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Long-term Air Pollution Exposure and Acceleration of Atherosclerosis and Vascular Inflammation in an Animal Model
Qinghua Sun, MD, PhD;
Aixia Wang, BS;
Ximei Jin, BS;
Alex Natanzon, MD;
Damon Duquaine, MS;
Robert D. Brook, MD;
Juan-Gilberto S. Aguinaldo, MD;
Zahi A. Fayad, PhD;
Valentin Fuster, MD, PhD;
Morton Lippmann, PhD;
Lung Chi Chen, PhD;
Sanjay Rajagopalan, MD
JAMA. 2005;294:3003-3010.
Context Recent studies have suggested a link between inhaled particulate matter exposure in urban areas and susceptibility to cardiovascular events; however, the precise mechanisms remain to be determined.
Objective To test the hypothesis that subchronic exposure to environmentally relevant particulate matter, even at low concentrations, potentiates atherosclerosis and alters vasomotor tone in a susceptible disease model.
Design, Setting, and Participants Between July 21, 2004, and January 12, 2005, 28 apolipoprotein E–/– (apoE–/–) mice were, based on randomized assignments, fed with normal chow or high-fat chow and exposed to concentrated ambient particles of less than 2.5 µm (PM2.5) or filtered air (FA) in Tuxedo, NY, for 6 hours per day, 5 days per week for a total of 6 months.
Main Outcome Measures Composite atherosclerotic plaque in the thoracic and abdominal aorta and vasomotor tone changes.
Results In the high-fat chow group, the mean (SD) composite plaque area of PM2.5 vs FA was 41.5% (9.8%) vs 26.2% (8.6%), respectively (P<.001); and in the normal chow group, the composite plaque area was 19.2% (13.1%) vs 13.2% (8.1%), respectively (P = .15). Lipid content in the aortic arch measured by oil red-O staining revealed a 1.5-fold increase in mice fed the high-fat chow and exposed to PM2.5 vs FA (30.0 [8.2] vs 20.0 [7.0]; 95% confidence interval [CI], 1.21-1.83; P = .02). Vasoconstrictor responses to phenylephrine and serotonin challenge in the thoracic aorta of mice fed high-fat chow and exposed to PM2.5 were exaggerated compared with exposure to FA (mean [SE], 134.2% [5.2%] vs 100.9% [2.9%], for phenylephrine, and 156.0% [5.6%] vs 125.1% [7.5%], for serotonin; both P = .03); relaxation to the endothelium-dependent agonist acetylcholine was attenuated (mean [SE] of half-maximal dose for dilation, 8.9 [0.2] x 10-8 vs 4.3 [0.1] x 10-8, respectively; P = .04). Mice fed high-fat chow and exposed to PM2.5 demonstrated marked increases in macrophage infiltration, expression of the inducible isoform of nitric oxide synthase, increased generation of reactive oxygen species, and greater immunostaining for the protein nitration product 3-nitrotyrosine (all P<.001).
Conclusion In an apoE–/– mouse model, long-term exposure to low concentration of PM2.5 altered vasomotor tone, induced vascular inflammation, and potentiated atherosclerosis.
Author Affiliations: The Zena and Michael A. Wiener Cardiovascular Institute, Marie-Josée and Henry R. Kravis Center for Cardiovascular Health, Mount Sinai School of Medicine, New York, NY (Drs Sun, Natanzon, Aguinaldo, Fayad, Fuster, and Rajagopalan, and Ms Wang); Department of Environmental Medicine and Nelson Institute of Environmental Medicine, New York University School of Medicine, Tuxedo (Drs Lippmann and Chen, and Ms Jin); and Department of Internal Medicine, University of Michigan, Ann Arbor (Dr Brook and Mr Duquaine).
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