DERT Stories of Success
Gokhan Mutlu M.D.
People with underlying cardiovascular disease who are exposed to air pollution are at greater risk for developing strokes or heart attacks. Pulmonologist Gokhan Mutlu, M.D., has a longstanding interest in investigating how air pollution causes harm to the lungs and triggers life threatening cardiovascular issues, such as blood clots. His research could lead to new therapies for preventing cardiovascular problems related to air pollution.
Mutlu’s research focuses on particulate matter (PM) air pollution. This complex mixture contains acids, metals, and dusts that can be inhaled and enter the lungs and blood stream. Research shows that deaths associated with acute exposure to ambient PM are largely due to cardiovascular events such as restricted blood flow.
Mutlu’s expertise was recognized by his 2013 election to the American Society of Clinical Investigation, followed by a promotion to professor and chief of pulmonary and critical care medicine at the University of Chicago in 2014. He first became interested in pulmonology while working with intensive care patients during his residency, and his later interest in environmental health was sparked by collaborations with researchers like NIEHS grantee, G.R. Scott Budinger, M.D., who wanted to explore how PM causes injury to lung cells and tissues. In later experiments, Mutlu and Budinger noticed blood-clotting in the lungs of mice exposed to PM. These collaborative findings led to Mutlu’s 2006 NIEHS Outstanding New Environmental Scientist (ONES) award to further explore the mechanisms of airborne PM-induced blood clots, or thrombosis.
Research Suggests PM-Induced Stress and Inflammation are Associated with Blood Clotting
Mutlu’s research using mice suggests a role for oxidative stress and inflammation in PM-induced blood clots. Mutlu and colleagues found that PM-exposed mice release a pro-inflammatory protein called interleukin-6 (IL-6) from their lung immune cells. The presence of IL-6 and lung immune cells was also associated with accelerated formation of arterial blood clots.
Mutlu and colleagues also discovered a potential role for the sympathetic nervous system – which is responsible for the body’s “fight or flight” responses to stimuli – in mediating effects of PM. Mice exposed to PM showed elevated levels of stress hormones that are released as a result of PM-induced fight or flight response. These stress hormones target cell receptors, such as beta adrenergic receptors, which Mutlu’s research has shown may be associated with blood clotting. His experiments showed that PM-exposed mice lacking these stress hormones had a diminished IL-6 response and a reduced tendency toward blood clot formation. Furthermore, treating mice with non-selective beta (receptor) blockers prior to PM exposure also resulted in reduced blood clot formation.
“Our results suggest the pharmaceutical potential of non-selective beta blockers for preventing PM-induced thrombosis in patients with underlying heart disease,” Mutlu said.
Moving forward, Mutlu and his colleagues will continue to expand their findings and identify other PM-induced mechanisms using lung immune cells collected from healthy humans and mice. For example, Mutlu plans to explore how PM-induced oxidative stress affects epigenetic changes in lung immune cells.
“Many medical professionals including pulmonologists and cardiologists are truly unaware of the link between air pollution and cardiovascular health – this means that they are unable to inform patients about prevention and the significance of avoiding areas with elevated levels of air pollution,” Mutlu explained. He says that environmental health scientists can reach health care professionals by increasing the visibility of environmental health through grant opportunities, publishing more articles on the topic in high impact medical journals, and forming groups within medical societies who advocate for environmental health education.