Project at a Glance
Project Status: complete
Title: Cardiopulmonary health effects: toxicity of semi-volatile and non-volatile components of ultrafine PM
Principal Investigator / Author(s): Kleinman, Michael T.
Contractor: UC Irvine
Contract Number: 07-307
Research Program Area: Health & Exposure
Topic Areas: Health Effects of Air Pollution, Toxic Air Contaminants
The goal of this project was to determine whether or not the toxicity of ultrafine (UFP; particles ≤ 0.18 μm aerodynamic diameter) particles depends on the concentration and composition of semi-volatile and non-volatile fractions of the PM. We tested the hypothesis that adverse effects of exposure to these UFP, which are primarily emitted by combustion sources and are highly enriched in semi-volatile components, will be significantly attenuated by removal of those components from the aerosol. We used a unique mobile in vivo rodent exposure system in combination with a particle concentrator and thermal denuder to study the cardiopulmonary effects of UFP, before and after the removal of the semi-volatile components. The study used genetically modified (apoE-/-) mice that had impaired lipid metabolism and were therefore predisposed to the development of atherosclerotic-like plaques. Exposures were 6 hr/day, 4 days per week for 8 weeks and were conducted near the University of Southern California campus in central Los Angeles. Detailed chemical and physical characterization examinations of the concentrated ambient UFP (CAPs) and thermally denuded CAPs were conducted. The thermal denuder removed more than 60% of the particle-associated organic compounds (OC) but did not remove the non-volatile components such as elemental carbon (EC) or trace metals. Exposure to undenuded CAPs accelerated the development of atherosclerotic plaque in the apoE-/- mice, characterized by decreased arterial lumen diameters and increased incorporation of lipids in arterial walls. The lumen diameters and arterial wall lipid contents in apoE-/- mice exposed to thermally denuded CAPs suggested significantly less plaque development than in the mice exposed to undenuded CAPs and were not different from plaque levels in apoE-/- exposed to purified air, as controls. In addition, heart rate variability was decreased in the mice exposed to undenuded CAPs but not in the mice exposed to either purified air or denuded CAPs. In a separate experiment apoE-/- mice were exposed to air, undenuded CAPs and the particle free organic compounds (PFO) that were stripped from the CAPs in the thermodenuder and delivered to the exposure system. This study demonstrated that the organic compounds, independent of the presence of particles, played an active role in the acceleration of plaque development. Cholesterol and low density lipoprotein-cholesterol (LDL) levels were relatively high in the apoE-/- mice, as would be expected. Exposure to undenuded CAPs, denuded CAPs and PFO all induced increased levels of both cholesterol and LDL in the serum of these mice, but only the undenuded CAPs and the PFO caused significant serum lipid peroxidation, which is a known contributor to plaque formation. We therefore conclude that the organic constituents of UFP contribute to the accelerated development of atherosclerotic plaque in arteries, lipid oxidation is an important mechanism of action in PM-induced coronary artery disease, and that removal of the organic compounds from PM greatly ameliorates plaque development associated with air pollutant exposure. These findings suggest that emission control measures that remove and sequester or destroy organic constituents of combustion generated aerosols could benefit public health because coronary artery disease is a leading contributor to heart-related deaths, which represents about 50% of deaths, annually, in California and other states as well.
For questions regarding research reports, contact: Heather Choi at (916) 322-3893
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