Environmental Factor, December 2006, National Institute of Environmental Health Sciences
Extramural Researcher Shines at American Heart Association Meeting
By Eddy Ball
NIEHS-funded research by Jesus Araujo, M.D., Ph.D., received a Basic Science Research Award at the annual American Heart Association Scientific Sessions poster competition held November 12 - 15 in Chicago. Araujo is a cardiologist and assistant professor of medicine at the David Geffen School of Medicine at the University of California at Los Angeles. He was co-investigator for the study "Ambient Ultrafine Particulate Matter Enhances Atherosclerosis in apoE Null Animals."
According to DERT Cellular, Organ and Systems Pathobiology Branch Chief Pat Mastin, Ph.D., the research is important for its exploration of the contribution of exposure to air pollution, especially particulate matter (PM) air pollution, to cardiovascular disease. For the last 10 to 15 years, there has been growing epidemiologic evidence of an association between cardiovascular disease and PM, which is measured in microns or micrometers. One micrometer is one millionth of a meter - about 75 times smaller than the width of a human hair. These tiny particles primarily come from motor vehicle exhaust, power plant emissions and other operations that involve the burning of fossil fuels. Araujo's award-winning study added significant evidence to support the hypothesis that increased exposure to PM in polluted air increases risk of atherosclerosis and may be especially harmful when combined with additional risk factors.
Araujo's team examined the differences in the area of lesions in the ascending aorta of 62 apoE-null male mice. The investigators hypothesized that inhaled PM would act synergistically with known pro-atherogenic (cardiovascular disease promoting) stimuli and mediators. They predicted that PM, together with pro-atherogenic stimulators and mediators, would lead to a significant increase in the area of lesions due to increased oxidative stress. The team also expected that inhaled smaller particles would have a greater pro-inflammatory effect than larger ones. Test groups included non-exposed (NE) mice, animals breathing filtered air (FA), mice exposed to fine particulate matter (FP), less than 2.5 micrometers in diameter, and mice exposed to ultrafine particles (UFP), measuring less than 0.18 micrometer in diameter.
As predicted, the mice exposed to UFP over a 75-hour period developed significantly larger atherosclerotic lesions than the other groups. The area of the UFP mice lesions was nearly twice that of NE mice, over 50% greater than FA mice and 25% greater than FP mice. An in vitro analysis of human microvascular endothelial cell line confirmed that diesel exhaust UFP synergized with an oxidized LDL (the "bad" cholesterol) pro-atherogenic mediator to promote lesion development in the vascular wall. The exposure also led to the up-regulation of a large number of genes.
Araujo earned a M.Sc. degree in Immunology at the Venezuelan Institute for Scientific Research, an M.D. degree Magna Cum Laude at the Central University of Venezuela and a Ph.D. in Molecular Biology at UCLA. He completed internal medicine residency training at Beth Israel Medical Center, Albert Einstein College of Medicine in New York and a cardiology fellowship at UCLA Medical Center in Los Angeles. His research interests have focused on identifying cytoprotective genes relevant in vascular inflammatory processes such as atherosclerosis and cardiac allograft transplantation and, more recently, on dissecting the mechanisms on how air particulate matter exposure promotes atherosclerosis and ischemic heart disease. He is particularly interested in identifying prominent gene-environment links of relevance in cardiovascular pathology.
A grant from NIEHS through a joint NIEHS-EPA program, "The Role of Air Pollutants in Cardiovascular Disease," supported Araujo's research. Grantee Andre Nel, M.B.Ch.B., Ph.D., was principal investigator of the study. Nel is a practicing allergist/immunologist at UCLA and director of the Cellular Immunology Activation Laboratory in the Johnson Cancer Center at UCLA.