Cardiac and mitochondrial dysfunction following acute pulmonary exposure to mountaintop removal mining particulate matter.
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 (PM MTM). To address this question, we exposed male Sprague-Dawley rats to PM MTM, 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. PM MTM exposure elicited a significant decrease in ejection fraction and fractional shortening compared with controls. Investigation into the cellular impacts of PM MTM 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 PM MTM 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.
West Virginia University School of Medicine, Division of Exercise Physiology, Morgantown, West Virginia; Center for Cardiovascular and Respiratory Sciences, Morgantown, West Virginia;
Cody E
CE
Nichols
West Virginia University School of Medicine, Division of Exercise Physiology, Morgantown, West Virginia; Center for Cardiovascular and Respiratory Sciences, Morgantown, West Virginia;
Danielle L
DL
Shepherd
Center for Cardiovascular and Respiratory Sciences, Morgantown, West Virginia; West Virginia University, School of Public Health, Morgantown, West Virginia;
Travis L
TL
Knuckles
West Virginia University School of Medicine, Division of Exercise Physiology, Morgantown, West Virginia; Center for Cardiovascular and Respiratory Sciences, Morgantown, West Virginia;
Dharendra
D
Thapa
Center for Cardiovascular and Respiratory Sciences, Morgantown, West Virginia;
Janelle C
JC
Stricker
Center for Cardiovascular and Respiratory Sciences, Morgantown, West Virginia; West Virginia University, Department of Physiology and Pharmacology, Morgantown, West Virginia;
Phoebe A
PA
Stapleton
Center for Cardiovascular and Respiratory Sciences, Morgantown, West Virginia; West Virginia University, Department of Physiology and Pharmacology, Morgantown, West Virginia;
Valerie C
VC
Minarchick
West Virginia University, Department of Physiology and Pharmacology, Morgantown, West Virginia; National Institute for Occupational Safety and Health, Morgantown, West Virginia.
Aaron
A
Erdely
West Virginia University, Department of Physiology and Pharmacology, Morgantown, West Virginia; National Institute for Occupational Safety and Health, Morgantown, West Virginia.
Patti C
PC
Zeidler-Erdely
West Virginia University School of Medicine, Division of Exercise Physiology, Morgantown, West Virginia; Center for Cardiovascular and Respiratory Sciences, Morgantown, West Virginia;
Stephen E
SE
Alway
Center for Cardiovascular and Respiratory Sciences, Morgantown, West Virginia; West Virginia University, Department of Physiology and Pharmacology, Morgantown, West Virginia;
Timothy R
TR
Nurkiewicz
West Virginia University School of Medicine, Division of Exercise Physiology, Morgantown, West Virginia; Center for Cardiovascular and Respiratory Sciences, Morgantown, West Virginia; jhollander@hsc.wvu.edu.
John M
JM
Hollander
D000395:Air Pollutants, Occupational / Q000633:toxicity*; D000397:Air Pollution / Q000009:adverse effects*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000378:metabolism; D004452:Echocardiography; D004781:Environmental Exposure; D004784:Environmental Monitoring; D006331:Heart Diseases / Q000139:chemically induced* / Q000000981:diagnostic imaging; D020287:In Situ Nick-End Labeling; D007278:Injections, Spinal; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D028361:Mitochondrial Diseases / Q000139:chemically induced* / Q000000981:diagnostic imaging; D009200:Myocardial Contraction / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D052638:Particulate Matter / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000395:Air Pollutants, Occupational; D052638:Particulate Matter; D020169:Caspases
apoptosis; cardiac function; mitochondria; particulate matter