title: Ultrafine Particulate Matter Increases Cardiac Ischemia/Reperfusion Injury via Mitochondrial Permeability Transition Pore.
abstract: Ultrafine particulate matter (UFP) has been associated with increased cardiovascular morbidity and mortality. However, the mechanisms that drive PM-associated cardiovascular disease and dysfunction remain unclear. We examined the impact of oropharyngeal aspiration of 100 μg UFP from the Chapel Hill, NC, air shed in Sprague-Dawley rats on cardiac function, arrhythmogenesis, and cardiac ischemia/reperfusion (I/R) injury using a Langendorff working heart model. We found that exposure to UFP was capable of significantly exacerbating cardiac I/R injury without changing overall cardiac function or major changes in arrhythmogenesis. Cardiac I/R injury was attenuable with administration of cyclosporin A (CsA), suggesting a role for the mitochondrial permeability transition pore (mPTP) in UFP-associated cardiovascular toxicity. Isolated cardiac mitochondria displayed decreased Ca2+buffering before opening of the mPTP. These findings suggest that UFP-induced expansion of cardiac I/R injury may be a result of mPTP Ca2+sensitization resulting in increased mitochondrial permeability transition and potential initiation of mPTP-associated cell death pathways.
authors.affiliation: Department of Physiology, Brody School of Medicine, East Carolina University, Greenville, NC, USA.
authors.forename: Nathan A
authors.initials: NA
authors.lastname: Holland
authors.affiliation: Department of Physiology, Brody School of Medicine, East Carolina University, Greenville, NC, USA.
authors.forename: Chad R
authors.initials: CR
authors.lastname: Fraiser
authors.affiliation: Department of Physiology, Brody School of Medicine, East Carolina University, Greenville, NC, USA.
authors.forename: Ruben C
authors.initials: RC
authors.lastname: Sloan
authors.affiliation: National Health and Environmental Effects Research Laboratory, Environmental Public Health Division, US Environmental Protection Agency, Chapel Hill, NC, USA.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Devlin
authors.affiliation: Department of Physiology, Brody School of Medicine, East Carolina University, Greenville, NC, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Brown
authors.affiliation: Department of Physiology, Brody School of Medicine, East Carolina University, Greenville, NC, USA. cwingard@bellarmine.edu.|Lansing School of Nursing and Health Sciences, Physical Therapy Department, Bellarmine University, 2001 Newburg Rd, Louisville, KY, 40205, USA. cwingard@bellarmine.edu.
authors.forename: Christopher J
authors.identifier: 0000-0002-8251-5678
authors.initials: CJ
authors.lastname: Wingard
mesh_terms: D000818:Animals; D000067268:Isolated Heart Preparation / Q000379:methods; D008297:Male; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism*; D000083162:Mitochondrial Permeability Transition Pore; D015428:Myocardial Reperfusion Injury / Q000139:chemically induced* / Q000378:metabolism* / Q000503:physiopathology; D010316:Particle Size; D052638:Particulate Matter / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D052638:Particulate Matter
keywords: Cardiac; Mitochondria; Particulate matter; Reperfusion injury; mPTP