Cardiac and mitochondrial dysfunction following acute pulmonary exposure to mountaintop removal mining particulate matter

Cody E. Nichols, Danielle L. Shepherd, Travis L. Knuckles, Dharendra Thapa, Janelle C. Stricker, Phoebe A. Stapleton, Valerie C. Minarchick, Aaron Erdely, Patti C. Zeidler-Erdely, Stephen Alway, Timothy R. Nurkiewicz, John M. Hollander

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Throughout the United States, air pollution correlates with adverse health outcomes, and cardiovascular disease incidence is commonly increased following environmental exposure. In areas surrounding active mountaintop removal mines (MTM), a further increase in cardiovascular morbidity is observed and may be attributed in part to particulate matter (PM) released from the mine. The mitochondrion has been shown to be central in the etiology of many cardiovascular diseases, yet its roles in PM-related cardiovascular effects are not realized. In this study, we sought to elucidate the cardiac processes that are disrupted following exposure to mountaintop removal mining particulate matter (PMMTM). To address this question, we exposed male Sprague-Dawley rats to PMMTM, collected within one mile of an active MTM site, using intratracheal instillation. Twenty-four hours following exposure, we evaluated cardiac function, apoptotic indices, and mitochondrial function. PMMTM exposure elicited a significant decrease in ejection fraction and fractional shortening compared with controls. Investigation into the cellular impacts of PMMTM exposure identified a significant increase in mitochondrial-induced apoptotic signaling, as reflected by an increase in TUNEL-positive nuclei and increased caspase-3 and-9 activities. Finally, a significant increase in mitochondrial transition pore opening leading to decreased mitochondrial function was identified following exposure. In conclusion, our data suggest that pulmonary exposure to PMMTM increases cardiac mitochondrial-associated apoptotic signaling and decreases mitochondrial function concomitant with decreased cardiac function. These results suggest that increased cardiovascular disease incidence in populations surrounding MTM mines may be associated with increased cardiac cell apoptotic signaling and decreased mitochondrial function.

Original languageEnglish (US)
Pages (from-to)H2017-H2030
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume309
Issue number12
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

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Particulate Matter
Cardiovascular Diseases
Lung
Caspase 9
Incidence
Air Pollution
Environmental Exposure
In Situ Nick-End Labeling
Caspase 3
Sprague Dawley Rats
Mitochondria
Morbidity
Health
Population

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Cardiac and mitochondrial dysfunction following acute pulmonary exposure to mountaintop removal mining particulate matter. / Nichols, Cody E.; Shepherd, Danielle L.; Knuckles, Travis L.; Thapa, Dharendra; Stricker, Janelle C.; Stapleton, Phoebe A.; Minarchick, Valerie C.; Erdely, Aaron; Zeidler-Erdely, Patti C.; Alway, Stephen; Nurkiewicz, Timothy R.; Hollander, John M.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 309, No. 12, 01.01.2015, p. H2017-H2030.

Research output: Contribution to journalArticle

Nichols, CE, Shepherd, DL, Knuckles, TL, Thapa, D, Stricker, JC, Stapleton, PA, Minarchick, VC, Erdely, A, Zeidler-Erdely, PC, Alway, S, Nurkiewicz, TR & Hollander, JM 2015, 'Cardiac and mitochondrial dysfunction following acute pulmonary exposure to mountaintop removal mining particulate matter', American Journal of Physiology - Heart and Circulatory Physiology, vol. 309, no. 12, pp. H2017-H2030. https://doi.org/10.1152/ajpheart.00353.2015
Nichols, Cody E. ; Shepherd, Danielle L. ; Knuckles, Travis L. ; Thapa, Dharendra ; Stricker, Janelle C. ; Stapleton, Phoebe A. ; Minarchick, Valerie C. ; Erdely, Aaron ; Zeidler-Erdely, Patti C. ; Alway, Stephen ; Nurkiewicz, Timothy R. ; Hollander, John M. / Cardiac and mitochondrial dysfunction following acute pulmonary exposure to mountaintop removal mining particulate matter. In: American Journal of Physiology - Heart and Circulatory Physiology. 2015 ; Vol. 309, No. 12. pp. H2017-H2030.
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