Acceleratory Effects of Ambient Fine Particulate Matter on the Development and Progression of Atherosclerosis in Apolipoprotein E Knockout Mice by Down-Regulating CD4+CD25+Foxp3+ Regulatory T Cells.

Objective: Atherosclerosis is an autoimmune inflammatory disease that is closely associated with long-term exposure to fine particulate matter (PM2.5). CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) play a critical role in the regulation of T cell-mediated immune responses, and the depletion of CD4(+)CD25(+)Foxp3(+) Tregs has been thought to play a prominent role in atherosclerosis. Therefore, we investigated the association between the CD4(+)CD25(+)Foxp3(+) Tregs population and atherosclerotic development in ApoE(-/-) mice exposed to PM2.5. Methods: We employed a real-world system to subject 40 ApoE(-/-) mice to ambient inhalation of PM2.5 (PM2.5 group, n= 20) or filtered air (FA group, n= 20) for 12 weeks. PM2.5 source apportionment, atherosclerotic lesions within aorta, lipid deposition and plaque accumulation in whole artery, serum level of inflammatory factors and lipid profiles, CD4(+)CD25(+)Foxp3(+) Tregs population in splenocytes, Foxp3 protein and mRNA expressions in descending aorta and spleen were quantified, respectively. Results: The daily average concentration of PM2.5 was 57.4 +/- 25.6 mu g/m(3). Atherosclerotic lesions within aorta, lipid deposition and plaque accumulation in whole artery, serum levels of IL-6, TNF-alpha, TC and LDL-C in the PM2.5 group increased significantly compared to the FA group. Whereas, serum levels of IL-10 and TGF-beta, CD4+CD25+Foxp3+ Tregs population in splenocytes, Foxp3 protein and mRNA expressions in descending aorta and spleen in the PM2.5 group decreased significantly compared to the FA group. Conclusion: These results suggest that PM2.5 could accelerate the development of atherosclerosis in ApoE(-/-) mice, which is related to CD4(+)CD25(+)Foxp3(+) Tregs down-regulation, as well as lipid deposition and systemic inflammation.