NAT10 Modulates Atherosclerosis Progression Mediated by Macrophage Polarization Through Regulating ac4C Modification...

Atherosclerosis (AS) is an inflammatory disease affected by macrophage polarization. N⁴-acetylcytosine (ac4C) modification mediated by N-acetyltransferase 10 (NAT10). In this study, we aimed to elucidate the role of ac4C modification mediated macrophage polarization in AS through in vivo and in vitro experiments. The ac4C level was measured using dot blot. Macrophage polarization was assessed by quantitative real-time PCR and flow cytometry. Underlying mechanism was analyzed by methylated RNA Immunoprecipitation (MeRIP), RIP and dual luciferase report. Results showed that the NAT10 expression and ac4C level were increased in patients with AS. Additionally, NAT10 knockdown promoted M1 to M2 polarization and suppressed TLR9 ac4C level. TLR9 overexpression reversed macrophage polarization regulated by NAT10 knockdown. Furthermore, M1 polarization and atherosclerosis in vivo was inhibited by NAT10 knockdown. In conclusion, we demonstrated that NAT10 regualted AS progression mediated by macrophage polarization through regulating ac4C modification of TLR9 and provided a new theoretical basis.