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

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.

Exploring the mitochondrial microRNA import pathway through Polynucleotide Phosphorylase (PNPase)

“…Patients were characterized as non-diabetic or type 2 diabetic based on a previous medical diagnosis of type 2 diabetes mellitus. Pericardial fat was trimmed from right atrial appendage samples and mitochondria isolated as previously described [8,9,22–26,65,67,88,95]. …”

“…At approximately 20–22 weeks of age, db/db mice and littermate controls were euthanized, hearts excised and cardiac mitochondrial subpopulations were isolated for analyses as previously described following the methods of Palmer et al [67] with minor modifications by our laboratory [8,9,22,24–26,65,88]. After isolation of mitochondrial subpopulations from both animal and human cardiac tissue, SSM and IFM were further purified by percoll gradient (23%, 15%, 10% and 3% percoll solution).…”

“…SDS-PAGE was run on 4–12% gradient gels, as previously described [8,9,24,56,65,88,95] with modifications. For assessment of protein content, equal amounts of protein were loaded as determined by the Brad-ford method using bovine serum albumin as a standard as previously described [17].…”

Systematic review of community health impacts of mountaintop removal mining

“…Two studies of adult rats reported impaired microvascular function and impacts on cardiac mitochondrial function after intratracheal exposure to the same mixture of PM collected in the vicinity of MTR-mining sites (Knuckles et al 2013; Nichols et al 2015). Cytotoxicity and impaired cell proliferation and migration were reported in a human bronchial cell line exposed to MTR-mining PM, and transplantation of these cells into mice promoted tumor growth of co-transplanted human lung carcinoma H460 cells (Luanpitpong et al 2014).…”

Ultrafine Particulate Matter Increases Cardiac Ischemia/Reperfusion Injury via Mitochondrial Permeability Transition Pore

“…One study has linked fine PM exposure to multiple forms of mitochondrial dysfunction, including cardiomyocte mitochondrial structure changes, changes in mitochondrial fusion/fission gene expression, and reduction in the activity of superoxide dismutase (19–21). Additionally, exposure to PM generated from mountain top removal mining was associated with increased susceptibility to opening of the mPTP (mitochondrial permeability transition pore) and thus induction of apoptotic pathways and cell death (22). …”