Student Research: Lisa Marie Smith

, Environmental Toxicology (Tox), 2004
Faculty Advisor: Daniel L. Luchtel

Effects and Mechanisms of Cardiopulmonary Toxicity of Seattle Particulate Matter in the Apolipoprotein E Knockout Transgenic Mouse


Background: The American Lung Association reports that 55% of Americans live in areas were their health is threatened by air pollution (ALA, 2004). The individuals most at risk for the detrimental effects of air pollution are the elderly and people with preexisting cardiovascular disease (CVD). In King County alone, there are 182,840 people over age 65 and 370,867 individuals with CVD (ALA, 2004). Particulate matter (PM) from Seattle has a unique composition, mainly due to the influence of wood smoke, yet its health effects have not been examined. This study examines the effects of Seattle PM on the apolipoprotein E knockout (apoE-/-) mouse, a model of CVD. Toxic mechanisms are also studied through the use of Microarray technology.

Methods: Lung Lavage—Aged male apoE-/- and C57BL/6J mice were oro-pharyngeally exposed to 0, 50, 150, or 400 mg of Seattle PM and sacrificed at, 24, or 72 hours post-exposure. Lung Lavage total and differential cell counts were used to determine does response and time course parameters.
Electrocardiogram—Aged male apoE-/- mice were implanted with telemetry devices and exposed to 50mg Seattle PM to determine the effect on heart rate variability (HRV) for four days.
Microarray—Lung and heart tissue from the dose-response experiment were examined for gene up-and down-regulation in an array of 20,000 genes are per manufacturers instructions.

Results: The apoE-/- mouse showed a divergent response to Seattle PM as compared to the C57BL/6J mouse as a differential dose and time based response was evident. There was a significant decrease in all HRV measurements, which has been used as a significant predictor of overall mortality in comprised individuals (Task Force, 1996). The microarray data indicated the activation of several pathways of cardiopulmonary pathophysiology.

Conclusion: The apoE-/- mouse may be an appropriate model in which to test the effects of PM. The HRV data suggest that Seattle PM causes a decrease in parasympathetic tone which may lead to myocardial ischemia and fatal arrhythmias. While, Seattle PM has unique toxic characteristics, the results of this study are likely to be applicable to PM from different sources/locales. While the overall mechanism of PM toxicity remains unknown, the present study provides insight into pathophysiology pathways and susceptibility.