Toll-Like Receptor 9 Inactivation Alleviated Atherosclerotic Progression and Inhibited Macrophage Polarized to M1 Phenotype in ApoE−− Mice

Abstract EN

Objective.

Toll-like receptor 9 (TLR9) is involved in many inflammatory diseases, but its role in atherosclerosis remains controversial.

This study aimed to investigate the role of TLR9 in atherosclerosis development and macrophage polarization.

Methods.

ApoE−/− mice were treated with vehicle or IRS869 for 12 weeks.

Plaque vulnerability was assessed with immunohistochemical analysis, picro-sirius red, and oil red O staining.

The expressions of M1- and M2-associated markers in plaques were detected by RT-PCR and immunofluorescence.

The aorta TLR9 and its downstream molecules including myeloid differentiation protein 88 (MyD88), phosphorylated nuclear factor-kappa B (p-NF-κB), and interferon regulatory factor 7 (IRF7) were determined by western blot analysis.

The frequency of M1 and M2 subtype in RAW264.7 cells treated with IRS869 and/or ODN1826 was evaluated with flow cytometry.

Results.

In ApoE−/− mice, functional inactivation of TLR9 pathway resulted in attenuated atherosclerosis development, as manifested by reduced plaque burden and by decreased plaque vulnerability.

Mechanistically, TLR9 inhibition prevented the activation of MyD88/NF-κB pathway and shifted the balance of M1/M2 toward M2 macrophages that were involved.

Conclusions.

Our data indicated that TLR9 inactivation ameliorated atherosclerosis via skewing macrophage plasticity to M2 phenotype in ApoE-deficient mice.

These findings may provide a promising therapeutic strategy for atherosclerosis.