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Background Associations between exposure to paniculate matter and susceptibility to cardiovascular events have been reported. Although the underlying mechanisms are not fully understood, this association seems to be particularly exaggerated in the presence of atherothrombotic risk factors. The present study was undertaken in low-density lipoprotein receptor knockout (LDLR/KO) mice to test the hypothesis that long-term exposure to a high dose of nano-sized carbon black (CB) exacerbates atherosclerotic lesions. Methods and Results LDLR/KO mice were subjected to a 10-week intratracheal dispersion of CB (1mg/week) or air under a 0% or 0.51% cholesterol (Chol) diet. Development of aortic lipid-rich lesions was detected in mice under a 0.51% Chol diet with or without CB dispersion, but not in mice fed a 0% Chol diet with or without CB. Quantification of the area stained with oil red O revealed the highest percentage in CB-treated mice on a 0.51% Chol diet among the 4 groups. One-way ANOVA indicated CB-treated mice with 0.51% Chol diet had a significantly higher percentage of positive staining than vehicle-treated mice with 0.51% Chol diet (p<0.05). Conclusions In LDLR-deficient mice under a high Chol diet, exposure to CB resulted in acceleration of development of atherosclerosis.