Background:
Micro- and nanoplastics (MNPs) have been detected in multiple human tissues and organs. In a recent study, the presence of MNPs in carotid artery plaques was associated with an increased risk of cardiovascular events. However, how MNP exposure causally contributes to the progression of atherosclerosis remains elusive.
Methods and Results:
ApoE−/− mice were exposed to a mixture of polystyrene MNPs (50 nm, 500 nm, and 5 μm, 1:1:1) at a dose of 10 mg/kg three times per week by oral gavage, combined with a high-fat diet for 8 weeks. MNP exposure significantly increased the area of atherosclerotic plaques (median [IQR]: 1.47 [1.10–2.18] vs. 3.50 [2.42–4.75] × 10⁵ µm²; p = 0.0411). Flow cytometry analysis revealed elevated numbers of monocytes (mean ± SD: 0.29 ± 0.20 vs. 0.67 ± 0.41 ×10⁴/aorta; p = 0.0161), macrophages (mean ± SD: 1.05 ± 0.71 vs. 2.79 ± 1.11×10⁴/aorta; p = 0.0007), and neutrophils (mean ± SD: 1.12 ± 0.40 vs. 2.89 ± 1.76 ×10³/aorta; p = 0.0099) in the aorta of MNP-treated mice, although plaque macrophage proliferation was not increased. Moreover, MNP exposure elevated the numbers of blood and splenic monocytes and neutrophils without altering their numbers in the bone marrow. RNA-seq analysis showed upregulation of Mki67 expression in the spleen after MNP treatment, suggesting enhanced extramedullary hematopoiesis. We currently explore how MNP exposure promotes extramedullary hematopoiesis.
Conclusion:
MNP exposure promotes myeloid cell proliferation in the spleen, leading to increased supply of myeloid cells and enhanced accumulation of monocytes, macrophages, and neutrophils in atherosclerotic plaques, thereby exacerbating plaque inflammation and progression. Ongoing studies are investigating the underlying immune mechanisms by which MNPs influence atherosclerosis development in mice.
