EXPERIMENTAL STUDY
Particulate air pollution induces progression of atherosclerosis
Tatsushi Suwa, MD, PhD*,
James C. Hogg, MD, PhD*,
Kevin B. Quinlan, BSc*,
Akira Ohgami, MD, PhD*,
Renaud Vincent, PhD and
Stephan F. van Eeden, MD, PhD*,*
* McDonald Research Laboratory and iCAPTURE Centre, University of British Columbia, St. Paul’s Hospital, Vancouver, British Columbia, Canada
Environmental Health Directorate, Health Canada, Ottawa, Ontario, Canada
Manuscript received June 25, 2001;
revised manuscript received December 3, 2001,
accepted January 2, 2002.
* Reprint requests and correspondence: Dr. Stephan F. van Eeden, McDonald Research Laboratory, University of British Columbia, St. Paul’s Hospital, 1081 Burrard Street, Vancouver, BC, Canada V6Z1Y6.
svaneeden{at}mrl.ubc.ca
OBJECTIVES: We sought to determine the effect of exposure to air pollution particulate matter <10 µm (PM10) on the progression of atherosclerosis in rabbits.
BACKGROUND: Epidemiologic studies have associated exposure to ambient PM10 with increased cardiovascular morbidity and mortality. We have previously shown that PM10 exposure induces a systemic inflammatory response that includes marrow stimulation, and we hypothesized that this response accelerates atherosclerosis.
METHODS: Watanabe heritable hyperlipidemic rabbits were exposed to PM10 (n = 10) or vehicle (n = 6) for four weeks, and bone marrow stimulation was measured. Quantitative histologic methods were used to determine the morphologic features of the atherosclerotic lesions.
RESULTS: Exposure to PM10 caused an increase in circulating polymorphonuclear leukocytes (PMN) band cell counts (day 15: 24.6 ± 3.0 vs. 11.5 ± 2.7 x 107/l [PM10 vs. vehicle], p < 0.01) and an increase in the size of the bone marrow mitotic pool of PMNs. Exposure to PM10 also caused progression of atherosclerotic lesions toward a more advanced phenotype. The volume fraction (vol/vol) of the coronary atherosclerotic lesions was increased by PM10 exposure (33.3 ± 4.6% vs. 19.5 ± 3.1% [PM10 vs. vehicle], p < 0.05). The vol/vol of atherosclerotic lesions correlated with the number of alveolar macrophages that phagocytosed PM10 (coronary arteries: r = 0.53, p < 0.05; aorta: r = 0.51, p < 0.05). Exposure to PM10 also caused an increase in plaque cell turnover and extracellular lipid pools in coronary and aortic lesions, as well as in the total amount of lipids in aortic lesions.
CONCLUSIONS: Progression of atherosclerosis and increased vulnerability to plaque rupture may underlie the relationship between particulate air pollution and excess cardiovascular death.
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Abbreviations and Acronyms
| | WHHL | | BrdU | | 5"-bromo-2"-deoxyuridine | | HDL | | high-density lipoprotein | | LAD | | left anterior descending coronary artery | | LCx | | left circumflex coronary artery | | LDL | | low-density lipoprotein | | LMCA | | left main coronary artery | | MCP-1 | | monocyte chemoattractant protein-1 | | PM10 | | particulate matter <10 µm | | PMN | | polymorphonuclear leukocyte | | RCA | | right coronary artery | | TC | | total cholesterol | | vol/vol | | volume fraction | | WHHL | | Watanabe heritable hyperlipidemic |
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