectively, in gene expression (expressed as log2). Differentially expressed genes for MSH, PM-HD (whole particle suspension), and Zn relative to saline were grouped manually into functional categories.
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f7-ehp0116-000013: Heatmap showing differential gene expression as fold change intensities from group contrasts with saline control. Red and green color intensities indicate fold change increases and decreases, respectively, in gene expression (expressed as log2). Differentially expressed genes for MSH, PM-HD (whole particle suspension), and Zn relative to saline were grouped manually into functional categories.

Mentions: A very limited number (~ 21 non-EST) of genes showed small increases or decreases with MSH compared with saline controls [Figure 7; Supplemental Material, Table 1 (http://www.ehponline.org/members/2007/10379/suppl.pdf)]. These did not fall into one specific functional category. It should be noted that some of these changes might have occurred by chance alone. Genes commonly affected in MSH and PM-HD containing zinc (Figure 6) included cyclin-dependent kinase inhibitor 1A (decrease), protein tyrosine phosphatase receptor type M (increase), and a gene similar to hypothetical predicted protein CG003 (increase).


The role of particulate matter-associated zinc in cardiac injury in rats.

Kodavanti UP, Schladweiler MC, Gilmour PS, Wallenborn JG, Mandavilli BS, Ledbetter AD, Christiani DC, Runge MS, Karoly ED, Costa DL, Peddada S, Jaskot R, Richards JH, Thomas R, Madamanchi NR, Nyska A - Environ. Health Perspect. (2008)

Heatmap showing differential gene expression as fold change intensities from group contrasts with saline control. Red and green color intensities indicate fold change increases and decreases, respectively, in gene expression (expressed as log2). Differentially expressed genes for MSH, PM-HD (whole particle suspension), and Zn relative to saline were grouped manually into functional categories.
© Copyright Policy - public-domain
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2199289&req=5

f7-ehp0116-000013: Heatmap showing differential gene expression as fold change intensities from group contrasts with saline control. Red and green color intensities indicate fold change increases and decreases, respectively, in gene expression (expressed as log2). Differentially expressed genes for MSH, PM-HD (whole particle suspension), and Zn relative to saline were grouped manually into functional categories.
Mentions: A very limited number (~ 21 non-EST) of genes showed small increases or decreases with MSH compared with saline controls [Figure 7; Supplemental Material, Table 1 (http://www.ehponline.org/members/2007/10379/suppl.pdf)]. These did not fall into one specific functional category. It should be noted that some of these changes might have occurred by chance alone. Genes commonly affected in MSH and PM-HD containing zinc (Figure 6) included cyclin-dependent kinase inhibitor 1A (decrease), protein tyrosine phosphatase receptor type M (increase), and a gene similar to hypothetical predicted protein CG003 (increase).

Bottom Line: We investigated the role of PM-associated zinc in cardiac injury.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.These results suggest that water-soluble PM-associated zinc may be one of the causal components involved in PM cardiac effects.

View Article: PubMed Central - PubMed

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

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.

Conclusion: These results suggest that water-soluble PM-associated zinc may be one of the causal components involved in PM cardiac effects.

Show MeSH
Related in: MedlinePlus