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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.

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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