Study Suggests Unregulated Nano-sized Ultrafine Particles May Be Most Damaging Component of Air Pollution for Heart Disease
A new study indicates that ultrafine particles—particles of less than 0.18 micrometers—from vehicle emissions may be the most damaging components of air pollution in triggering plaque buildup in the arteries, which can lead to heart attack and stroke. The findings appear in an open access article in the 17 January online edition of the journal Circulation Research.
A team from University of California, Los Angeles (UCLA); the University of Southern California; the University of California, Irvine; and Michigan State University contributed to the research, which was led by Dr. Andre Nel, UCLA’s chief of nanomedicine. The study was primarily funded by the National Institute of Environmental Health Sciences and the US Environmental Protection Agency (EPA).
It appears that the smallest air pollutant particles, which are the most abundant in an urban environment, are the most toxic. This is the first study that demonstrates the ability of nano-sized air pollutants to promote atherosclerosis in an animal model.—Dr. Jesus Araujo, first author and assistant professor of medicine and director of environmental cardiology at the David Geffen School of Medicine at UCLA
The EPA currently regulates fine particles at 2.5 micrometers, but doesn’t monitor particles in the nano- or ultrafine range. These particles are too small to capture in a filter, so new technology must be developed to track their contribution to adverse health effects.
We hope our findings offer insight into the impact of nano-sized air pollutant particles and help explore ways for stricter air quality regulatory guidelines.—Andre Nel
The UCLA research team previously reported that diesel exhaust particles interact with artery-clogging fats in low-density lipoprotein (LDL) cholesterol to activate genes that cause the blood-vessel inflammation that can lead to heart disease. (Earlier post.)
In the current study, researchers exposed mice with high cholesterol to one of two sizes of air pollutant particles from downtown Los Angeles freeway emissions and compared them with mice that received filtered air that contained very few particles.
The study, conducted over a five-week period, required a complex exposure design that was developed by teams led by Dr. Michael Kleinman, professor of community and environmental medicine at UC Irvine, and Dr. Constantinos Sioutas, professor of civil and environmental engineering at USC.
Researchers found that mice exposed to ultrafine particles exhibited 55% greater atherosclerotic-plaque development than animals breathing filtered air and 25% greater plaque development than mice exposed to fine-sized particles.
Pollutant particles are coated in chemicals sensitive to free radicals, which cause the cell and tissue oxidation. Oxidation leads to the inflammation that causes clogged arteries. Samples from polluted air revealed that ultrafine particles have a larger concentration of these chemicals and a larger surface area where these chemicals thrive, compared with larger particles, Sioutas noted.
Ultrafine particles may deliver a much higher effective dose of injurious components, compared with larger pollutant particles.—Andre Nel
Scientists also identified a key mechanism behind how these air pollutants are able to affect the atherosclerotic process. Using a test developed by Dr. Mohamad Navab, study co-author and a UCLA professor of medicine, researchers found that exposure to air pollutant particles significantly decreased the anti-inflammatory protective properties of HDL cholesterol.
To explore if air particle exposure caused oxidative stress throughout the body—which is an early process triggering the inflammation that causes clogged arteries—researchers checked for an increase in genes that would have been activated to combat this inflammatory progression.
They found greater levels of gene activation in mice exposed to ultrafine particles, compared to the other groups. The next step will be to develop a biomarker that could enable physicians to assess the degree of cardiovascular damage caused by air pollutants or measure the level of risk encountered by an exposed person.
Previous studies assessing the cardiovascular impact of air pollution have taken place over longer periods of exposure time, such as five to six months. The current study demonstrated that ill effects can occur more quickly, in just five weeks.
The research team included investigators from the fields of nanomedicine, cardiology and genetics. Additional co-authors included Berenice Barajas, Xuping Wang, Brian J. Bennett and Ke Wei Gong of the David Geffen School of Medicine at UCLA, and Jack Harkema from the department of pathobiology and diagnostic investigation at Michigan State University.
Additional grant support was provided by the National Institute of Allergy and Infectious Diseases; the National Heart, Lung and Blood Institute; and the Robert Wood Johnson Foundation.
Jesus A. Araujo et. al. Ambient Particulate Pollutants in the Ultrafine Range Promote Early Atherosclerosis and Systemic Oxidative Stress. Circ. Res. published online Jan 17, 2008
Andre Nel, Tian Xia, Lutz Mädler, Ning Li. Toxic Potential of Materials at the Nanolevel. Science 3 February 2006: Vol. 311. no. 5761, pp. 622 - 627 DOI: 10.1126/science.1114397