UCLA Study Identifies Synergy Between Diesel Particles and Cholesterol in Enhancing Heart Disease
26 July 2007
A new UCLA study identifies a synergistic interaction between fine particles found in diesel exhaust and low-density lipoprotein (LDL) cholesterol that enhances vascular inflammation and atherosclerosis, significantly increasing the risk for heart attack and stroke.
Published in the 26 July edition of the online journal Genome Biology, the findings are the first to explain how fine particulate matter in air pollution works with artery-clogging fats to switch on the genes that cause blood vessel inflammation and lead to cardiovascular disease.
When you add one plus one, it normally totals two. But we found that adding diesel particles to cholesterol fats equals three. Their combination creates a dangerous synergy that wreaks cardiovascular havoc far beyond what’s caused by the diesel or cholesterol alone.—Dr. André Nel, chief of nanomedicine at the David Geffen School of Medicine at UCLA
The researchers set up a scenario to investigate the interaction between diesel exhaust particles and the fatty acids found in low-density lipoprotein (LDL) cholesterol—the “bad” type of cholesterol that leads to artery blockage.
In particular, the team was interested in how oxidation—cell and tissue damage resulting from exposure to molecules known as free radicals—contributes to inflammation and artery disease. Free radicals enter the body through small particles present in polluted air and are also byproducts of normal processes, such as the metabolic conversion of food into energy.
Diesel particles are coated in chemicals containing free radicals, and the fatty acids in LDL cholesterol generate free radicals during metabolism in the cells. We wanted to measure what happens when these two sources of oxidation come into contact.—Ke Wei Gong, UCLA
The scientists combined the pollutants and oxidized fats and cultured them with cells from the inner lining of human blood vessels. A few hours later, the team extracted DNA from the cells for genetic analysis.
They found that the diesel particles and oxidized fats worked in tandem to activate the genes that promote cellular inflammation. The interaction left a genetic footprint that reveals how interaction between the particles and cholesterol accelerates the narrowing and blockage of the blood vessels, according to Dr. Jesus Araujo, UCLA assistant professor of medicine and director of environmental cardiology at the Geffen School of Medicine.
To duplicate these findings in living cells, the UCLA team exposed mice with high cholesterol to the diesel particles and saw activation of some of the same gene groups in the animals’ tissue.
Exactly how air pollutants cause cardiovascular injury is poorly understood. But we do know that these particles are coated with chemicals that damage tissue and cause inflammation of the nose and lungs. Vascular inflammation in turn leads to cholesterol deposits and clogged arteries, which can give rise to blood clots that trigger heart attack or stroke.—Dr. André Nel
The researchers’ next step will be to convert the genes’ responses to the pollutant-cholesterol combination into a biomarker that will enable physicians to easily evaluate air pollution’s effect on health, especially cardiovascular disease.
The American Cancer Society has reported a 6% increase in heart- and lung-related deaths for every 10 micrograms per cubic meter rise in particulates.
The research team included investigators from the fields of nanomedicine, cardiology and human genetics and from the Southern California Particle Center. Other co-authors included Ning Li, Berenice Barajas and Aldons J. Lusis of the David Geffen School of Medicine at UCLA; Wei Zhao and Steve Horvath of the UCLA School of Public Health; Michael Kleinman of the University of California, Irvine; and Constantinos Sioutas of USC.
Grants from the National Institute of Environmental Health Sciences; the National Institute of Allergy and Infectious Diseases; the National Heart, Blood and Lung Institute; the US Environmental Protection Agency; and the Robert Wood Johnson Foundation supported the study.
“Air pollutant chemicals and oxidized lipids exhibit genome wide synergistic effects on endothelial cells”; Ke Wei Gong, Wei Zhao, Ning Li, Berenice Barajas, Michael Kleinman, Constantinos Sioutas, Steve Horvath, Aldons J Lusis, Andre E Nel and Jesus A Araujo; Genome Biology 2007, 8:R149 doi:10.1186/gb-2007-8-7-r149
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