Kristen Cosselman is investigating the acute effects of diesel air pollution on cardiovascular health.Photo:
Kristen Cosselman is investigating the acute effects of diesel air pollution on cardiovascular health, specifically biological mechanisms during and immediately after exposure. She recently received a highly competitive two-year $50,000 predoctoral fellowship from the American Heart Association to support her research.
“If researchers can identify some of the major mechanisms, then it will be much easier to advance prevention,” said Cosselman, who is a doctoral student studying environmental toxicology in our department and working with Professor Joel Kaufman.
Traffic-related air pollution is most commonly perceived by the public as a respiratory problem. However, numerous studies have shown that the most significant effects of exposure are on cardiovascular health. The World Health Organization estimates that 80% of deaths attributed to outdoor air pollution are due to heart disease and stroke. What remains unclear are the biological mechanisms stimulated by exposure that lead to these adverse outcomes.
For her master’s degree, Cosselman found that exposure to diesel exhaust (200 µg/m3) led to blood pressure increases—about 5 mmHg—within the first 30-90 minutes of exposure in young, healthy people, aged 18-49 years of age. While the change was minor for someone young and healthy, Cosselman explained, the increase might push a person with atherosclerosis or heart disease into a “danger zone,” particularly if the person is more susceptible to a rupture in plaque build-up in an artery.
“The blood pressure increase could underlie some of the outcomes we see in the larger cohort studies—such as heart attack or stroke,” she said. On a population-wide basis, small exposure-related increases could shift large groups of people into risky levels of blood pressure.
Cosselman’s current study is one of the first to combine cellular markers with clinical measures in a single controlled environment, and to take advantage of new technologies for realistic exposure modeling.
Twenty volunteer study participants, aged 18-49 years, have one of three variations of a single gene called TRPV1 that plays a role in the pathway the body uses to sense irritants—from hot peppers to noxious fumes. She is testing both physiological and biological responses stratified by gene variation to uncover the role of this pathway in the response to inhaled pollutants.
At each session, spaced three or more weeks apart, the volunteers are either given a placebo or a sympathetic nervous system blocker used to treat high blood pressure. The volunteers spend two hours in a specialized controlled exposure facility that provides either filtered air or diluted diesel exhaust (a model for traffic-related air pollution) at 300 µg/m3 of PM2.5, a level much higher than air pollution in Seattle, but lower than the levels measured in Beijing and other rapidly developing international mega-cities. An occupation like underground mining has similarly high exposures. The subject’s blood pressure is monitored before, during, and after exposure for 24 hours. Measuring the difference in blood pressure after the participant is treated with the pharmaceutical tests another mechanism involved in the biological response to exposure.
To understand which genes in the respiratory and cardiovascular systems are firing up or shutting down in response to diesel exposure, Cosselman has two simultaneous in vitro experiments that incorporate the controlled exposure chamber and blood drawn from the study participants.
To investigate early effects that most likely initiate in the lung, human respiratory cells are exposed to the same type of air that study participants receive—filtered or diesel-exhaust-enriched air. This experiment uses a newly developed device to help pollution land directly on cells to be studied. This approach is a major improvement over toxicological models which “dump” materials collected on filters into cell-culture media. Cosselman’s studies more accurately mirror how the lungs experience pollution because her approach involves depositing the ultrafine aerosolized particles directly onto the cells.
In another set of experiments, Cosselman will investigate mechanisms of the vascular response using a model that utilizes coronary artery cells and blood drawn from participants in the clinical study.
Taken together, this set of toxicology studies will add new information to what is known about how air pollution can affect cardiovascular diseases.
Cosselman plans to graduate in 2016.