Science Inventory

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

Citation:

Holland, N., C. Frasier, R. Sloan, R. Devlin, D. Brown, AND C. Wingard. Ultrafine Particulate Matter Increases Cardiac Ischemia/Reperfusion Injury via Mitochondrial Permeability Transition Pore. Cardiovascular Toxicology. Humana Press Incorporated, Totowa, NJ, 17(4):441-450, (2017).

Impact/Purpose:

This manuscript describes mechanisms by which ultrafine PM affects cardiac function, arrhythmogenesis, and ischemia/reperfusion using a rodent ex vivo model. It provides biological plausibility to support epidemiology studies that show ultrafine particles are especially potent in causing adverse cardiac outcomes.

Description:

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 intratracheal instillation of 100 g 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 changes to overall cardiac function or major changes in arrhythmogenesis. Cardiac I/R injury was attenuable with administration of 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 associated 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.

Record Details:

Record Type: DOCUMENT ( JOURNAL/ PEER REVIEWED JOURNAL)
Product Published Date: 10/01/2017
Record Last Revised: 04/11/2018
OMB Category: Other
Record ID: 337777