Lisa Marie Corey

Project title: Cardiovascular Effects of Diesel Exhaust in a Mouse Model of Cardiovascular Disease

Degree: PhD | Program: Environmental Toxicology (Tox) | Project type: Thesis/Dissertation
Completed in: 2008 | Faculty advisor: Daniel L. Luchtel


The cardiovascular system is exquisitely sensitive to adverse effects following increases in ambient particulate mater, as exemplified by increases in morbidity and mortality following periods of greater air pollution. This is especially true in the elderly and individuals with preexisting cardiovascular disease. Diesel accounts for a large percentage of particulate matter in an urban setting. Pulmonary inflation, systemic inflammation, and/or changes in autonomic function may be the cause of coronary artery events such as atherosclerotic plaque rupture, and thrombus and embolus formation in the cardiac vasculature. To evaluate the cardiovascular effects and mechanisms of diesel exhaust perturbations, we exposed 30 week old apoE-/- mice, a mouse model of cardiovascular disease, to filtered air, 200ug/m3 of diesel exhaust, or 400ug/m3 of diesel exhaust for 1 day, 3 days, 5 days, 4 weeks, or 8 weeks (n=10-15/dose/time). Additionally, we implanted 14 month old apoE-/- mice with radiotelemetrized electrocardiogram devices to monitor heart rate and heart rate variability during filtered air and exposure to 100, 200, or 400 ug/m3 diesel exhaust. Although there were few pulmonary markers of inflammation (bronchoalveolar Lavage cell totals, cell differentials, or cytokines), there were increases in the serum cytokines IL-10, GM-CSF, IL-1B, and IL-4 with high doses of diesel exhaust. Likewise there were increases in the heart rate variability time domain measures of SDNN and rMSSD. There were no changes atherosclerotic plaque size in the innominate artery. Taken together, these results suggest that a pulmonary response is not necessary to evoke a systemic response to diesel exhaust or that the pulmonary response is minimal enough to be measurable by the methods used in this study. Systemic cytokines are both markers and mediators of atherosclerotic disease and increases in heart rate variability parameters may indicate an increased likelihood of arrhythmia or myocardial infarction. Diesel exhaust inhalation causes increases in serum cytokines and heart rate variability parameters in both acute and chronic exposures in older mice with preexisting cardiovascular disease, a response which may be similar to human responses.