Diesel exhaust particulate increases the size and complexity of lesions in atherosclerotic mice

作者：Miller Mark R^*; McLean Steven G; Duffin Rodger; Lawal Akeem O; Araujo Jesus A; Shaw Catherine A; Mills Nicholas L; Donaldson Ken; Newby David E; Hadoke Patrick W F

来源：Particle and Fibre Toxicology, 2013, 10(1): 61.

DOI：10.1186/1743-8977-10-61

• Diesel
• Air pollution
• P
• Atherosclerosis
• ApoE
• Oxidative stress

Objective: Diesel exhaust particulate (DEP), a major component of urban air pollution, has been linked to atherogenesis and precipitation of myocardial infarction. We hypothesized that DEP exposure would increase and destabilise atherosclerotic lesions in apolipoprotein E deficient (ApoE(-/-)) mice.
Methods: ApoE(-/-) mice were fed a 'Western diet' (8 weeks) to induce 'complex' atherosclerotic plaques, with parallel experiments in normal chow fed wild-type mice. During the last 4 weeks of feeding, mice received twice weekly instillation (oropharyngeal aspiration) of 35 mu L DEP (1 mg/mL, SRM-2975) or vehicle (saline). Atherosclerotic burden was assessed by en-face staining of the thoracic aorta and histological examination of the brachiocephalic artery.
Results: Brachiocephalic atherosclerotic plaques were larger in ApoE(-/-) mice treated with DEP (59 +/- 10%) than in controls (32 +/- 7%; P = 0.017). In addition, DEP-treated mice had more plaques per section of artery (2.4 +/- 0.2 vs 1.8 +/- 0.2; P = 0.048) and buried fibrous layers (1.2 +/- 0.2 vs 0.4 +/- 0.1; P = 0.028). These changes were associated with lung inflammation and increased antioxidant gene expression in the liver, but not with changes in endothelial function, plasma lipids or systemic inflammation.
Conclusions: Increased atherosclerosis is caused by the particulate component of diesel exhaust producing advanced plaques with a potentially more vulnerable phenotype. These results are consistent with the suggestion that removal of the particulate component would reduce the adverse cardiovascular effects of diesel exhaust.

• 出版日期2013-12-11