Center investigators are exploring links between diesel exhaust exposure and several chronic diseases.
Our Center has been researching respiratory susceptibility since the Center was founded in 1995. For the first eight years, we focused primarily on air pollution and asthma. In 2003, we began to look at how environmental factors can increase the risk of other conditions, such as cardiopulmonary and cardiovascular diseases.
The public health impacts of cardiopulmonary and cardiovascular disease are huge. Atherosclerosis, the buildup of cholesterol and fats in the coronary arteries that supply blood to the heart, is the #1 killer of both men and women in the United States.1 In recent years, it has become clear that environmental factors play a major role in the risk of cardiovascular disease, and that these factors could potentially be modified to reduce risk. The Center’s Cardiovascular Toxicology Area of Research Emphasis (ARE) brings together several researchers who are working in this promising field.
Cardiovascular toxicology is the study of the adverse health effects of toxic chemicals on the heart or blood systems. An important component of cardiovascular toxicology is identifying the exact mechanisms by which chemicals cause harm to the body. Several CEEH investigators are exploring possible mechanisms using engineered animal models. For example, ongoing projects in the Cardiovascular Toxicology ARE explore the roles of genetic susceptibility and gene expression in an effort to understand precisely how ambient particulate matter can contribute to cardiovascular and pulmonary diseases. Particulate matter refers to the complex mixture of very small particles and liquid droplets present in air.
Dr. Michael Chin
One example of this research is a study of diesel engine exhaust exposure, epigenetic changes and heart failure in mice. The project began as a CEEH Pilot Project Award in 2013, led by Cardiovascular Toxicology ARE researcher and cardiologist Dr. Michael Chin. The Center funds four to six small pilot projects each year. Pilot project grants are designed to help investigators to obtain preliminary data that will be useful for competitive, full-scale grant applications. CEEH has awarded a total of 74 pilots since 1995, investing approximately $1.85 million to date in these small, innovative research projects.
Dr. Chin and his team, which included Chad Weldy, Yonggang Liu, Yi-Chi Chang, Ivan Medvedev, Julie R Fox, Timothy Larson, and Wei-Ming Chien, studied exposure to diesel exhaust (DE) because DE is the greatest source of traffic-related fine particulate air pollution. Exposure to DE has been shown to be associated with an increased risk of cardiovascular disease and death. However, little research has been done on the potential long-term effects of exposure to DE in the womb (in utero) and during early development. Dr. Chin and his team wanted to know if in utero and very early life exposures could increase susceptibility to heart disease later in life.
To explore this question, the research team exposed mice to either filtered air or DE only during in utero and early life development. The researchers found that when the mice exposed to DE were raised to adulthood, they were significantly more susceptible to heart failure. Following a surgery to induce heart failure, these mice showed greater enlargement of the heart, worse contractile function, extensive fibrosis (build up of scar tissue within the heart), and lung congestion. They also showed a change in the inflammatory response in the lung, suggesting that environmental challenges during these developmental windows may be important not just to the heart, but also to the lungs.
Dr. Chad Weldy enjoys a rare moment away from the lab.
The researchers concluded that exposure to diesel exhaust air pollution in utero and in early life increases susceptibility to heart failure in adult mice. These results suggest that the effects of air pollution on cardiovascular disease in humans may originate from very early life exposures.2
A more recent paper in PLoS ONE links in utero exposure to DE to weight gain and changes in blood pressure, as well as increased risk of heart failure.3
Dr. Chad Weldy, Senior Fellow within the Division of Cardiology and lead author, says: “This work expands our understanding of how environmental exposures during early life development contribute to disease. As we learn that in utero development is critical for setting adult health, we need to further investigate how common environmental exposures may adversely impact development and increase lifelong risk of disease. I hope to see this work continue as epidemiological studies, where we can determine if these effects we see in the lab are also occurring in human populations. These future studies may prove to be crucial for setting regulatory policy, reducing environmental exposures, and improving public health.”
References:
- http://www.nhlbi.nih.gov/health/health-topics/topics/atherosclerosis/atrisk.html.
- Weldy CS, Liu Y, Chang YC, Medvedev IO, Fox JR, Larson TV, Chien WM, Chin MT. In utero and early life exposure to diesel exhaust air pollution increases adult susceptibility to heart failure in mice. Particle and fibre toxicology. 2013;10(1):59. Epub 2013/11/28. doi: 10.1186/1743-8977-10-59. PubMed PMID: 24279743.
- Weldy CS, Liu Y, Liggitt HD, Chin MT (2014) In Utero Exposure to Diesel Exhaust Air Pollution Promotes Adverse Intrauterine Conditions, Resulting in Weight Gain, Altered Blood Pressure, and Increased Susceptibility to Heart Failure in Adult Mice. PLoS ONE 9(2): e88582. doi:10.1371/journal.pone.0088582